47 results on '"Physiology"'
Search Results
2. Exploratory study of factors related to educational scores of first preclinical year medical students.
- Author
-
Chantacha Sitticharoon, Sorachai Srisuma, Sawita Kanavitoon, and Sarawut Summachiwakij
- Subjects
- *
GRADING of students -- Universities & colleges , *MEDICAL schools , *PHYSIOLOGY education (Higher) , *ANATOMY education in universities & colleges , *BIOCHEMISTRY education in universities & colleges , *MEDICAL science education - Abstract
The relationships among the scores of major subjects taught in the first preclinical year of a Thai medical school, previous academic achievements, and daily life activities are rarely explored. We therefore performed an exploratory study identifying various factors possibly related to the educational scores of these medical students. Questionnaires were sent out to all first preclinical year medical students, with 79.8% being returned (245/307 questionnaires). Positive correlations were revealed between the premedical year grade point average (pre-MD GPA) and anatomy, physiology, and biochemistry scores (R = 0.664, 0.521, and 0.653, respectively, P < 0.001 for all) by Pearson's method. Using multiple linear regression analysis, anatomy scores could be predicted by pre-MD GPA, student satisfaction with anatomy, the percentage of expected reading, monthly earnings, reading after class and near exam time, and duration of sleeping periods near exam time (R = 0.773, R2 = 0.598, P < 0.001). Physiology scores could be estimated by pre-MD GPA, the percentage of expected reading, monthly earnings, and percentage of those who fell asleep during class and near exam time (R = 0.722, R2 = 0.521, P < 0.001). Biochemistry scores could be calculated by pre-MD GPA, the percentage of expected reading, motivation to study medicine, student satisfaction with biochemistry, and exam performance expectations (R = 0.794, R2 = 0.630, P < 0.001). In conclusion, pre-MD GPA and the percentage of expected reading are factors involved in producing good academic results in the first preclinical year. Anatomy and biochemistry, but not physiology, scores are influenced by satisfaction. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
3. PLACEBO AND THE NEW PHYSIOLOGY OF THE DOCTOR-PATIENT RELATIONSHIP.
- Author
-
Benedetti, Fabrizio
- Subjects
- *
PLACEBOS , *PHYSICIAN-patient relations , *BIOCHEMISTRY , *ANATOMY , *PHYSIOLOGY , *PHARMACOLOGY , *MATERIA medica , *PSYCHOLOGICAL factors - Abstract
Modern medicine has progressed in parallel with the advancement of biochemistry, anatomy, and physiology. By using the tools of modern medicine, the physician today can treat and prevent a number of diseases through pharmacology, genetics, and physical interventions. Besides this materia medica, the patient's mind, cognitions, and emotions play a central part as well in any therapeutic outcome, as investigated by disciplines such as psychoneuroendocrinoimmunology. This review describes recent findings that give scientific evidence to the old tenet that patients must be both cured and cared for. In fact, we are today in a good position to investigate complex psychological factors, like placebo effects and the doctor-patient relationship, by using a physiological and neuroscientific approach. These intricate psychological factors can be approached through biochemistry, anatomy, and physiology, thus eliminating the old dichotomy between biology and psychology. This is both a biomedical and a philosophical enterprise that is changing the way we approach and interpret medicine and human biology. In the first case, curing the disease only is not sufficient, and care of the patient is of tantamount importance. In the second case, the philosophical debate about the mind-body interaction can find some important answers in the study of placebo effects. Therefore, maybe paradoxically, the placebo effect and the doctor-patient relationship can be approached by using the same biochemical, cellular and physiological tools of the materia medica, which represents an epochal transition from general concepts such as suggestibility and power of mind to a true physiology of the doctor-patient interaction. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
4. Detecting physiological systems with laser speckle perfusion imaging of the renal cortex.
- Author
-
Scully, Christopher G., Mitrou, Nicholas, Braam, Branko, Cupples, William A., and Chon, Ki H.
