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This study supports differences in microvascular endothelial function and nitric oxide (NO)-dependent vasodilation between women in low hormone phases of two hormonal exposures and men. However, when separated into subgroups of hormonal exposure, women during placebo pills of oral contraceptive pill (OCP) use have greater NO-dependent vasodilation than naturally cycling women in their menstrual phase and men. These data improve knowledge of sex differences and the effect of OCP use on microvascular endothelial function.

Endothelin-1 A receptors (ETARs) have been shown to reduce endothelial function independently and through increased production of superoxide. We show that independent ETAR inhibition increases microvascular endothelial function in non-Hispanic Black young adults. However, administration of a superoxide dismutase mimetic alone and in combination with ETAR inhibition had no effect on microvascular endothelial function suggesting that, in the cutaneous microvasculature, the negative effects of ETAR in non-Hispanic Black young adults are independent of superoxide production.

What is the main observation in this case? The main observation of this case report is substantial improvement in cutaneous microvascular endothelial function after cessation of long-term use of a fourth-generation oral contraceptive pill. This improvement appears independent of relative changes in the contribution of nitric oxide. What insights does it reveal? Our findings suggest that cessation of long-term, fourth-generation oral contraceptive pill use improves endothelial function within 20 months of cessation.The purpose of this case report was to evaluate in vivo endothelial function and nitric oxide (NO)-dependent vasodilatation before and after the cessation of long-term (11-12 years) fourth-generation oral contraceptive pill (OCP) use in one young, healthy and premenopausal woman. This retrospective analysis includes data from six experimental visits: three visits during months 133-144 of fourth-generation OCP use and three visits 19-22 months after OCP cessation. Endothelium-dependent and NO-dependent vasodilatation were assessed in the cutaneous microvasculature using laser-Doppler flowmetry, a rapid local heating protocol (39°C, 0.1°C/s) and pharmacological perfusion through intradermal microdialysis fibres. The participant had consistent medical history and lifestyle behaviours throughout both hormonal exposures. Data are presented as the mean (SD). Endothelium-dependent vasodilatation was 42 (10)% of site-specific maximal cutaneous vascular conductance (CVC

Metabolomics identifies molecular products produced in response to numerous stimuli, including both adaptive (includes exercise training) and disease processes. We analyzed a longitudinal cohort of American-style football (ASF) athletes, who reliably acquire maladaptive cardiovascular (CV) phenotypes during competitive training, with high-resolution metabolomics to determine whether metabolomics can discriminate exercise-induced CV adaptations from early CV pathology.Matched discovery ( n = 42) and validation ( n = 40) multicenter cohorts of collegiate freshman ASF athletes were studied with longitudinal echocardiography, applanation tonometry, and high-resolution metabolomics. Liquid chromatography-mass spectrometry identified metabolites that changed ( P0.05, false discovery rate0.2) over the season. Metabolites demonstrating similar changes in both cohorts were further analyzed in linear and mixed-effects models to identify those associated with left ventricular mass, tissue-Doppler myocardial E ' velocity (diastolic function), and arterial function (pulse wave velocity).In both cohorts, 20 common metabolites changed similarly across the season. Metabolites reflective of favorable CV health included an increase in arginine and decreases in hypoxanthine and saturated fatty acids (heptadecanoate, arachidic acid, stearate, and hydroxydecanoate). In contrast, metabolic perturbations of increased lysine and pipecolate, reflective of adverse CV health, were also observed. Adjusting for player position, race, height, and changes in systolic blood pressure, weight, and pulse wave velocity, increased lysine ( β = 0.018, P = 0.02) and pipecolate ( β = 0.018, P = 0.02) were associated with increased left ventricular mass index. In addition, increased lysine ( β = -0.049, P = 0.01) and pipecolate ( β = -0.052, P = 0.008) were also associated with lower E ' (reduced diastolic function).ASF athletes seem to develop metabolomic changes reflective of both favorable CV health and early CV maladaptive phenotypes. Whether metabolomics can discriminate early pathologic CV transformations among athletes is a warranted future research direction.

