314 results on '"Paul J. Fadel"'
Search Results
2. Sympathetic transduction to blood pressure during euglycemic-hyperinsulinemia in young healthy adults: role of burst amplitude
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Benjamin E. Young, Jaume Padilla, J. Kevin Shoemaker, Timothy B. Curry, Paul J. Fadel, and Jacqueline K. Limberg
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Physiology ,Physiology (medical) - Abstract
Insulin acts centrally to stimulate sympathetic vasoconstrictor outflow to skeletal muscle and peripherally to promote vasodilation. Given these divergent actions, the “net effect” of insulin on the transduction of muscle sympathetic nerve activity (MSNA) into vasoconstriction and thus, blood pressure (BP) remains unclear. We hypothesized that sympathetic transduction to BP would be attenuated during hyperinsulinemia compared with baseline. In 22 young healthy adults, MSNA (microneurography), and beat-to-beat BP (Finometer or arterial catheter) were continuously recorded, and signal-averaging was performed to quantify the mean arterial pressure (MAP) and total vascular conductance (TVC; Modelflow) responses following spontaneous bursts of MSNA at baseline and during a euglycemic-hyperinsulinemic clamp. Hyperinsulinemia significantly increased MSNA burst frequency and mean burst amplitude (baseline: 46 ± 6 au; insulin: 65 ± 16 au, P < 0.001) but did not alter MAP. The peak MAP (baseline: 3.2 ± 1.5 mmHg; insulin: 3.0 ± 1.9 mmHg, P = 0.67) and nadir TVC ( P = 0.45) responses following all MSNA bursts were not different between conditions indicating preserved sympathetic transduction. However, when MSNA bursts were segregated into quartiles based on their amplitudes at baseline and compared with similar amplitude bursts during hyperinsulinemia, the peak MAP and TVC responses were blunted (e.g., largest burst quartile: MAP, baseline: Δ4.4 ± 1.7 mmHg; hyperinsulinemia: Δ3.0 ± 0.8 mmHg, P = 0.02). Notably, ∼15% of bursts during hyperinsulinemia exceeded the size of any burst at baseline, yet the MAP/TVC responses to these larger bursts (MAP, Δ4.9 ± 1.4 mmHg) did not differ from the largest baseline bursts ( P = 0.47). These findings indicate that increases in MSNA burst amplitude contribute to the overall maintenance of sympathetic transduction during hyperinsulinemia.
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- 2023
3. Proceedings from the Albert Charitable Trust Inaugural Workshop on ‘Understanding the Acute Effects of Exercise on the Brain’
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Jill N. Barnes, Jeffrey M. Burns, Marcas M. Bamman, Sandra A. Billinger, Sue C. Bodine, Frank W. Booth, Patrice Brassard, Tameka A. Clemons, Paul J. Fadel, Paige C. Geiger, Swathi Gujral, Jacob M. Haus, Scott E. Kanoski, Benjamin F. Miller, Jill K. Morris, Kristin M.S. O’Connell, David C. Poole, Darleen A. Sandoval, J. Carson Smith, Russell H. Swerdlow, Shawn N. Whitehead, Eric D. Vidoni, and Henriette van Praag
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General Earth and Planetary Sciences ,General Environmental Science - Abstract
An inaugural workshop supported by “The Leo and Anne Albert Charitable Trust,” was held October 4–7, 2019 in Scottsdale, Arizona, to focus on the effects of exercise on the brain and to discuss how physical activity may prevent or delay the onset of aging-related neurodegenerative conditions. The Scientific Program Committee (led by Dr. Jeff Burns) assembled translational, clinical, and basic scientists who research various aspects of the effects of exercise on the body and brain, with the overall goal of gaining a better understanding as to how to delay or prevent neurodegenerative diseases. In particular, research topics included the links between cardiorespiratory fitness, the cerebrovasculature, energy metabolism, peripheral organs, and cognitive function, which are all highly relevant to understanding the effects of acute and chronic exercise on the brain. The Albert Trust workshop participants addressed these and related topics, as well as how other lifestyle interventions, such as diet, affect age-related cognitive decline associated with Alzheimer’s and other neurodegenerative diseases. This report provides a synopsis of the presentations and discussions by the participants, and a delineation of the next steps towards advancing our understanding of the effects of exercise on the aging brain.
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- 2022
4. Impact of breakthrough COVID-19 cases during the omicron wave on vascular health and cardiac autonomic function in young adults
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Rachel J. Skow, Damsara Nandadeva, Ann-Katrin Grotle, Brandi Y. Stephens, Alexis N. Wright, and Paul J. Fadel
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Adult ,Young Adult ,Vascular Stiffness ,SARS-CoV-2 ,Physiology ,Physiology (medical) ,COVID-19 ,Humans ,Female ,Hyperemia ,Pulse Wave Analysis ,Cardiology and Cardiovascular Medicine - Abstract
We and others have previously shown that COVID-19 results in vascular and autonomic impairments in young adults. However, the newest variant of COVID-19 (Omicron) appears to have less severe complications. Therefore, we investigated whether recent breakthrough infection with COVID-19 during the Omicron wave impacts cardiovascular health in young adults. We hypothesized that measures of vascular health and indices of cardiac autonomic function would be impaired in those who had the Omicron variant of COVID-19 when compared with controls who never had COVID-19. We studied 23 vaccinated adults who had COVID-19 after December 25, 2021 (Omicron; age, 23 ± 3 yr; 14 females) within 6 wk of diagnosis compared with 13 vaccinated adults who never had COVID-19 (age, 26 ± 4 yr; 7 females). Macro- and microvascular function were assessed using flow-mediated dilation (FMD) and reactive hyperemia, respectively. Arterial stiffness was determined as carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx). Heart rate (HR) variability and cardiac baroreflex sensitivity (BRS) were assessed as indices of cardiac autonomic function. FMD was not different between control (5.9 ± 2.8%) and Omicron (6.1 ± 2.3%
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- 2022
5. Impact of COVID-19 on ambulatory blood pressure in young adults: a cross-sectional analysis investigating time since diagnosis
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Damsara Nandadeva, Rachel J. Skow, Ann-Katrin Grotle, Brandi Y. Stephens, Benjamin E. Young, and Paul J. Fadel
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Young Adult ,COVID-19 Testing ,Cross-Sectional Studies ,Physiology ,Physiology (medical) ,Hypertension ,COVID-19 ,Humans ,Blood Pressure ,Blood Pressure Monitoring, Ambulatory ,Circadian Rhythm - Abstract
Previous studies have reported detrimental effects of COVID-19 on the peripheral vasculature. However, reports on blood pressure (BP) are inconsistent, and measurements are made only in the laboratory setting. To date, no studies have measured ambulatory BP. In addition, in previous studies, time since COVID-19 diagnosis among participants varied across a wide range, potentially contributing to the inconsistent BP results. Thus, we aimed to perform a comprehensive assessment of BP and BP variability using ambulatory and laboratory (brachial and central) measurements in young adults who had COVID-19. We hypothesized that ambulatory BP would be elevated post-COVID-19 and that measures of BP would be inversely related with time since diagnosis. Twenty-eight young adults who had COVID-19 [11 ± 6 (range 3-22) wk since diagnosis] and 10 controls were studied. Ambulatory daytime, nighttime, and 24-h systolic BP, diastolic BP, and mean BP were not different between the control and COVID groups (e.g., daytime systolic BP: control, 122 ± 12 mmHg; COVID, 122 ± 10 mmHg
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- 2022
6. Cardiovascular Responses to Static Handgrip Exercise and Post-Exercise Ischemia in Heart Failure with Preserved Ejection Fraction
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Kanokwan Bunsawat, Heather L. Clifton, Stephen M. Ratchford, Jennifer R. Vranish, Jeremy K. Alpenglow, Mark J. Haykowsky, Joel D. Trinity, John J. Ryan, Paul J. Fadel, and D. Walter Wray
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Physiology ,Physiology (medical) - Abstract
Exercise intolerance is a well-described characteristic of heart failure with preserved ejection fraction (HFpEF), but whether disease-related changes in autonomic function contribute to impaired cardiovascular control during exercise is not well understood. Thus, we used a combination of static handgrip exercise (HG) and post-exercise ischemia (PEI) to examine the pressor response to exercise and isolate the skeletal muscle metaboreflex, respectively. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were assessed during 2-min of static HG at 30 and 40% of maximum voluntary contraction (MVC) and subsequent PEI in sixteen patients with HFpEF and seventeen healthy, similarly aged controls. Changes in MAP were lower in patients with HFpEF compared to controls during both 30%MVC (Δ11 ± 7 vs. Δ15 ± 8 mmHg) and 40%MVC (Δ19 ± 14 vs. Δ30 ± 8 mmHg), and a similar pattern of response was evident during PEI (30%MVC: Δ8 ± 5 vs. Δ12 ± 8 mmHg; 40%MVC: Δ13 ± 10 vs. Δ18 ± 9 mmHg) (group effect: p=0.048 and p=0.020 at 30% and 40% MVC, respectively). Changes in HR, CO, and TPR did not differ between groups during HG or PEI (p>0.05). Taken together, these data suggest a reduced pressor response to static muscle contractions in patients with HFpEF compared to similarly aged controls that may be mediated, in part, by a blunted muscle metaboreflex. These findings support a disease-related dysregulation in neural cardiovascular control that may contribute to the extreme exercise intolerance present in this patient group.