- Subjects
- *
KIDNEY cortex , *SPECKLE interference , *LASER beam scattering , *BIOCHEMISTRY , *PHYSIOLOGY - Abstract
Laser speckle perfusion imaging (LSPI) has become an increasingly popular technique for monitoring vascular perfusion over a tissue surface. However, few studies have utilized the full range of spatial and temporal information generated by LSPI to monitor spatial properties of physiologically relevant dynamics. In this study, we extend the use of LSPI to analyze renal perfusion dynamics over a spatial surface of ~5 x 7 mm of renal cortex. We identify frequencies related to five physiological systems that induce temporal changes in renal vascular perfusion (cardiac flow pulse, respiratory-induced oscillations, baroreflex components, the myogenic response, and tubuloglomerular feedback) across the imaged surface and compare the results with those obtained from renal blood flow measurements. We find that dynamics supplied from global sources (cardiac, respiration, and baroreflex) present with the same frequency at all locations across the imaged surface, but the local renal autoregulation dynamics can be heterogeneous in their distribution across the surface. Moreover, transfer function analysis with forced blood pressure as the input yields the same information with laser speckle imaging or renal blood flow as the output during control, intrarenal infusion of Nω-nitro-Larginine methyl ester to enhance renal autoregulation, and intrarenal infusion of the rho-kinase inhibitor Y-27632 to inhibit vasomotion. We conclude that LSPI measurements can be used to analyze local as well as global renal perfusion dynamics and to study the properties of physiological systems across the renal cortex. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
5. Vascular metabolic dissipation in Murray's law.
- Author
-
Yi Liu and Kassab, Ghassan S.
- Subjects
- *
METABOLISM , *PHYSIOLOGY , *CORONARY arteries , *BLOOD pressure , *BLOOD vessels , *BIOCHEMISTRY - Abstract
The metabolic dissipation in Murray's minimum energy hypothesis includes only the blood metabolism. The metabolic dissipation of the vascular tree, however, should also include the metabolism of passive and active components of the vessel wall. In this study, we extend the metabolic dissipation to include blood metabolism, as well as passive and active components of the vessel wall. The analysis is extended to the entire vascular arterial tree rather than a single vessel as in Murray's formulation. The calculations are based on experimentally measured morphological data of coronary artery network and the longitudinal distribution of blood pressure along the tree. Whereas the model includes multiple dissipation sources, the total metabolic consumption of a complex vascular tree is found to remain approximately proportional to the cumulative arterial volume of the unit. This implies that the previously described scaling relations for the various morphological features (volume, length, diameter, and flow) remain unchanged under the generalized condition of metabolic requirements of blood and blood vessel wall. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
6. Pizza and pasta help students learn metabolism.
- Author
-
Passos, Renato M., Sé, Alexandre B., Wolff, Vanessa L., Nobrega, Yanna K. M., and Hermes-Lima, Marcelo
- Subjects
- *
METABOLISM , *BIOCHEMISTRY , *MEDICAL students , *COLLEGE students , *NUTRITION , *PIZZA , *PASTA products , *PROBLEM-based learning , *UREA - Abstract
In this article, we report on an experiment designed to improve the learning of metabolic biochemistry by nutrition and medical undergraduate students. Twelve students participated in a monitored lunch and had their blood extracted for analysis 1) before lunch, 2) 30 min after lunch, and 3) 3 h after lunch. The subjects were divided in two groups. One group had a hyperglicidic meal [pasta plus orange juice: 80% carbohydrate, 10% protein, and 10% lipid (estimated values)] and the other group had a hyperlipidic meal (calabresi pizza plus diet soda: 36% carbohydrate, 18% protein, and 46% lipid). Individual quantities of food were based on body mass index, age, and sex. The blood parameters analyzed were glucose, triglycerides (TG), and urea. Glucose remained constant in the three measurements in both groups. The TG concentration in the pasta group was constant before and after lunch but increased significantly during the evening. In the pizza group, TG increased after lunch and remained constant in the evening. Levels of urea increased only in the evening, specially in the pizza group. These results were used for the final biochemistry exam. With the maximum score set as 10, the average score was 6.0 ± 2.4 (n = 102). We considered this activity a unique way of evaluating important issues on metabolism, because students had several hours to work on the final exam (with free access to a bibliography), It was also a good didactic experience (problem-based learning like) for the subject students, because they had to work in all phases of the experiment (idealization, realization, and analysis) and participated actively in the elaboration and correction of the exam. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