ObjectivesAmerican-style football (ASF) athletes are at risk for the development of concentric left ventricular hypertrophy (C-LVH), an established cardiovascular risk factor in the general population. We sought to address whether black race is associated with acquired C-LVH in collegiate ASF athletes.MethodsCollegiate ASF athletes from two National Collegiate Athletic Association Division-I programmes were recruited as freshmen between 2014 and 2019 and analysed over 3 years. Demographics (neighbourhood family income) and repeated clinical characteristics and echocardiography were recorded longitudinally at multiple timepoints. A mixed-modelling approach was performed to evaluate acquired C-LVH in black versus white athletes controlling for playing position (linemen (LM) and non-linemen (NLM)), family income, body weight and blood pressure.ResultsAt baseline, black athletes (N=124) were more often NLM (72% vs 54%, p=0.005) and had lower median neighbourhood family income ($54 119 vs $63 146, p=0.006) compared with white athletes (N=125). While both black and white LM demonstrated similar increases in C-LVH over time, among NLM acquired C-LVH was more common in black versus white athletes (postseason year-1: N=14/89 (16%) vs N=2/68 (3%); postseason year-2: N=9/50 (18%) vs N=2/32 (6%); postseason year-3: N=8/33 (24%) vs N=1/13 (8%), p=0.005 change over time). In stratified models, black race was associated with acquired C-LVH in NLM (OR: 3.70, 95% CI 1.12 to 12.21, p=0.03) and LM was associated with acquired C-LVH in white athletes (OR: 3.40, 95% CI 1.03 to 11.27, p=0.048).ConclusionsIndependent of family income and changes in weight and blood pressure, black race was associated with acquired C-LVH among collegiate ASF NLM and LM was associated with acquired C-LVH in white athletes.

We tested the hypothesis that inducible nitric oxide synthase (iNOS) contributes to reduced nitric oxide (NO)-dependent vasodilation in non-Hispanic Blacks and prehypertensive non-Hispanic Whites. Twenty Black and twenty White participants (10 normotensive, 10 prehypertensive per group; n = 40 total) participated in this study. Participants were instrumented with two microdialysis fibers, and each site was randomized as control (lactated Ringer) or iNOS inhibition (0.1 mM 1400W). Laser-Doppler flow probes and local heaters were used to measure skin blood flow and heat the skin to induce vasodilation, respectively. Each site was heated from 33°C to 39°C (rate: 0.1°C/s). Once a plateau was established, 20 mM nitro-l-arginine methyl ester (l-NAME), a nonspecific NOS inhibitor, was infused at each site to quantify NO-dependent vasodilation. At control sites, %NO-dependent vasodilation was reduced in prehypertensive Whites (47 ± 10%NO) and in both normotensive and prehypertensive Blacks (39 ± 9%NO and 28 ± 5%NO, respectively) relative to normotensive Whites (73 ± 8%NO; P < 0.0001 for all comparisons). Compared with respective control sites, iNOS inhibition increased NO-dependent vasodilation in prehypertensive Whites (68 ± 8%NO) and in both normotensive and prehypertensive Blacks (78 ± 8%NO and 55 ± 6%NO, respectively; P < 0.0001 for all comparisons). We failed to find an effect for normotensive Whites (77 ± 7%NO). After iNOS inhibition, %NO-dependent vasodilation was similar between normotensive Whites, prehypertensive Whites, and normotensive Blacks. Inhibition of iNOS increased NO-dependent vasodilation to a lesser extent in prehypertensive Blacks. These data suggest that iNOS contributes to reduced NO-dependent vasodilation in prehypertension and in Black participants. NEW & NOTEWORTHY Inducible nitric oxide synthase (iNOS) is typically upregulated in conditions of increased oxidative stress and may have detrimental effects on the vasculature. Endothelial nitric oxide (NO), which is cardioprotective, is reduced in prehypertensive non-Hispanic Whites and in non-Hispanic Blacks. We found that inhibition of iNOS can increase endothelial NO-dependent vasodilation in prehypertensive White participants and in both normotensive and prehypertensive Black participants.