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- 2023
7. Influence of Age and Estradiol on Sympathetic Nerve Activity Responses to Exercise in Women
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Megan M. Wenner, Shane J. McGinty, Paul J. Fadel, Jasdeep Kaur, Jody L. Greaney, Wanpen Vongpatanasin, and Evan L. Matthews
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Mean arterial pressure ,medicine.medical_specialty ,Sympathetic Nervous System ,Ischemia ,Physical Therapy, Sports Therapy and Rehabilitation ,Blood Pressure ,Isometric exercise ,Cardiovascular control ,Article ,Young Adult ,Internal medicine ,Medicine ,Humans ,Orthopedics and Sports Medicine ,Exercise ,Postmenopausal women ,Estradiol ,business.industry ,Sympathetic nerve activity ,Age Factors ,Estrogens ,Baroreflex ,Middle Aged ,medicine.disease ,Postmenopause ,Blood pressure ,Endocrinology ,Female ,business - Abstract
Postmenopausal women (PMW) display exaggerated increases in blood pressure (BP) during exercise, yet the mechanism(s) involved remain unclear. Moreover, research on the impact of menopausal changes in estradiol on cardiovascular control during exercise are limited. Herein, we tested the hypothesis that sympathetic responses during exercise are augmented in PMWcompared with young women (YW), and estradiol administration attenuates these responses.Muscle sympathetic nerve activity (MSNA) and mean arterial pressure (MAP) were measured in 13 PMW (58 ± 1 yr) and 17 YW (22 ± 1 yr) during 2 min of isometric handgrip. Separately, MSNA and BP responses were measured during isometric handgrip in six PMW (53 ± 1 yr) before and after 1 month of transdermal estradiol (100 μg·d-1). A period of postexercise ischemia (PEI) to isolate muscle metaboreflex activation followed all handgrip bouts.Resting MAP was similar between PMW and YW, whereas MSNA was greater in PMW (23 ± 3 vs 8 ± 1 bursts per minute; P0.05). During handgrip, the increases in MSNA (PMW Δ16 ± 2 vs YW Δ6 ± 1 bursts per minute; P0.05) and MAP (PMW Δ18 ± 2 vs YW Δ12 ± 2 mm Hg; P0.05) were greater in PMW and remained augmented during PEI. Estradiol administration decreased resting MAP but not MSNA in PMW. Moreover, MSNA (PMW (-E2) Δ27 ± 8 bursts per minute versus PMW (+E2) Δ12 ± 5 bursts per minute; P0.05) and MAP (Δ31 ± 8 mm Hg vs Δ20 ± 6 mm Hg; P0.05) responses during handgrip were attenuated in PMW after estradiol administration. Likewise, MAP responses during PEI were lower after estradiol.These data suggest that PMW exhibit an exaggerated MSNA and BP response to isometric exercise, due in part to heightened metaboreflex activation. Furthermore, estradiol administration attenuated BP and MSNA responses to exercise in PMW.
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- 2023
8. Contributors
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Daniela Accorsi–Mendonça, David J. Adams, Andrew M. Allen, Marlies Alvarenga, Jeffrey L. Ardell, Amy C. Arnold, Jesse L. Ashton, Mark B. Badrov, Brennan A. Ballantyne, Emma N. Bardsley, Soledad Barez-Lopez, Susan M. Barman, Carolyn J. Barrett, Deborah Bauer, Christopher Bell, Alona Ben-Tal, Eduardo E. Benarroch, Italo Biaggioni, Katharina Brandl, Virginia L. Brooks, Amy E. Brown, Kirsteen N. Browning, Meredith Bryarly, Livia L. Camargo, Michael Camilleri, Preston J. Campbell, Marc G. Caron, Jason R. Carter, Mark W. Chapleau, Nisha Charkoudian, Gisela Chelimsky, Thomas C. Chelimsky, Pitcha Chompoopong, Victoria E. Claydon, Gilles Clément, Victor A. Convertino, Elizabeth A. Coon, Pietro Cortelli, Stephen N. Davis, André Diedrich, Donald J. DiPette, Debra I. Diz, Marcus J. Drake, Graeme Eisenhofer, Florent Elefteriou, Fernando Elijovich, Eva-Maria Elmenhorst, Brett A. English, Murray Esler, Rosemary Esler, Paul J. Fadel, John M. Fahrenholz, Alessandra Fanciulli, John Y. Fang, Robert D. Fealey, Nathanne S. Ferreira, Renato Filogonio, Gregory D. Fink, James P. Fisher, John S. Floras, Samuel J. Fountain, Qi Fu, Marat Fudim, Raffaello Furlan, Alfredo Gamboa, Emily M. Garland, Christopher H. Gibbons, Andrew Giritharan, David S. Goldstein, Diego A. Golombék, Elise P. Gomez-Sanchez, Celso E. Gomez-Sanchez, Robert M. Graham, Guido Grassi, Ian M. Greenlund, Blair P. Grubb, Alla Guekht, Sarah-Jane Guild, Ling Guo, Vsevolod V. Gurevich, Ralf Habermann, Joseph Hadaya, Maureen K. Hahn, Peter Hanna, Luke A. Henderson, Neil Herring, Max J. Hilz, Peter Hunter, Keith Hyland, Lauren A. Hyland, Edwin Kerry Jackson, Giris Jacob, Wilfrid Jänig, Nina Japundžić-Žigon, Carrie K. Jones, Karen M. Joos, Jens Jordan, William Joyce, Xenia Kaidonis, Horacio Kaufmann, David Kaye, Abdul Mannan Khan Minhas, Joyce S. Kim, Takeya Kitta, David D. Kline, Thomas Konecny, Natalie J. Koons, Ambrish Kumar, Cheryl L. Laffer, Andre H. Lagrange, Nora Laiken, Gavin Lambert, Elisabeth Lambert, Guillaume Lamotte, Jacques W.M. Lenders, Benjamin D. Levine, Fabian Leys, Ulrich Limper, Mabelle Lin, Eduardo Listik, Reid Longmuir, David A. Low, Phillip A. Low, James M. Luther, Vaughan G. Macefield, Benedito H. Machado, Maria-Bernadette Madel, Davide Martelli, Christopher J. Mathias, Michelle L. Mauermann, Robin M. McAllen, Fiona D. McBryde, Andrew McKeon, Michael J. McKinley, Clément Menuet, Douglas F. Milam, Marion C. Mohl, Johanna M. Montgomery, Davi J.A. Moraes, Shaun F. Morrison, David Murphy, Charles D. Nichols, Piotr Niewiński, Lucy Norcliffe-Kaufmann, Luis E. Okamoto, Mahyar Osanlouy, John W. Osborn, Viktor Oubaid, Jose-Alberto Palma, Christina Pamporaki, Brian A. Parsons, David J. Paterson, Julian F.R. Paton, Amanda C. Peltier, Umberto Pensato, Sean M. Peterson, Fenna T. Phibbs, Giulia Pierangeli, Jay D. Potts, Alejandro A. Rabinstein, Mohan K. Raizada, Satish R. Raj, Casey M. Rand, Heinz Reichmann, Calum Robertson, Rose Marie Robertson, Michael B. Robinson, Mohammed Ruzieh, Paola Sandroni, Takayuki Sato, Ernesto L. Schiffrin, Markus Schlaich, Ronald Schondorf, Harold D. Schultz, Michael M. Scott, Gino Seravalle, John R. Shannon, Abu Baker Sheikh, Cyndya A. Shibao, Kalyanam Shivkumar, Kamal Shouman, Timo Siepmann, Wolfgang Singer, Elias Soltani, Virend Somers, Aadhavi Sridharan, Nadia Stefanova, Julian Stewart, Lauren E. Stiles, Kenji Sunagawa, Jens Tank, Roland D. Thijs, Jakub Tomek, Rhian M. Touyz, Jennifer A. Tracy, R. Alberto Travagli, Bradley J. Undem, Nikhil Urs, Steven Vernino, Lauro C. Vianna, Daniel E. Vigo, Margaret A. Vizzard, Amr Wahba, Waqar Waheed, Han-Jun Wang, Tobias Wang, Qin Wang, Ruihao Wang, Debra E. Weese-Mayer, Gregor K. Wenning, Wouter Wieling, Kevin W. Williams, Ursula H. Winzer-Serhan, Scott Wood, Kai Lee Yap, Naoki Yoshimura, Kirill A. Zavalin, Dmitry Zhuravlev, Daniel B. Zoccal, and Jasenka Zubcevic
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- 2023
9. Sympatho-effector transduction
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James P. Fisher, Lauro C. Vianna, and Paul J. Fadel
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- 2023
10. Impact of COVID-19 on cardiac autonomic function in healthy young adults: potential role of symptomatology and time since diagnosis
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Rachel J. Skow, Nicole A. Garza, Damsara Nandadeva, Brandi Y. Stephens, Alexis N. Wright, Ann-Katrin Grotle, Benjamin E. Young, and Paul J. Fadel
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Young Adult ,Physiology ,Heart Rate ,Physiology (medical) ,Humans ,COVID-19 ,Female ,Heart ,Blood Pressure ,Baroreflex ,Cardiology and Cardiovascular Medicine ,Autonomic Nervous System - Abstract
Emerging evidence suggests that COVID-19 may affect cardiac autonomic function; however, the limited findings in young adults with COVID-19 have been equivocal. Notably, symptomology and time since diagnosis appear to influence vascular health following COVID-19, but this has not been explored in the context of cardiac autonomic regulation. Therefore, we hypothesized that young adults who had persistent symptoms following COVID-19 would have lower heart rate variability (HRV) and cardiac baroreflex sensitivity (BRS) compared with those who had COVID-19 but were asymptomatic at testing and controls who never had COVID-19. Furthermore, we hypothesized that there would be relationships between cardiac autonomic function measures and time since diagnosis. We studied 27 adults who had COVID-19 and were either asymptomatic (ASYM
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- 2022
11. Sympathetic transduction in humans: recent advances and methodological considerations
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David M. Keller, Paul J. Fadel, Benjamin E. Young, and Jody L. Greaney
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Male ,Sympathetic Nervous System ,Physiology ,Review ,Disease ,Cardiovascular control ,Cardiovascular System ,Human health ,Sex Factors ,Physiology (medical) ,medicine ,Humans ,Muscle, Skeletal ,business.industry ,Electrodiagnosis ,Age Factors ,Hemodynamics ,Models, Cardiovascular ,Sympathetic nerve activity ,Vascular conductance ,Race Factors ,Regional Blood Flow ,Female ,medicine.symptom ,Sympathetic outflow ,Cardiology and Cardiovascular Medicine ,business ,Transduction (physiology) ,Neuroscience ,Blood Flow Velocity ,Vasoconstriction ,Muscle Contraction - Abstract
Ever since their origin more than one half-century ago, microneurographic recordings of sympathetic nerve activity have significantly advanced our understanding of the generation and regulation of central sympathetic outflow in human health and disease. For example, it is now appreciated that a myriad of disease states exhibit chronic sympathetic overactivity, a significant predictor of cardiovascular morbidity and mortality. Although microneurographic recordings allow for the direct quantification of sympathetic outflow, they alone do not provide information with respect to the ensuing sympathetically mediated vasoconstriction and blood pressure (BP) response. Therefore, the study of vascular and/or BP responses to sympathetic outflow (i.e., sympathetic transduction) has now emerged as an area of growing interest within the field of neural cardiovascular control in human health and disease. To date, studies have primarily examined sympathetic transduction under two distinct paradigms: when reflexively evoking sympatho-excitation through the induction of a laboratory stressor (i.e., sympathetic transduction during stress) and/or following spontaneous bursts of sympathetic outflow occurring under resting conditions (i.e., sympathetic transduction at rest). The purpose of this brief review is to highlight how our physiological understanding of sympathetic transduction has been advanced by these studies and to evaluate the primary analytical techniques developed to study sympathetic transduction in humans. We also discuss the framework by which the assessment of sympathetic transduction during stress reflects a fundamentally different process relative to sympathetic transduction at rest and why findings from investigations using these different techniques should be interpreted as such and not necessarily be considered one and the same.