7. Human Multidrug Resistance ABCB and ABCG Transporters: Participation in a Chemoimmunity Defense System.
- Author
-
Sarkadi, Balázs, Homolya, László, Szakács, Gergely, and Váradi, András
- Subjects
- *
MULTIDRUG resistance , *ADENOSINE triphosphate , *PHYSIOLOGY , *BIOCHEMISTRY , *CYTOLOGY , *PROTEINS - Abstract
The article focuses on the general network characteristics of the multidrug resistance-ATP binding cassette (MDR-ABC) transporters, which function at the cellular and physiological tissue barriers. It gives an overview of the physiologic functions of these transporters and describes their general and mechanistic features. It discusses the biochemistry, cell biology, and physiology of the ABCB and ABCG proteins and their participation in a chemoimmunity defense system.
- Published
- 2006
- Full Text
- View/download PDF
8. Pizza and pasta help students learn metabolism.
- Author
-
Passos, Renato M., Sé, Alexandre B., Wolff, Vanessa L., Nobrega, Yanna K. M., and Hermes-Lima, Marcelo
- Abstract
In this article, we report on an experiment designed to improve the learning of metabolic biochemistry by nutrition and medical undergraduate students. Twelve students participated in a monitored lunch and had their blood extracted for analysis 1) before lunch, 2) 30 min after lunch, and 3) 3 h after lunch. The subjects were divided in two groups. One group had a hyperglicidic meal [pasta plus orange juice: 80% carbohydrate, 10% protein, and 10% lipid (estimated values)] and the other group had a hyperlipidic meal (calabresi pizza plus diet soda: 36% carbohydrate, 18% protein, and 46% lipid). Individual quantities of food were based on body mass index, age, and sex. The blood parameters analyzed were glucose, triglycerides (TG), and urea. Glucose remained constant in the three measurements in both groups. The TG concentration in the pasta group was constant before and after lunch but increased significantly during the evening. In the pizza group, TG increased after lunch and remained constant in the evening. Levels of urea increased only in the evening, specially in the pizza group. These results were used for the final biochemistry exam. With the maximum score set as 10, the average score was 6.0 ± 2.4 (n = 102). We considered this activity a unique way of evaluating important issues on metabolism, because students had several hours to work on the final exam (with free access to a bibliography). It was also a good didactic experience (problem-based learning like) for the subject students, because they had to work in all phases of the experiment (idealization, realization, and analysis) and participated actively in the elaboration and correction of the exam. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
9. "FUTILE CYCLING" IN PHYSIOLOGIC CONTROL SYSTEMS: A PRICE PAID FOR FINE CONTROL.
- Author
-
Aishwarya, Krishnamurthy, Rachana, Krishna, and Prakash, E. Sankaranarayanan
- Subjects
- *
PHYSIOLOGY , *HEART rate monitoring , *HEART beat , *METABOLISM , *NERVOUS system , *AUTONOMIC nervous system , *CENTRAL nervous system , *NEUROSCIENCES , *BIOCHEMISTRY - Abstract
The article studies futile cycling in physiologic control system. Substrate cycling refers to the simultaneous occurrence of opposing reactions at different rates. It is described as allowing fine tuning of metabolism. In the study, researchers drew an analogy between substrate cycling in metabolic pathways and tonic activity in opposing neural systems and applied it to the case of heart rate (HR) regulation by the two limbs of the autonomic nervous system. They concluded that the physiologic advantage of which cycling occurs is that fine HR modulation around the baseline value could be achieved faster, simultaneously and reciprocal changes in activity in two systems. The other assumptions made are that sympathetic and vagal systems for HR modulation are equipotent.