PURPOSE OF REVIEW: Anomalous aortic origins of the coronary arteries (AAOCA) are a primary cause of sudden cardiac death in athletes. This review will detail the epidemiology, pathophysiology, and risk stratification of AAOCA, while also highlighting return-to-play considerations for athletes. RECENT FINDINGS: Sport pre-participation cardiovascular screening methods lack sensitivity and specificity in the identification of AAOCA. For the symptomatic athlete, clinicians must maintain a heightened clinical suspicion for AAOCA in order to proceed with appropriate cardiac imaging and functional assessments. Anomalous origin of the left coronary artery with an interarterial course is considered high-risk and requires sport restriction until surgical correction. In contrast, risks associated with anomalous origin of the right coronary artery are controversial, thus management and sports eligibility decisions may incorporate principles of shared-decision making. SUMMARY: Management options for athletes with AAOCA are complex, requiring a comprehensive clinical evaluation. While advances in multimodality cardiovascular imaging and physiologic functional assessments have improved AAOCA risk stratification, best practice treatment strategies for some AAOCA subtypes remain uncertain. As such, clinical management and sport eligibility decisions require an individualized approach. Future prospective data will guide optimization of treatment strategies for athletes with AAOCA.

Many studies of vascular function limit the testing of premenopausal female participants to periods when female sex hormones, either endogenous or exogenous, are at their lowest concentration. This practice, when not part of the specific research question, may limit data surrounding the predominant physiological state of premenopausal females and pose a threat to external validity. In this Perspective, we briefly review the literature on the effect of female sex hormones on vascular function and discuss when limiting experimental testing to a certain phase of the menstrual cycle (MC) or oral contraceptive (OC) use may be appropriate. The goal of this Perspective is to open a dialog that may enhance data validity and the overall understanding of vascular function in premenopausal females.

The purpose of this study was to investigate the effect of race and subclinical elevations in blood pressure (i.e., prehypertension) on cutaneous sensory nerve-mediated and nitric oxide (NO)-dependent vasodilation. We recruited participants who self-identified as either non-Hispanic black (n = 16) or non-Hispanic white (n = 16). Within each group, participants were subdivided as either normotensive (n = 8 per group) or prehypertensive (n = 8 per group). Each participant was instrumented with four intradermal microdialysis fibers: 1) control (lactated Ringer’s), 2) 5% lidocaine (sensory nerve inhibition), 3) 20 mM N(ω)-nitro-l-arginine methyl ester (l-NAME) (NO synthase inhibition), and 4) lidocaine + l-NAME. Skin blood flow was assessed via laser-Doppler flowmetry, and each site underwent local heating from 33°C to 39°C. At the plateau, 20 mM l-NAME were infused at control and lidocaine sites to quantify NO-dependent vasodilation. Maximal vasodilation was induced via 54 mM sodium nitroprusside and local heating to 43°C. Data are means ± SD. Sensory nerve-mediated cutaneous vasodilation was reduced in prehypertensive non-Hispanic white (34 ± 7%) and both non-Hispanic black groups (normotensive, 20 ± 9%, prehypertensive, 24 ± 15%) relative to normotensive non-Hispanic whites (54 ± 12%). NO-dependent vasodilation was also reduced in prehypertensive non-Hispanic white (41 ± 7%) and both non-Hispanic black groups (normotensive, 44 ± 7%, prehypertensive, 19 ± 7%) relative to normotensive non-Hispanic whites (60 ± 11%). The decrease in NO-dependent vasodilation in prehypertensive non-Hispanic blacks was further reduced relative to all other groups. These data suggest subclinical increases in blood pressure adversely affect sensory-mediated and NO-dependent vasodilation in both non-Hispanic blacks and whites. NEW & NOTEWORTHY Overt hypertension is known to reduce cutaneous sensory nerve-mediated and nitric oxide (NO)-dependent vasodilation, but the effect of subclinical increases in blood pressure (i.e., prehypertension) is unknown. The combined effect of race and prehypertension is also unknown. In this study, we found that prehypertension reduces cutaneous sensory nerve-mediated and NO-dependent vasodilation in both non-Hispanic white and black populations, with the greatest reductions observed in prehypertensive non-Hispanic blacks. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/race-blood-pressure-and-microvascular-function/.