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- 2021
12. CORP: Standardizing methodology for assessing spontaneous baroreflex control of muscle sympathetic nerve activity in humans
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Seth W. Holwerda, Jing Wang, Paul J. Fadel, Huan Yang, Jason R. Carter, and Gary L. Pierce
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Adult ,Male ,medicine.medical_specialty ,Sympathetic Nervous System ,Time Factors ,Adolescent ,Physiology ,Baroreflex ,Young Adult ,Heart Rate ,Predictive Value of Tests ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Arterial Pressure ,Muscle, Skeletal ,Aged ,Retrospective Studies ,business.industry ,Electrodiagnosis ,Arterial baroreflex ,Sympathetic nerve activity ,Reproducibility of Results ,Middle Aged ,Healthy Volunteers ,United States ,Blood pressure ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Research Article - Abstract
The use of spontaneous bursts of muscle sympathetic nerve activity (MSNA) to assess arterial baroreflex control of sympathetic nerve activity has seen increased utility in studies of both health and disease. However, methods used for analyzing spontaneous MSNA baroreflex sensitivity are highly variable across published studies. Therefore, we sought to comprehensively examine methods of producing linear regression slopes to quantify spontaneous MSNA baroreflex sensitivity in a large cohort of subjects ( n = 150) to support a standardized procedure for analysis that would allow for consistent and comparable results across laboratories. The primary results demonstrated that 1) consistency of linear regression slopes was considerably improved when the correlation coefficient was above −0.70, which is more stringent compared with commonly reported criterion of −0.50, 2) longer recording durations increased the percentage of linear regressions producing correlation coefficients above −0.70 (1 min = 15%, 2 min = 28%, 5 min = 53%, 10 min = 67%, P < 0.001) and reaching statistical significance (1 min = 40%, 2 min = 69%, 5 min = 78%, 10 min = 89%, P < 0.001), 3) correlation coefficients were improved with 3-mmHg versus 1-mmHg and 2-mmHg diastolic blood pressure (BP) bin size, and 4) linear regression slopes were reduced when the acquired BP signal was not properly aligned with the cardiac cycle triggering the burst of MSNA. In summary, these results support the use of baseline recording durations of 10 min, a correlation coefficient above −0.70 for reliable linear regressions, 3-mmHg bin size, and importance of properly time-aligning MSNA and diastolic BP. Together, these findings provide best practices for determining spontaneous MSNA baroreflex sensitivity under resting conditions for improved rigor and reproducibility of results.
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- 2021
13. Sympathetically-mediated Cutaneous Vasoconstriction Is Similar Between Non-Hispanic Black And White Individuals
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Zachary T. Martin, John D. Akins, Jeremiah C. Campbell, Brandi Y. Stephens, Paul J. Fadel, and R. Matthew Brothers
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Physical Therapy, Sports Therapy and Rehabilitation ,Orthopedics and Sports Medicine - Published
- 2022
14. Mechanisms Determining VO 2peak During Single Leg Knee‐Extension Exercise in Heart Failure with Preserved Ejection Fraction Patients: Peripheral vs. Central Phenotypes
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Rachel J. Skow, Zachary T. Martin, Damsara Nandadeva, Christopher M. Hearon, Mitchel Samels, James P. MacNamara, Mark J. Haykowsky, Benjamin D. Levine, Paul J. Fadel, and Satyam Sarma
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Genetics ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2022
15. A Potential Link Between Negative Affective Responsivity to Daily Stress and Blood Pressure Reactivity to Acute Stress in College‐Aged Adults
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Ashley M. Darling, Jacqueline Mogle, Paul J. Fadel, Erika F. Saunders, David M. Almeida, and Jody L. Greaney
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Genetics ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2022
16. Early‐Life Thymectomy Results in T‐Cell Aging and Arterial Dysfunction in Middle‐Aged Mice
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David J. Buckley, Sunita Sharma, Manoj Sabnani, Paul J. Fadel, and Daniel W. Trott
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Genetics ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2022
17. Inflammatory phenotype and T‐cell mitochondrial reactive oxygen species in young adults with major depressive disorder
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Ann‐Katrin Grotle, Ashley M. Darling, Erika F. Saunders, Paul J. Fadel, Jody L. Greaney, and Daniel W. Trott
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Genetics ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2022
18. Impact of COVID‐19 on Ambulatory Daytime and Nighttime Blood Pressure in Young Otherwise Healthy Adults
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Damsara Nandadeva, Rachel J. Skow, Brandi Y. Stephens, Ann‐Katrin Grotle, and Paul J. Fadel
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Genetics ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2022
19. Cardiac Baroreflex Sensitivity and Heart Rate Variability Following COVID‐19 in Young Adults
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Nicole A. Garza, Damsara Nandadeva, Brandi Y. Stephens, Ann‐Katrin Grotle, Rachel J. Skow, Benjamin E. Young, and Paul J. Fadel
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Genetics ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2022
20. Central and Peripheral Postexercise Blood Pressure and Vascular Responses in Young Adults with Obesity
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Philip S. Clifford, Paul J. Fadel, Elizabeth C. Lefferts, Georgios Grigoriadis, Kanokwan Bunsawat, Tracy Baynard, Melissa M Kilianek, Bo Fernhall, and Sang Ouk Wee
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Adult ,Male ,Mean arterial pressure ,medicine.medical_specialty ,Blood Pressure ,Physical Therapy, Sports Therapy and Rehabilitation ,Vasodilation ,Post-Exercise Hypotension ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Aerobic exercise ,Orthopedics and Sports Medicine ,Obesity ,Young adult ,Exercise ,Analysis of Variance ,Leg ,business.industry ,Blood Pressure Determination ,030229 sport sciences ,Blood flow ,medicine.disease ,Peripheral ,Femoral Artery ,Cross-Sectional Studies ,Blood pressure ,Regional Blood Flow ,Hypertension ,Body Composition ,Cardiology ,Female ,business - Abstract
INTRODUCTION Adults with obesity are at an increased risk of incident hypertension. Regular aerobic exercise is recommended for the prevention and treatment of hypertension, but whether young adults with obesity exhibit impaired postexercise blood pressure (BP) and vascular responses remains unclear. PURPOSE We tested the hypothesis that young adults with obesity exhibit attenuated postexercise hypotension (PEH) and postexercise peripheral vasodilation compared with young adults without obesity. METHODS Thirty-six normotensive adults without and with obesity (11 men and 7 women per group) underwent measurements of brachial and central BP, and leg blood flow (Doppler ultrasound) at baseline and at 30, 60, and 90 min after acute 1-h moderate-intensity cycling. Leg vascular conductance (LVC) was calculated as flow/mean arterial pressure. RESULTS Both groups exhibited similar brachial and central PEH (peak change from baseline, -2 and -4 mm Hg for brachial and central systolic BPs, respectively, for both groups; time effect, P < 0.05). Both groups also exhibited postexercise peripheral vasodilation, assessed via LVC (time effect, P < 0.05), but its overall magnitude was smaller in young adults with obesity (LVC change from baseline, +47% ± 37%, +29% ± 36%, and +20% ± 29%) compared with young adults without obesity (LVC change from baseline, +88% ± 58%, +59% ± 54%, and +42% ± 51%; group effect, P < 0.05). CONCLUSIONS Although obesity did not impair PEH after acute moderate-intensity exercise, young adults with obesity exhibited smaller postexercise peripheral vasodilation compared with young adults without obesity. Collectively, these findings have identified evidence for obesity-induced alterations in the peripheral vasculature after exercise.
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- 2020
21. Influence of sex on heightened vasoconstrictor mechanisms in the non‐Hispanic black population
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R. Matthew Brothers, Brandi Y. Stephens, John D. Akins, and Paul J. Fadel
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Male ,0301 basic medicine ,Cvd risk ,Population ,Ethnic group ,Disease ,Biochemistry ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Risk Factors ,Prevalence ,Genetics ,Humans ,Medicine ,education ,Molecular Biology ,education.field_of_study ,Biological variable ,Mechanism (biology) ,business.industry ,Black or African American ,030104 developmental biology ,Cardiovascular Diseases ,Vasoconstriction ,Research studies ,Female ,business ,Vascular function ,030217 neurology & neurosurgery ,Biotechnology ,Demography - Abstract
Cardiovascular disease (CVD) affects individuals of all races and ethnicities; however, its prevalence is highest in non-Hispanic black individuals (BL) relative to other populations. While previous research has provided valuable insight into elevated CVD risk in the BL population, this work has been almost exclusively conducted in men. This is alarming given that BL women suffer from CVD at an equivalent rate to BL men and each has a greater prevalence when compared to all other ethnicities, regardless of sex. The importance of investigating sex differences in mechanisms of cardiovascular function is highlighted by the National Institute of Health requiring sex to be considered as a biological variable in research studies to better our "understanding of key sex influences on health processes and outcomes." The mechanism(s) responsible for the elevated CVD risk in BL women remains unclear and is likely multifactorial. Limited studies in BL women suggest that, while impaired vasodilator capacity is involved, heightened vasoconstrictor tone and/or responsiveness may also contribute. Within this mini-review, we will discuss potential mechanisms of elevated rates of hypertension and other CVDs in BL individuals with a particular focus on young, otherwise healthy, college-aged women. To stimulate academic thought and future research, we will also discuss potential mechanisms for impaired vascular function in BL women, as well as possible divergent mechanisms between BL men and women based on either preliminary data or plausible speculation extending from findings in the existing literature. Last, we will conclude with potential future research directions aimed at better understanding the elevated risk for hypertension and CVD in BL women.