- Published
- 2005
- Full Text
- View/download PDF
10. D-Glucose upregulates adenosine transport in cultured human aortic smooth muscle cells.
- Author
-
Leung, George P. H., Man, Ricky Y. K., and Chung-Ming Tse
- Subjects
- *
ATHEROSCLEROSIS , *ETIOLOGY of diseases , *ADENOSINES , *CARDIAC research , *BIOCHEMISTRY , *PHYSIOLOGY - Abstract
The etiology of the atherosclerosis that occurs in diabetes mellitus is unclear. Adenosine has been shown to inhibit growth of rat aortic smooth muscle cells. Nucleoside transporters play an integral role in adenosine function by regulating adenosine levels in the vicinity of adenosine receptors. Therefore, we studied the effect of 25 mM D-glucose, which mimics hyperglycemia of diabetes, on adenosine transport in cultured human aortic smooth muscle cells (HASMCs). Although RT-PCR demonstrated the presence of equilibrative nucleoside transporter-1 (ENT-1) and ENT-2 mRNA, functional studies revealed that adenosine transport in HASMCs was predominantly mediated by ENT-1 and inhibited by nitrobenzylmercaptopurine riboside (NBMPR, IC50 = 0.69 ± 0.05 nM). Adenosine transport in HASMCs was increased by >30% after treatment for 48 h with 25 mM D-glucose, but not with equimolar D-mannitol and L-glucose. Kinetic studies showed that D-glucose increased Vmax of adenosine transport without affecting Kin. Similarly, D-glucose increased Bmax of high-affinity [³H]NBMPR binding, while the dissociation constant (Kδ) was not changed. Consistent with these observations, 25 mM D-glucose increased mRNA and protein expression of ENT-1. Treatment of serum-starved cells with the selective inhibitors of MAPK/ERK, PD-98059 (40 μM) and U-0126 (10 μM), abolished the effect of D-glucose on ENT-1. We conclude that D-glucose upregulates the protein and message expression and functional activity of ENT-1 in HASMCs, possibly via MAPK/ERK-dependent pathways. Pathologically, the increase in ENT-1 activity in diabetes may affect the availability of adenosine in the vicinity of adenosine receptors and, thus, alter vascular functions in diabetes. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
11. Comparison of Hsc70 orthologs from polar and temperate notothenioid fishes: differences in prevention of aggregation and refolding of denatured proteins.
- Author
-
Place, Sean P. and Hofmann, Gretchen E.
- Subjects
- *
MOLECULAR chaperones , *PROTEINS , *MOLECULAR biology , *BIOCHEMISTRY , *PHYSIOLOGY - Abstract
Although a great deal is known about the cellular function of molecular chaperones in general, very little is known about the effect of temperature selection on the function of molecular chaperones in nonmodel organisms. One major unanswered question is whether orthologous variants of a molecular chaperone from differential thermally adapted species vary in their thermal responses. To address this issue, we utilized a comparative approach to examine the temperature interactions of a major cytosolic molecular chaperone, Hsc70, from differently thermally adapted notothenioids. Using in vitro assays, we measured the ability of Hsc70 to prevent thermal aggregation of lactate dehydrogenase (LDH). We further compared the capacity of Hsc70 to refold chemically denatured LDH over the temperature range of -2 to +45°C. Hsc70 purified from the temperate species exhibited greater ability to prevent the thermal denaturation of LDH at 55°C compared with Hsc70 from the cold-adapted species. Furthermore, Hsc70 from the Antarctic species lost the ability to competently refold chemically denatured LDH at a lower temperature compared with Hsc70 from the temperate species. These data indicate the function of Hsc70 in notothenioid fishes maps onto their thermal history and that temperature selection has acted on these molecular chaperones. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