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- 2020
22. Augmented resting beat‐to‐beat blood pressure variability in young, healthy, non‐Hispanic black men
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Jing Wang, Paul J. Fadel, Jasdeep Kaur, Brandi Y. Stephens, Jennifer R. Vranish, Benjamin E. Young, Jane N. Cloud, David M. Keller, and Thales C. Barbosa
- Subjects
Adult ,Male ,medicine.medical_specialty ,Cardiac output ,Ambulatory blood pressure ,Physiology ,Rest ,Blood Pressure ,Vasodilation ,030204 cardiovascular system & hematology ,Baroreflex ,Article ,White People ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Heart Rate ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Cardiac Output ,Nutrition and Dietetics ,business.industry ,Heart ,General Medicine ,Race Factors ,Black or African American ,medicine.anatomical_structure ,Blood pressure ,Cardiovascular Diseases ,Heart Disease Risk Factors ,Hypertension ,Cardiology ,Vascular resistance ,Vascular Resistance ,medicine.symptom ,business ,Beat (music) ,030217 neurology & neurosurgery ,Vasoconstriction - Abstract
NEW FINDINGS What is the central question of this study? The prevalence of hypertension in black individuals exceeds that in other racial groups. Despite this well-known heightened risk, the underlying contributory factors remain incompletely understood. We hypothesized that young black men would exhibit augmented beat-to-beat blood pressure variability compared with white men and that black men would exhibit augmented total peripheral resistance variability. What is the main finding and its importance? We demonstrate that young, healthy black men exhibit greater resting beat-to-beat blood pressure variability compared with their white counterparts, which is accompanied by greater variability in total peripheral resistance. These swings in blood pressure over time might contribute to the enhanced cardiovascular risk profile in black individuals. ABSTRACT The prevalence of hypertension in black (BL) individuals exceeds that in other racial groups. Recently, resting beat-to-beat blood pressure (BP) variability has been shown to predict cardiovascular risk and detect target organ damage better than ambulatory BP monitoring. Given the heightened risk in BL individuals, we hypothesized young BL men would exhibit augmented beat-to-beat BP variability compared with white (WH) men. Furthermore, given studies reporting reduced vasodilatation and augmented vasoconstriction in BL individuals, we hypothesized that BL men would exhibit augmented variability in total peripheral resistance (TPR). In 45 normotensive men (24 BL), beat-to-beat BP (Finometer) was measured during 10-20 min of quiet rest. Cardiac output and TPR were estimated (Modelflow method). Despite similar resting BP, BL men exhibited greater BP standard deviation (e.g. systolic BP SD; BL, 7.1 ± 2.2 mmHg; WH, 5.4 ± 1.5 mmHg; P = 0.006) compared with WH men, which was accompanied by a greater TPR SD (P = 0.003), but not cardiac output SD (P = 0.390). Other traditional measures of variability provided similar results. Histogram analysis indicated that BL men exhibited a greater percentage of cardiac cycles with BPs higher (> +10 mmHg higher) and lower (< -8 mmHg lower) than mean systolic BP compared with WH men (interaction, P
- Published
- 2020
23. Chronic Elevation of Endothelin-1 Alone May Not Be Sufficient to Impair Endothelium-Dependent Relaxation
- Author
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Ernesto L. Schiffrin, Scott Brown, Paul J. Fadel, Kevin F. Staveley-O’Carroll, Thomas J. Jurrissen, Ryan J Pettit-Mee, Makenzie L Woodford, Thaysa Ghiarone, Pierre Paradis, Jaume Padilla, Lauren K. Park, Shawn B. Bender, Zachary I. Grunewald, Luis A. Martinez-Lemus, Mariana Morales-Quinones, Annayya R. Aroor, James R. Ball, and Francisco I. Ramirez-Perez
- Subjects
medicine.medical_specialty ,Blotting, Western ,Disease ,In Vitro Techniques ,030204 cardiovascular system & hematology ,Endothelium dependent ,Nitric Oxide ,Sensitivity and Specificity ,Mass Spectrometry ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine.artery ,Internal medicine ,No synthase ,Internal Medicine ,medicine ,Animals ,Vasoconstrictor Agents ,Vasoconstrictor peptide ,Aorta ,Endothelin-1 ,Relaxation (psychology) ,business.industry ,Endothelial Cells ,Endothelin 1 ,Mice, Inbred C57BL ,Vasodilation ,Blood pressure ,Endocrinology ,Models, Animal ,Female ,business ,030217 neurology & neurosurgery - Abstract
Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide considered to be causally implicated in hypertension and the development of cardiovascular disease. Increased ET-1 is commonly associated with reduced NO bioavailability and impaired vascular function; however, whether chronic elevation of ET-1 directly impairs endothelium-dependent relaxation (EDR) remains elusive. Herein, we report that (1) prolonged ET-1 exposure (ie, 48 hours) of naive mouse aortas or cultured endothelial cells did not impair EDR or reduce eNOS (endothelial NO synthase) activity, respectively (P>0.05); (2) mice with endothelial cell–specific ET-1 overexpression did not exhibit impaired EDR or reduced eNOS activity (P>0.05); (3) chronic (8 weeks) pharmacological blockade of ET-1 receptors in obese/hyperlipidemic mice did not improve aortic EDR or increase eNOS activity (P>0.05); and (4) vascular and plasma ET-1 did not inversely correlate with EDR in resistance arteries isolated from human subjects with a wide range of ET-1 levels (r=0.0037 and r=−0.1258, respectively). Furthermore, we report that prolonged ET-1 exposure downregulated vascular UCP-1 (uncoupling protein-1;P
- Published
- 2019
24. Racial disparities in cardiovascular disease risk: mechanisms of vascular dysfunction
- Author
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R. Matthew Brothers, Paul J. Fadel, and David M. Keller
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Vasodilation ,Review ,Disease ,Nitric Oxide ,Risk Assessment ,Sex Factors ,Risk Factors ,Physiology (medical) ,Internal medicine ,Prevalence ,medicine ,Humans ,African american ,business.industry ,Health Status Disparities ,Cerebral Arteries ,United States ,Black or African American ,Oxidative Stress ,Cardiovascular Diseases ,Vasoconstriction ,Cardiology ,Disease risk ,Blood Vessels ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Vascular function - Abstract
Cardiovascular disease (CVD) accounts for a third of all deaths in the United States making it the leading cause of morbidity and mortality. Although CVD affects individuals of all races/ethnicities, the prevalence of CVD is highest in non-Hispanic black (BL) individuals relative to other populations. The mechanism(s) responsible for elevated CVD risk in the BL population remains incompletely understood. However, impaired vascular vasodilator capacity and exaggerated vascular vasoconstrictor responsiveness are likely contributing factors, both of which are present even in young, otherwise healthy BL individuals. Within this review, we highlight some historical and recent data, collected from our laboratories, of impaired vascular function, in terms of reduced vasodilator capacity and heightened vasoconstrictor responsiveness, in the peripheral and cerebral circulations in BL individuals. We provide data that such impairments may be related to elevated oxidative stress and subsequent reduction in nitric oxide bioavailability. In addition, divergent mechanisms of impaired vasodilatory capacity between BL men and women are discussed. Finally, we propose several directions where future research is needed to fill in knowledge gaps, which will allow for better understanding of the mechanisms contributing to impaired vascular function in this population. Ultimately, this information will allow for better lifestyle and therapeutic approaches to be implemented in an effort to minimize the increased CVD burden in the BL population.
- Published
- 2019
25. Effect of acute high-phosphate intake on muscle metaboreflex activation and vascular function
- Author
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Jennifer R. Vranish, Scott A. Smith, Jasdeep Kaur, Paul J. Fadel, Thales C. Barbosa, Brandi Y. Stephens, and Jeanette K. Blankenship
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,Brachial Artery ,Physiology ,Isometric exercise ,030204 cardiovascular system & hematology ,Phosphates ,Beverages ,Young Adult ,03 medical and health sciences ,Vascular Stiffness ,0302 clinical medicine ,High phosphate ,Physiology (medical) ,Internal medicine ,medicine.artery ,Reflex ,medicine ,Humans ,Arterial Pressure ,Brachial artery ,Muscle, Skeletal ,Reactive hyperemia ,Pulse wave velocity ,business.industry ,medicine.disease ,Adaptation, Physiological ,Chemoreceptor Cells ,Healthy Volunteers ,Blood pressure ,Regional Blood Flow ,Cardiology ,Arterial stiffness ,Phosphorus, Dietary ,Endothelium, Vascular ,Energy Metabolism ,Cardiology and Cardiovascular Medicine ,Vascular function ,business ,030217 neurology & neurosurgery ,Muscle Contraction - Abstract
Increased consumption of inorganic phosphate (Pi), an abundant ingredient in processed foods, has been associated with elevated cardiovascular disease risk; however, studies investigating underlying mechanisms are limited. Recently, high dietary Pi was shown to exaggerate the pressor response to static muscle contraction in rodents in part because of overactivation of metabolically sensitive skeletal muscle afferents. Whether acute high Pi consumption affects muscle metaboreflex activation in humans remains unknown. Furthermore, although acute high Pi consumption has been shown to impair vascular function in young healthy men, equivocal results have been reported. Therefore, we hypothesized that acute high Pi consumption augments mean arterial pressure (MAP) responses during muscle metaboreflex activation, impairs endothelial function, and increases arterial stiffness in young healthy men. Subjects performed 35% maximal voluntary contraction static handgrip (HG), followed by postexercise ischemia (PEI) to isolate muscle metaboreflex activation. Resting flow-mediated dilation (FMD) and arterial stiffness were assessed. Measures were made before (pre) and 60 min after (post) subjects consumed either a high-phosphate drink (2,000 mg phosphorus and 1,520 mg sodium) or a sodium drink (1,520 mg sodium; control). MAP responses during HG (preΔ = +23 ± 3 mmHg; postΔ = +21 ± 2 mmHg; P = 0.101) and PEI (preΔ = +21 ± 4 mmHg; postΔ = +18 ± 3 mmHg; P = 0.184) were similar before and after Pi consumption. In contrast, FMD was significantly attenuated following Pi (pre = 5.1 ± 0.5%; post = 3.5 ± 0.5%; P = 0.010), whereas arterial stiffness remained unchanged. There were no changes in any measured variable after control drink consumption. In summary, although the muscle metaboreflex remains unaffected following acute high Pi consumption in young healthy men, endothelial function is impaired. NEW & NOTEWORTHY This study was the first to investigate the influence of acute high-phosphate consumption on the pressor response during isometric handgrip and isolated muscle metaboreflex activation during postexercise ischemia in young healthy humans. We demonstrated that a single high dose of phosphate (2,000 mg) did not augment blood pressure in response to exercise or isolated muscle metaboreflex activation, but endothelial function was blunted in young healthy men.
- Published
- 2019
26. Sympathetic Transduction in Type 2 Diabetes Mellitus
- Author
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Jennifer R. Vranish, Seth W. Holwerda, David M. Keller, Paul J. Fadel, and Benjamin E. Young
- Subjects
medicine.medical_specialty ,endocrine system diseases ,business.industry ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,030204 cardiovascular system & hematology ,medicine.disease ,03 medical and health sciences ,Transduction (genetics) ,0302 clinical medicine ,Endocrinology ,Blood pressure ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Vasoconstriction - Abstract
Approximately 60% of patients with type 2 diabetes mellitus (T2D) develop hypertension. Recent work also indicates greater blood pressure (BP) excursions throughout the day in T2D. Collectively, these findings suggest altered BP control in T2D. Although muscle sympathetic nerve activity (MSNA) recordings in T2D have provided equivocal results, quantification of MSNA alone does not account for ensuing vasoconstriction and BP responses elicited by MSNA. Thus, we tested the hypothesis that patients with T2D exhibit enhanced sympathetic transduction to BP. MSNA (microneurography) and beat-to-beat BP (Finometer) were measured at rest in 21 T2D and 13 age-matched and body mass index–matched control subjects and, signal-averaging was performed to quantify the mean arterial pressure and total vascular conductance responses to spontaneous bursts of MSNA. The peak mean arterial pressure and total vascular conductance responses to spontaneous MSNA were similar between T2D and control (both P >0.05). However, further analysis, separating T2D into those taking statins (n=13, T2D +statin) and not taking statins (n=8, T2D −statin), indicated that T2D −statin patients (4.2±0.6 mm Hg) exhibited greater peak mean arterial pressure responses compared with both T2D +statin patients (2.5±0.3 mm Hg, P =0.01) and control (control: 2.8±0.3 mm Hg, P =0.02). Likewise, nadir total vascular conductance responses to spontaneous MSNA bursts were greater in T2D −statin patients (T2D −statin: −3.3±0.6 mL/(min·mm Hg), T2D +statin: −1.6±0.3 mL/(min·mm Hg), P =0.03; control −2.2±0.3 mL/(min·mm Hg), P =0.08). Notably, T2D +statin patients exhibited similar peak mean arterial pressure and total vascular conductance responses to MSNA compared with control. Collectively, these findings demonstrate, for the first time, that patients with T2D exhibit augmented sympathetic transduction and this effect seems to be offset by statin therapy.
- Published
- 2019
27. Elevated Muscle Sympathetic Nerve Activity Contributes to Central Artery Stiffness in Young and Middle-Age/Older Adults
- Author
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Seth W. Holwerda, Nealy A. Wooldridge, Gary L. Pierce, Amy K. Stroud, Francois M. Abboud, Paul J. Fadel, Michael T. Collins, Rachel E. Luehrs, and Lyndsey E. DuBose
- Subjects
Adult ,Male ,Aging ,medicine.medical_specialty ,Sympathetic Nervous System ,Vascular smooth muscle ,Brachial Artery ,030204 cardiovascular system & hematology ,Muscle, Smooth, Vascular ,Young Adult ,03 medical and health sciences ,Vascular Stiffness ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,Humans ,Medicine ,Central Artery ,Arterial Pressure ,Pulse wave velocity ,Aorta ,Aged ,business.industry ,Middle Aged ,Tone (literature) ,Middle age ,Peripheral ,Femoral Artery ,Compliance (physiology) ,Carotid Arteries ,Blood pressure ,cardiovascular system ,Cardiology ,business ,030217 neurology & neurosurgery - Abstract
Muscle sympathetic nerve activity (MSNA) influences the mechanical properties (ie, vascular smooth muscle tone and stiffness) of peripheral arteries, but it remains controversial whether MSNA contributes to stiffness of central arteries, such as the aorta and carotids. We examined whether elevated MSNA (age-related) would be independently associated with greater stiffness of central (carotid-femoral pulse wave velocity [PWV]) and peripheral (carotid-brachial PWV) arteries, in addition to lower carotid compliance coefficient, in healthy men and women (n=88, age: 19–73 years, 52% men). We also examined whether acute elevations in MSNA without increases in mean arterial pressure using graded levels of lower body negative pressure would augment central and peripheral artery stiffness in young (n=15, 60% men) and middle-age/older (MA/O, n=14, 43% men) adults. Resting MSNA burst frequency (bursts·min −1 ) was significantly correlated with carotid-femoral PWV ( R =0.44, P R =0.32, P =0.004), and carotid compliance coefficient ( R =0.28, P =0.01) after controlling for sex, mean arterial pressure, heart rate, and waist-to-hip ratio (central obesity), but these correlations were abolished after further controlling for age (all P >0.05). In young and MA/O adults, MSNA was elevated during lower body negative pressure ( P −1 , P =0.53) and carotid-brachial PWV (young: Δ+0.7±0.3 versus MA/O: Δ+0.7±0.5 m·s −1 , P =0.92), whereas carotid compliance coefficient during lower body negative pressure was significantly reduced in young but not MA/O (young: Δ−0.04±0.01 versus MA/O: Δ0.001±0.008 mm 2 ·mm Hg −1 , P
- Published
- 2019
28. Arterial Baroreflex Resetting During Exercise in Humans: Underlying Signaling Mechanisms
- Author
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Paul J. Fadel, Peter B. Raven, and Benjamin E. Young
- Subjects
Central Nervous System ,genetic structures ,Blood Pressure ,Physical Therapy, Sports Therapy and Rehabilitation ,03 medical and health sciences ,0302 clinical medicine ,Solitary Nucleus ,otorhinolaryngologic diseases ,Animals ,Humans ,Medicine ,Orthopedics and Sports Medicine ,Exercise physiology ,Exercise ,Neurons ,business.industry ,musculoskeletal, neural, and ocular physiology ,Arterial baroreflex ,030229 sport sciences ,Baroreflex ,Blood pressure ,nervous system ,Reflex ,Reactive Oxygen Species ,business ,Neuroscience ,psychological phenomena and processes ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
The arterial baroreflex (ABR) resets during exercise in an intensity-dependent manner to operate around a higher blood pressure with maintained sensitivity. This review provides a historical perspective of ABR resetting and the involvement of other neural reflexes in mediating exercise resetting. Furthermore, we discuss potential underlying signaling mechanisms that may contribute to exercise ABR resetting in physiological and pathophysiological conditions.
- Published
- 2019
29. Impact of Family History of Hypertension on Racial Differences in Flow‐Mediated Dilation and Reactive Hyperemia
- Author
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Brandi Y. Stephens, Damsara Nandadeva, Thales C. Barbosa, Paul J. Fadel, Ann-Katrin Grotle, Jasdeep Kaur, and Benjamin Young
- Subjects
medicine.medical_specialty ,business.industry ,Flow mediated dilation ,Biochemistry ,Internal medicine ,Genetics ,Cardiology ,Medicine ,Racial differences ,Family history ,business ,Molecular Biology ,Reactive hyperemia ,Biotechnology - Published
- 2021
30. Influence of Family History of Hypertension on Spontaneous Cardiac Baroreflex Sensitivity in Young Non‐Hispanic Black and White Men
- Author
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Brandi Y. Stephens, Damsara Nandadeva, Ann-Katrin Grotle, Paul J. Fadel, and Benjamin Young
- Subjects
medicine.medical_specialty ,White (horse) ,Cardiac baroreflex ,business.industry ,Biochemistry ,Internal medicine ,Genetics ,medicine ,Cardiology ,Sensitivity (control systems) ,Family history ,business ,Molecular Biology ,Biotechnology - Published
- 2021
31. Sympathetic Transduction During Euglycemic‐Hyperinsulinemia in Humans
- Author
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Paul J. Fadel, Jaume Padilla, Blair T. Johnson, Timothy B. Curry, Jacqueline K. Limberg, and Benjamin Young
- Subjects
Transduction (genetics) ,Genetics ,Hyperinsulinemia ,medicine ,Biology ,medicine.disease ,Molecular Biology ,Biochemistry ,Biotechnology ,Cell biology - Published
- 2021
32. Influence of Family History of Hypertension on Muscle Metaboreflex Activation in Young Healthy Non‐Hispanic White and Black Men
- Author
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Brandi Y. Stephens, Damsara Nandadeva, Thales C. Barbosa, Paul J. Fadel, Jennifer R. Vranish, Benjamin Young, and Jasdeep Kaur
- Subjects
White (horse) ,business.industry ,Genetics ,Medicine ,Family history ,business ,Molecular Biology ,Biochemistry ,Biotechnology ,Demography - Published
- 2021
33. Reduced resting beat‐to‐beat blood pressure variability in multiple sclerosis
- Author
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Mu Huang, Paul J. Fadel, Ben Young, Scott L. Davis, Dustin R. Allen, and Claire E. Trotter
- Subjects
medicine.medical_specialty ,business.industry ,Multiple sclerosis ,medicine.disease ,Biochemistry ,Blood pressure ,Internal medicine ,Genetics ,Cardiology ,Medicine ,business ,Molecular Biology ,Beat (music) ,Biotechnology - Published
- 2021
34. Reproducibility of the neurocardiovascular responses to common laboratory-based sympathoexcitatory stimuli in young adults
- Author
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Paul J. Fadel, Jing Wang, Zachary S. Lichter, Jody L. Greaney, Lacy M. Alexander, Lauro C. Vianna, and Gabrielle A. Dillon
- Subjects
medicine.medical_specialty ,Sympathetic Nervous System ,Physiology ,Ischemia ,Blood Pressure ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Heart Rate ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Young adult ,Muscle, Skeletal ,Reproducibility ,Hand Strength ,business.industry ,Cold pressor test ,Sympathetic nerve activity ,Reproducibility of Results ,Microneurography ,medicine.disease ,Blood pressure ,Cardiology ,business ,Laboratories ,030217 neurology & neurosurgery ,Research Article - Abstract
The magnitude of blood pressure (BP) and muscle sympathetic nerve activity (MSNA) responses to laboratory stressors is commonly used to compare neurocardiovascular responsiveness between groups and conditions. However, no studies have rigorously examined the reproducibility of BP and MSNA responsiveness. Here, we assess the within-visit reproducibility of BP (finger photoplethysmography) and MSNA (microneurography) responses to isometric handgrip (HG) and postexercise ischemia (PEI) in young healthy adults (n = 30). In a subset (n = 21), we also examined the between-visit reproducibility of responsiveness to HG, PEI, and the cold pressor test (CPT). Intraclass correlation coefficients (ICCs) were used as a primary reproducibility measure (e.g., ICC >0.75 is considered very good). Within a visit, the increase in mean arterial pressure during HG [ICC = 0.85 (0.69–0.93); P < 0.001] and PEI [ICC = 0.85 (0.69–0.93); P < 0.001] demonstrated very good reproducibility. Furthermore, the between-visit reproducibility of the pressor response to HG [ICC = 0.85 (0.62–0.94); P < 0.001], PEI [ICC = 0.84 (CI = 0.58–0.94); P < 0.001], and the CPT [ICC = 0.89 (0.72–0.95) P < 0.001]) were also very good. However, there was greater variability in both the within- [HG: ICC = 0.58 (−0.22–0.85), P = 0.001; PEI: ICC = 0.33 (−0.24–0.69), P = 0.042] and between-visit reproducibility of MSNA responsiveness [HG: ICC = 0.87 (0.53–0.96), P = 0.001; PEI: ICC = 0.24 (−0.62–0.78), P = 0.27; CPT: ICC = 0.77 (0.29–0.93), P = 0.007]. The magnitude of the BP response to several standard laboratory stimuli was very good, whereas the variability of the MSNA response to these perturbations was generally less consistent, particularly during PEI. These data provide novel insight for both study design and data interpretation when comparing neurocardiovascular responsiveness between different conditions, groups, or studies, as well as before and after interventions/treatments. NEW & NOTEWORTHY The magnitude of the increases in blood pressure and muscle sympathetic nerve activity in response to sympathoexcitatory stimuli such as static handgrip, postexercise ischemia, and the cold pressor test are commonly used to assess neurocardiovascular responsiveness. However, limited studies have comprehensively examined the reproducibility of these responses. We demonstrate that the reproducibility of the pressor response to these perturbations was very good within an individual, whereas the reproducibility of the MSNA response was less consistent.
- Published
- 2020
35. Functional sympatholysis is preserved in healthy young Black men during rhythmic handgrip exercise
- Author
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Thales C. Barbosa, Paul J. Fadel, Jasdeep Kaur, Damsara Nandadeva, Benjamin E. Young, David M. Keller, and Brandi Y. Stephens
- Subjects
Adult ,Male ,medicine.medical_specialty ,Sympathetic Nervous System ,Physiology ,common ,030204 cardiovascular system & hematology ,Caucasian American ,03 medical and health sciences ,FEV1/FVC ratio ,0302 clinical medicine ,Rhythm ,Oxygen Consumption ,Forearm ,Physiology (medical) ,Internal medicine ,medicine ,Handgrip exercise ,Humans ,Muscle, Skeletal ,Exercise ,African american ,Hand Strength ,business.industry ,Vascular conductance ,body regions ,medicine.anatomical_structure ,Regional Blood Flow ,Vasoconstriction ,common.group ,Forearm blood flow ,Cardiology ,business ,030217 neurology & neurosurgery ,circulatory and respiratory physiology ,Muscle Contraction ,Research Article - Abstract
Black men have attenuated increases in forearm vascular conductance (FVC) and forearm blood flow (FBF) during moderate- and high-intensity rhythmic handgrip exercise compared with White men, but the underlying mechanisms are unclear. Here, we tested for the first time the hypothesis that functional sympatholysis (i.e., attenuation of sympathetic vasoconstriction in the exercising muscles) is impaired in Black men compared with White men. Thirteen White and 14 Black healthy young men were studied. FBF (duplex Doppler ultrasound) and mean arterial pressure (MAP; Finometer) were measured at rest and during rhythmic handgrip exercise at 30% maximal voluntary contraction. FVC was calculated as FBF/MAP. Sympathetic activation was induced via lower body negative pressure (LBNP) at −20 Torr for 2 min at rest and from the 3rd to the 5th min of handgrip. Sympathetic vasoconstriction was assessed as percent reductions in FVC during LBNP. The groups presented similar resting FVC, FBF, and MAP. During LBNP at rest, reductions in FVC were not different between White (−35 ± 10%) and Black men (−32 ± 14%, P = 0.616), indicating similar reflex-induced sympathetic vasoconstriction. During handgrip exercise, there were minimal reductions in FVC with LBNP in either group (White: −1 ± 7%; Black: +1 ± 8%; P = 0.523), indicating functional sympatholysis in both groups. Thus, contrary to our hypothesis, our findings indicate a preserved functional sympatholysis in healthy young Black men compared with White men, suggesting that this mechanism does not appear to contribute to reduced exercise hyperemia during moderate-intensity rhythmic handgrip in this population.
- Published
- 2020
36. Sex differences in the mechanisms mediating blunted cutaneous microvascular function in young black men and women
- Author
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Jordan C. Patik, Bryon M. Curtis, Aida Nasirian, Jennifer R. Vranish, Paul J. Fadel, and R. Matthew Brothers
- Subjects
Adult ,Male ,0301 basic medicine ,Xanthine Oxidase ,medicine.medical_specialty ,Physiology ,Microdialysis ,Vasodilation ,030204 cardiovascular system & hematology ,Administration, Cutaneous ,White People ,Nitric oxide ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,Sex Factors ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,Humans ,Medicine ,Enzyme Inhibitors ,Xanthine oxidase ,Skin ,NADPH oxidase ,biology ,business.industry ,Microcirculation ,NADPH Oxidases ,Hyperthermia, Induced ,Texas ,Black or African American ,030104 developmental biology ,Endocrinology ,chemistry ,Regional Blood Flow ,Microvessels ,biology.protein ,Female ,Nitric Oxide Synthase ,Cardiology and Cardiovascular Medicine ,business ,Function (biology) - Abstract
The black population exhibits attenuated vasodilatory function across their lifespan, yet little is known regarding the mechanisms of this impairment. Recent evidence suggests a potential role for oxidative stress. Therefore, we tested the hypothesis that NADPH oxidase (NOX) and/or xanthine oxidase (XO) contribute to blunted nitric oxide (NO)-mediated cutaneous microvascular function in young black adults. In 30 white and black subjects (8 men and 7 women in each group), local heating was performed while NOX and XO were inhibited by apocynin and allopurinol, respectively, via intradermal microdialysis. The plateau in cutaneous vascular conductance (red blood cell flux/mean arterial pressure) during 39°C local heating at each site was compared with a control site perfused with lactated Ringer solution. Subsequent inhibition of NO synthase via Nω-nitro-l-arginine methyl ester allowed for quantification of the NO contribution to vasodilation during heating. Black individuals, relative to white individuals, had a blunted cutaneous vascular conductance plateau at the control site (45 ± 9 vs. 68 ± 13%max, P < 0.001) that was increased by both apocynin (61 ± 15%max, P < 0.001) and allopurinol (58 ± 17%max, P = 0.005). Black men and black women had similar responses to heating at the control site ( P = 0.99), yet apocynin and allopurinol increased this response only in black men (both P < 0.001 vs. control). The NO contribution was also increased via apocynin and allopurinol exclusively in black men. These findings suggest that cutaneous microvascular function is reduced because of NOX and XO activity in black men but not black women, identifying a novel sex difference in the mechanisms that contribute to blunted vascular responses in the black population. NEW & NOTEWORTHY We demonstrate that cutaneous microvascular responses to local heating are consistently reduced in otherwise healthy young black men and women relative to their white counterparts. Inhibition of NADPH oxidase and xanthine oxidase via apocynin and allopurinol, respectively, augments microvascular function in black men but not black women. These data reveal clear sex differences in the mechanisms underlying the racial disparity in cutaneous microvascular function.
- Published
- 2018
37. Assessment of resistance vessel function in human skeletal muscle: guidelines for experimental design, Doppler ultrasound, and pharmacology
- Author
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D. Walter Wray, Ylva Hellsten, Paul J. Fadel, Michael J. Joyner, Wayne T. Nicholson, Darren P. Casey, Daniel J. Green, Joel D. Trinity, Jacqueline K. Limberg, Michael E. Tschakovsky, and Jaume Padilla
- Subjects
Resistance vessel ,Physiology ,business.industry ,Skeletal muscle ,Cardiovascular Agents ,Ultrasonography, Doppler ,Blood flow ,Review ,medicine.anatomical_structure ,Research Design ,Physiology (medical) ,cardiovascular system ,medicine ,Humans ,Vascular Resistance ,Doppler ultrasound ,Duplex doppler ultrasound ,Cardiology and Cardiovascular Medicine ,Vascular function ,business ,Muscle, Skeletal ,Biomedical engineering - Abstract
The introduction of duplex Doppler ultrasound almost half a century ago signified a revolutionary advance in the ability to assess limb blood flow in humans. It is now widely used to assess blood flow under a variety of experimental conditions to study skeletal muscle resistance vessel function. Despite its pervasive adoption, there is substantial variability between studies in relation to experimental protocols, procedures for data analysis, and interpretation of findings. This guideline results from a collegial discussion among physiologists and pharmacologists, with the goal of providing general as well as specific recommendations regarding the conduct of human studies involving Doppler ultrasound-based measures of resistance vessel function in skeletal muscle. Indeed, the focus is on methods used to assess resistance vessel function and not upstream conduit artery function (i.e., macrovasculature), which has been expertly reviewed elsewhere. In particular, we address topics related to experimental design, data collection, and signal processing as well as review common procedures used to assess resistance vessel function, including postocclusive reactive hyperemia, passive limb movement, acute single limb exercise, and pharmacological interventions. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/guidelines-for-doppler-ultrasound-and-resistance-vessel-function/ .
- Published
- 2019
38. Water drinking enhances the gain of arterial baroreflex control of muscle sympathetic nerve activity in healthy young humans
- Author
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Igor A. Fernandes, Paul J. Fadel, Daniel Godoy Martinez, André L. Teixeira, Lauro C. Vianna, Bruno M. Silva, and Antonio C. L. Nóbrega
- Subjects
Adult ,Male ,medicine.medical_specialty ,Sympathetic Nervous System ,medicine.medical_treatment ,Musculoskeletal Physiological Phenomena ,Blood Pressure ,030204 cardiovascular system & hematology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Heart Rate ,Internal medicine ,Heart rate ,medicine ,Humans ,Ingestion ,Arterial Pressure ,Young adult ,Muscle, Skeletal ,Saline ,Osmoreceptor ,Water drinking ,business.industry ,Drinking Water ,Arterial baroreflex ,Arteries ,General Medicine ,Baroreflex ,Blood pressure ,Cardiology ,business ,030217 neurology & neurosurgery - Abstract
NEW FINDINGS What is the central question of this study? Water drinking increases muscle sympathetic nerve activity (MSNA), and it increases arterial blood pressure (ABP) in older populations but not in young healthy subjects. Does an increase in gain of arterial baroreflex control of MSNA contribute to maintenance of ABP after water drinking in healthy young subjects? What is the main finding and its importance? The gain of arterial baroreflex control of MSNA was increased and remained elevated 60 min after water drinking (500 ml) but remained unchanged after saline intake. An enhancement in gain of arterial baroreflex control of MSNA contributes to the maintenance of ABP after water drinking in young healthy subjects, probably via osmosensitive mechanisms. ABSTRACT Water drinking increases muscle sympathetic nerve activity (MSNA), which is accompanied by a profound pressor response in patients with impaired arterial baroreflex function and in older populations, but not in healthy young subjects. We tested the hypothesis that an enhancement in the gain of arterial baroreflex control of MSNA contributes to the maintenance of arterial blood pressure after water drinking in healthy young subjects. The MSNA, arterial blood pressure and heart rate were measured in 10 healthy men (24 ± 2 years old; mean ± SD) before and for 60 min after ingestion of 500 ml of bottled water or saline solution. Weighted linear regression analysis between MSNA and diastolic blood pressure was used to determine the gain (i.e. sensitivity) of arterial baroreflex control of MSNA. After water drinking, MSNA was significantly elevated within 15 min and remained above baseline for up to 60 min [e.g. 21 ± 10 bursts (100 heart beats)-1 mmHg-1 at baseline versus 35 ± 14 bursts (100 heart beats)-1 mmHg-1 at 30 min; P < 0.01], whereas mean arterial blood pressure (e.g. 87 ± 7 mmHg at baseline versus 89 ± 7 mmHg at 30 min; P = 0.34) and heart rate were unchanged. The arterial baroreflex-MSNA gain for bursts incidence was increased and remained elevated throughout the protocol [e.g. -2.25 ± 0.99 bursts (100 heart beats)-1 mmHg-1 at baseline versus -4.32 ± 1.53 bursts (100 heart beats)-1 mmHg-1 at 30 min; P < 0.01]. Importantly, saline intake had no effect on arterial baroreflex-MSNA gain or any neurocardiovascular variables. These findings demonstrate that water drinking enhances the gain of arterial baroreflex control of MSNA in healthy young men, which may contribute to buffering the pressor response after water drinking, probably via osmosensitive mechanisms.
- Published
- 2018
39. Brief periods of inactivity reduce leg microvascular, but not macrovascular, function in healthy young men
- Author
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Paul J. Fadel, Jennifer R. Vranish, Jaume Padilla, Benjamin E. Young, Brandi Y. Stephens, and Jasdeep Kaur
- Subjects
Adult ,Male ,medicine.medical_specialty ,Supine position ,Brachial Artery ,Posture ,Hyperemia ,Vasodilation ,Motor Activity ,030204 cardiovascular system & hematology ,Sitting ,Microcirculation ,Young Adult ,03 medical and health sciences ,Hyperaemia ,0302 clinical medicine ,Internal medicine ,medicine.artery ,medicine ,Humans ,Popliteal Artery ,Exercise ,Leg ,business.industry ,Skeletal muscle ,General Medicine ,Popliteal artery ,medicine.anatomical_structure ,Regional Blood Flow ,Cardiology ,Endothelium, Vascular ,Stress, Mechanical ,medicine.symptom ,business ,Blood Flow Velocity ,030217 neurology & neurosurgery ,Muscle Contraction ,Artery - Abstract
NEW FINDINGS What is the central question of this study? We aimed to examine leg vascular responses to brief periods of inactivity. What is the main finding and its importance? We demonstrate that a mere 10 min of sitting is sufficient to impair leg microvascular function (reactive hyperaemia). However, conduit artery vasodilatation (flow-mediated dilatation) was unaffected, indicating maintained macrovascular function. Interestingly, immobile supine rest also resulted in a reduction in microvascular function alone that was prevented when calf muscle contractions were performed. Collectively, these data highlight the susceptibility of the microcirculation to short periods of inactivity and the beneficial role of skeletal muscle contraction for vascular health. ABSTRACT Prolonged sitting for 1-6 h has been shown to impair leg macrovascular [i.e. reduced flow-mediated dilatation (FMD)] and microvascular (i.e. reduced reactive hyperaemia) function. These impairments appear to be mediated through reductions in shear stress. Interestingly, a reduction in shear rate has been observed as early as 10 min into sitting. However, it is unknown whether this acute reduction in shear stress is sufficient to affect vascular function. Accordingly, we studied 18 young men and assessed popliteal artery FMD and reactive hyperaemia before (Baseline) and after (PostSit) a 10 min sitting period. Popliteal artery shear rate was significantly reduced during sitting (Baseline, 62 ± 35 s-1 ; 10 min sitting, 27 ± 13 s-1 ; P
- Published
- 2018
40. Fifty years of microneurography: learning the language of the peripheral sympathetic nervous system in humans
- Author
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Paul J. Fadel, Stephen A. Klassen, J. Kevin Shoemaker, and Mark B. Badrov
- Subjects
Sympathetic nervous system ,Sympathetic Nervous System ,Microneurography ,Physiology ,Neurophysiology ,Review ,Muscle sympathetic nerve activity ,030204 cardiovascular system & hematology ,History, 21st Century ,Recruitment strategies ,03 medical and health sciences ,0302 clinical medicine ,Reflex cardiovascular control ,Medicine and Health Sciences ,Humans ,Medicine ,Primary component ,Peripheral Nerves ,Muscle, Skeletal ,Neural control of the circulatoin ,business.industry ,Electrodiagnosis ,General Neuroscience ,History, 20th Century ,Kinesiology ,Electrophysiological Phenomena ,Peripheral ,body regions ,medicine.anatomical_structure ,Neurovascular Coupling ,business ,Microelectrodes ,Neuroscience ,030217 neurology & neurosurgery ,Homeostasis - Abstract
© 2018 American Physiological Society. All rights reserved. As a primary component of homeostasis, the sympathetic nervous system enables rapid adjustments to stress through its ability to communicate messages among organs and cause targeted and graded end organ responses. Key in this communication model is the pattern of neural signals emanating from the central to peripheral components of the sympathetic nervous system. But what is the communication strategy employed in peripheral sympathetic nerve activity (SNA)? Can we develop and interpret the system of coding in SNA that improves our understanding of the neural control of the circulation? In 1968, Hagbarth and Vallbo (Hagbarth KE, Vallbo AB. Acta Physiol Scand 74: 96–108, 1968) reported the first use of microneurographic methods to record sympathetic discharges in peripheral nerves of conscious humans, allowing quantification of SNA at rest and sympathetic responsiveness to physiological stressors in health and disease. This technique also has enabled a growing investigation into the coding patterns within, and cardiovascular outcomes associated with, postganglionic SNA. This review outlines how results obtained by microneurographic means have improved our understanding of SNA outflow patterns at the action potential level, focusing on SNA directed toward skeletal muscle in conscious humans.
- Published
- 2018
41. Exaggerated Vasoconstriction to Spontaneous Bursts of Muscle Sympathetic Nerve Activity in Healthy Young Black Men
- Author
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Seth W. Holwerda, Jennifer R. Vranish, Thales C. Barbosa, David M. Keller, Paul J. Fadel, Benjamin E. Young, Jordan C. Patik, and Daniel P. Credeur
- Subjects
Adult ,Male ,medicine.medical_specialty ,Mean arterial pressure ,Sympathetic nervous system ,Sympathetic Nervous System ,Rest ,Population ,Hemodynamics ,Blood Pressure ,030204 cardiovascular system & hematology ,Muscle, Smooth, Vascular ,White People ,03 medical and health sciences ,0302 clinical medicine ,Heart Rate ,Internal medicine ,Heart rate ,Internal Medicine ,medicine ,Humans ,education ,education.field_of_study ,business.industry ,United States ,Black or African American ,Femoral Artery ,medicine.anatomical_structure ,Blood pressure ,Vasoconstriction ,Cardiology ,Vascular resistance ,Vascular Resistance ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Blacks have the highest prevalence of hypertension, putting them at greater risk of cardiovascular disease and death. Previous studies have reported that, relative to whites, healthy black men have augmented pressor responses to sympathoexcitatory stressors. Although important, these studies do not inform about the resting state and the influence of spontaneous changes in resting muscle sympathetic nerve activity (MSNA). Likewise, little is known about the transduction of MSNA into a vascular response at rest on a beat-to-beat basis. Accordingly, we tested the hypothesis that relative to whites, blacks would exhibit greater vasoconstriction and pressor responses following spontaneous bursts of MSNA. Mean arterial pressure, common femoral artery blood flow, and MSNA were continuously recorded during 20 minutes of supine rest in 35 young healthy men (17 blacks and 18 whites). Signal averaging was used to characterize changes in leg vascular conductance, total vascular conductance, and mean arterial pressure following spontaneous MSNA bursts. Blacks demonstrated significantly greater decreases in leg vascular conductance (blacks: −15.0±1.0%; whites: −11.5±1.2%; P =0.042) and total vascular conductance (blacks: −8.6±0.9%; whites: −5.1±0.4%; P =0.001) following MSNA bursts, which resulted in greater mean arterial pressure increases (blacks: +5.2±0.6 mm Hg; whites: +3.9±0.3 mm Hg; P =0.04). These exaggerated responses in blacks compared with whites were present whether MSNA bursts occurred in isolation (singles) or in combination (multiples) and were graded with increases in burst height. Collectively, these findings suggest that healthy young black men exhibit augmented sympathetic vascular transduction at rest and provide novel insight into potential mechanism(s) by which this population may develop hypertension later in life.
- Published
- 2018
42. Integration of Central and Peripheral Regulation of the Circulation during Exercise: Acute and Chronic Adaptations
- Author
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Paul J. Fadel, Philip S. Clifford, Patrick J. Mueller, Craig G. Crandall, and Scott A. Smith
- Subjects
Central Nervous System ,medicine.medical_specialty ,Sympathetic Nervous System ,Central nervous system ,Disease ,030204 cardiovascular system & hematology ,Cardiovascular Physiological Phenomena ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,medicine ,Humans ,Exercise physiology ,Exercise ,Sedentary lifestyle ,Neurotransmitter Agents ,business.industry ,Hemodynamics ,Motor control ,Baroreflex ,Adaptation, Physiological ,Respiratory support ,Peripheral ,medicine.anatomical_structure ,business ,030217 neurology & neurosurgery - Abstract
Physical movement lasting any more than a few seconds (e.g., exercise), requires coordination of motor control with concomitant changes in the cardiovascular and respiratory support necessary to respond to the rapid increases in metabolic demand. Without such coordination, delivery of oxygen and removal of waste products become rate limiting and will restrict the duration, speed, and quality of movement. Fortunately, under healthy conditions, the central and peripheral nervous systems contribute importantly to this remarkable level of coordination via complex mechanisms that remain to be fully elucidated. The purposes of this review are to present the current state of knowledge regarding: (i) mechanisms by which the body maintains appropriate perfusion pressure to all organs during acute bouts of exercise, and (ii) alterations occurring in these mechanisms via central nervous system adaptations when exercise is performed or not performed on a regular basis (e.g., physically active versus sedentary lifestyle, respectively). Results from studies performed in humans and laboratory animals provide the reader a well-rounded knowledge base. They are intended to instill an appreciation of what is known, and not known, about how the brain regulates the cardiovascular system during acute bouts of exercise, and the adaptations that occur when individuals exercise regularly versus when chronically sedentary. Discussion of the latter is intended to provide novel mechanisms for the increased incidence of cardiovascular disease in sedentary individuals versus a reduced incidence in individuals who are regularly active. © 2018 American Physiological Society. Compr Physiol 8:103-151, 2018.
- Published
- 2017
43. Prolonged sitting leg vasculopathy: contributing factors and clinical implications
- Author
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Paul J. Fadel and Jaume Padilla
- Subjects
medicine.medical_specialty ,Endothelium ,Physiology ,Arterial disease ,Posture ,Review ,Disease ,030204 cardiovascular system & hematology ,Sitting ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Vascular Diseases ,Prolonged sitting ,Leg ,business.industry ,Healthy subjects ,030229 sport sciences ,Sedentary behavior ,Blood flow ,medicine.anatomical_structure ,Physical therapy ,Cardiology ,Endothelium, Vascular ,Sedentary Behavior ,Shear Strength ,Cardiology and Cardiovascular Medicine ,business - Abstract
Atherosclerotic peripheral artery disease primarily manifests in the medium- to large-sized conduit arteries of the lower extremities. However, the factors underlying this increased vulnerability of leg macrovasculature to disease are largely unidentified. On the basis of recent studies, we propose that excessive time spent in the sitting position and the ensuing reduction in leg blood flow-induced shear stress cause endothelial cell dysfunction, a key predisposing factor to peripheral artery disease. In particular, this review summarizes the findings from laboratory-based sitting studies revealing acute leg vascular dysfunction with prolonged sitting in young healthy subjects, discusses the primary physiological mechanisms and the potential long-term implications of such leg vasculopathy with repeated exposure to prolonged sitting, as well as identifies strategies that may be effective at evading it.
- Published
- 2017
44. Influence of sex on microvascular and macrovascular responses to prolonged sitting
- Author
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Jaume Padilla, Paul J. Fadel, Jordan C. Patik, Benjamin E. Young, Jasdeep Kaur, and Jennifer R. Vranish
- Subjects
Male ,medicine.medical_specialty ,Physiology ,media_common.quotation_subject ,Posture ,Flow mediated dilation ,Hyperemia ,030204 cardiovascular system & hematology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,medicine.artery ,medicine ,Humans ,Contrast (vision) ,Popliteal Artery ,Prolonged sitting ,Reactive hyperemia ,media_common ,Leg ,Sex Characteristics ,Ultrasonography, Doppler, Duplex ,business.industry ,Microcirculation ,Hemodynamics ,030229 sport sciences ,Sedentary behavior ,Healthy Volunteers ,Popliteal artery ,Surgery ,Vasodilation ,Regional Blood Flow ,Microvessels ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Increased daily sitting time is associated with greater cardiovascular risk, and, on average, women are more sedentary than men. Recent reports have demonstrated that prolonged sitting reduces lower leg microvascular (reactive hyperemia) and macrovascular [flow-mediated dilation (FMD)] vasodilator function. However, these studies have predominately included men, and the effects of sitting in young women are largely unexplored. This becomes important given known sex differences in vascular function. Thus, herein, we assessed popliteal artery reactive hyperemia and FMD before and after a 3-h sitting period in healthy young women ( n = 12) and men ( n = 8). In addition, resting popliteal artery hemodynamics (duplex Doppler ultrasound) and calf circumference were measured before, during, and after sitting. Resting popliteal artery shear rate was reduced to a similar extent in both groups during the sitting period (women: −48.5 ± 8.4 s−1 and men: −52.9 ± 12.3 s−1, P = 0.45). This was accompanied by comparable increases in calf circumference in men and women ( P = 0.37). After the sitting period, popliteal artery FMD was significantly reduced in men (PreSit: 5.5 ± 0.9% and PostSit: 1.6 ± 0.4%, P < 0.001) but not women (PreSit: 4.4 ± 0.6% and PostSit: 3.6 ± 0.6%, P = 0.29). In contrast, both groups demonstrated similar reductions in hyperemic blood flow area under the curve (women: −28,860 ± 5,742 arbitrary units and men: −28,691 ± 9,685 arbitrary units, P = 0.99), indicating impaired microvascular reactivity after sitting. These findings indicate that despite comparable reductions in shear rate during 3 h of uninterrupted sitting, macrovascular function appears protected in some young women but the response was variable, whereas men exhibited more consistent reductions in FMD. In contrast, the leg microvasculature is susceptible to similar sitting-induced impairments in men and women. NEW & NOTEWORTHY We demonstrate that leg macrovascular function was consistently reduced in young men but not young women after prolonged sitting. In contrast, both men and women exhibited similar reductions in leg microvascular reactivity after sitting. These data demonstrate, for the first time, sex differences in vascular responses to prolonged sitting.
- Published
- 2017
45. Increased monocyte-derived reactive oxygen species in type 2 diabetes: role of endoplasmic reticulum stress
- Author
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Robert M. Restaino, Shekhar H. Deo, Paul J. Fadel, Alan R. Parrish, and Jaume Padilla
- Subjects
0301 basic medicine ,chemistry.chemical_classification ,medicine.medical_specialty ,Reactive oxygen species ,NADPH oxidase ,endocrine system diseases ,Endoplasmic reticulum ,Monocyte ,General Medicine ,Biology ,medicine.disease_cause ,Peripheral blood mononuclear cell ,Endothelial stem cell ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Internal medicine ,Immunology ,medicine ,Unfolded protein response ,biology.protein ,Oxidative stress - Abstract
Recent evidence suggests that exposure of human monocytes to glucolipotoxic media to mimic the composition of plasma of patients with type 2 diabetes (T2D) results in the induction of endoplasmic reticulum stress markers and formation of reactive oxygen species (ROS). The extent to which these findings translate to patients with T2D remains unclear. Thus, we first measured ROS (dihydroethidium fluorescence) in peripheral blood mononuclear cells (PBMCs) from whole blood of T2D patients (n = 8) and compared to age matched healthy controls (n = 8). T2D patients exhibited greater basal intracellular ROS (mean±SD, +3.4 ± 1.4 fold; P
- Published
- 2017
46. Obesity, type 2 diabetes, and impaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1
- Author
-
Jaume Padilla, Camila Manrique, Daniel P. Credeur, Paul J. Fadel, Leryn J. Reynolds, and John P. Thyfault
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,endocrine system diseases ,Nitric Oxide Synthase Type III ,Physiology ,medicine.medical_treatment ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Biology ,Renal Circulation ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Thinness ,Physiology (medical) ,Internal medicine ,No synthase ,medicine ,Humans ,Insulin ,Obesity ,Muscle, Skeletal ,Endothelin-1 ,nutritional and metabolic diseases ,Skeletal muscle ,Blood flow ,Middle Aged ,medicine.disease ,Endothelin 1 ,Femoral Artery ,Glucose ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Diabetes Mellitus, Type 2 ,Glucose Clamp Technique ,Female ,Insulin Resistance ,Nitric Oxide Synthase ,Research Article - Abstract
Increased endothelin-1 (ET-1) and reduced endothelial nitric oxide phosphorylation (peNOS) are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), but studies examining these links in humans are limited. We sought to assess basal and insulin-stimulated endothelial signaling proteins (ET-1 and peNOS) in skeletal muscle from T2D patients. Ten obese T2D [glucose disposal rate (GDR): 6.6 ± 1.6 mg·kg lean body mass (LBM)−1·min−1] and 11 lean insulin-sensitive subjects (Lean GDR: 12.9 ± 1.2 mg·kg LBM−1·min−1) underwent a hyperinsulinemic-euglycemic clamp with vastus lateralis biopsies taken before and 60 min into the clamp. Basal biopsies were also taken in 11 medication-naïve, obese, non-T2D subjects. ET-1, peNOS (Ser1177), and eNOS protein and mRNA were measured from skeletal muscle samples containing native microvessels. Femoral artery blood flow was assessed by duplex Doppler ultrasound. Insulin-stimulated blood flow was reduced in obese T2D (Lean: +50.7 ± 6.5% baseline, T2D: +20.8 ± 5.2% baseline, P < 0.05). peNOS/eNOS content was higher in Lean under basal conditions and, although not increased by insulin, remained higher in Lean during the insulin clamp than in obese T2D ( P < 0.05). ET-1 mRNA and peptide were 2.25 ± 0.50- and 1.52 ± 0.11-fold higher in obese T2D compared with Lean at baseline, and ET-1 peptide remained 2.02 ± 1.9-fold elevated in obese T2D after insulin infusion ( P < 0.05) but did not increase with insulin in either group ( P > 0.05). Obese non-T2D subjects tended to also display elevated basal ET-1 ( P = 0.06). In summary, higher basal skeletal muscle expression of ET-1 and reduced peNOS/eNOS may contribute to a reduced insulin-stimulated leg blood flow response in obese T2D patients.NEW & NOTEWORTHY Although impairments in endothelial signaling are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), human studies examining these links are limited. We provide the first measures of nitric oxide synthase and endothelin-1 expression from skeletal muscle tissue containing native microvessels in individuals with and without T2D before and during insulin stimulation. Higher basal skeletal muscle expression of endothelin-1 and reduced endothelial nitric oxide phosphorylation (peNOS)/eNOS may contribute to reduced insulin-stimulated blood flow in obese T2D patients.
- Published
- 2017
47. Editorial to accompany exchange of views: Role of exercise pressor reflex in control of ventilation during exercise
- Author
-
Paul J. Fadel
- Subjects
Nutrition and Dietetics ,Physiology ,business.industry ,Control of respiration ,Physiology (medical) ,Anesthesia ,Reflex ,Breathing ,Medicine ,General Medicine ,business - Published
- 2020
48. Call for papers on racial differences in cardiovascular and cerebrovascular physiology
- Author
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Paul J. Fadel, Irving H. Zucker, Austin T. Robinson, and Nisha Charkoudian
- Subjects
Gerontology ,Cerebrovascular Physiology ,Social Determinants of Health ,Physiology ,business.industry ,Racial Groups ,MEDLINE ,Brain ,Health Status Disparities ,Cardiovascular System ,Risk Assessment ,Race Factors ,Cerebrovascular Disorders ,Race (biology) ,Cardiovascular Diseases ,Risk Factors ,Physiology (medical) ,Humans ,Medicine ,Racial differences ,Cardiology and Cardiovascular Medicine ,business ,Risk assessment ,Life Style - Published
- 2020
49. Letter to the editor: Sympathetically mediated increases in cardiac output, or peripheral vasoconstriction as primary regulator of BP during hyperinsulinemia?
- Author
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Paul J. Fadel, Seth W. Holwerda, Benjamin E. Young, and David M. Keller
- Subjects
medicine.medical_specialty ,Cardiac output ,Letter to the editor ,Physiology ,business.industry ,Peripheral vasoconstriction ,Regulator ,medicine.disease ,Physiology (medical) ,Internal medicine ,Cardiology ,medicine ,Hyperinsulinemia ,Cardiology and Cardiovascular Medicine ,business - Published
- 2020
50. Reply from Paul J. Fadel
- Author
-
Paul J. Fadel
- Subjects
Nutrition and Dietetics ,Physiology ,business.industry ,Physiology (medical) ,Medicine ,General Medicine ,business - Published
- 2020
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