12. Adenosine A2A-receptor blockade abolishes the roll-off respiratory response to hypoxia in awake lambs.
- Author
-
Koos, Brian J., Kawasaki, Yoshikazu, Young-Han Kim, and Bohorquez, Fanor
- Subjects
- *
ADENOSINES , *HYPOXEMIA , *LAMBS , *RESPIRATORY organs , *BIOCHEMISTRY , *PHYSIOLOGY - Abstract
Adenosine (ADO) receptor antagonists (aminophylline, caffeine) blunt the respiratory roll-off response to hypoxia in the newborn. This study was designed to determine the ADO receptor subtype involved in the respiratory depression. Chronically catheterized lambs of 7–16 days of age breathed via face mask a gas mixture with a fraction of inspired 02 of 0.21 (normoxia) or 0.07 (hypoxia), while being infused intravascularly with 9-cyclopentyl- 1 ,3-dipropylxanthine (DPCPX; ADO A1-receptor antagonist, n = 8), ZM-241385 (ADO A2A-receptor antagonist, n = 7), or vehicle. Ventilation was measured at 20°C by a turbine transducer flowmeter. In normoxia [arterial Po2 (Pao2) of ∼83 Torr], infusion of vehicle did not alter cardiorespiratory measurements, whereas hypoxia (Pao2 of ∼31 Torr, 15 min) elicited biphasic effects on mean arterial pressure (transient increase), heart rate (HR; diminishing tachycardia), and minute ventilation. In the latter, hypoxia increased ventilation to a peak value of --2.5 times control within the first 3 mm, which was followed by a significant (P < 0.05) decline to -50% of the maximum increment over the subsequent 7 min. ZM-241385 abolished the hypoxic ventilatory roll-off and blunted the rate of rise in HR without affecting mean arterial pressure or rectal temperature responses. In normoxia, DPCPX increased ventilation and mean arterial pressure but did not change HR. Compared with vehicle, DPCPX did not significantly affect cardiorespiratory responses to hypoxemia (Pao2 of ∼31 Torr, 10 min). It is concluded that 1) ADO A2A receptors are critically involved in the ventilatory roll-off and HR responses to hypoxia, and 2) ADO A1 receptors, which are tonically active in cardiorespiratory control in normoxia, appear to have little impact on hypoxic ventilatory depression. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
13. Long-term hypoxia enhances proopiomelanocortin processing in the near-term ovine fetus.
- Author
-
Myers, Dean A., Bell, Paige A., Hyatt, Kimberly, Mlynarczyk, Malgorzata, and Ducsay, Charles A.
- Subjects
- *
FETUS , *PITUITARY hormones , *GLUCOCORTICOIDS , *HYPOXEMIA , *PROOPIOMELANOCORTIN , *BIOCHEMISTRY , *PHYSIOLOGY - Abstract
Secondary stressors in long-term hypoxic (LTH) fetal sheep lead to altered function of the hypothalamic-pituitary-adrenal axis. Although ACTH is considered the primary mediator of glucocorticoid production in fetal sheep, proopiomelanocortin (POMC) and 22-kDa pro-ACTH (22-kDa ACTH) have been implicated in the regulation of cortisol production in the ovine fetus. This study was designed to determine whether POMC expression and processing are altered after LTH. Pregnant ewes were maintained at high altitude (3,820 m) from day 30 of gestation to near term, when the animals were transported to the laboratory. Reduced Po2 was maintained by nitrogen infusion through a maternal tracheal catheter. On days 139–141, fetal anterior pituitaries were collected from normoxic control and LTH fetuses. We measured POMC and corticotrophin-releasing factor type 1 receptor (CRF1-R) mRNA using quantitative real-time PCR, and we used Western blot analysis for quantitation of ACTH, ACTH precursor, and CRF1-R proteins. We measured plasma ACTH1–39 using a two-site immunoradiometric assay specific for ACTH1–39. Plasma ACTH precursors were measured by ELISA. Anterior pituitary P0MG mRNA levels were not different between groups, whereas CRF1-R levels were significantly higher in the LTH anterior pituitaries com- pared with control (P < 0.05). In contrast, protein levels of POMC, CRF1-R, 22-kDa ACTH, and ACTH1–39 were significantly lower in the LTH group. Plasma concentrations of both ACTH precursors and ACTH1–39 were significantly elevated in LTH fetuses, whereas the ratio of plasma precursors to ACTH was significantly lower. We conclude that LTH results in enhanced POMG processing and/or release to ACTH and increased hypothalamic drive. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
14. Response to selection for photopenod responsiveness on the density and location of mature GnRH-releasing neurons.
- Author
-
Avigdor, Mauricio, Sullivan, Shannon D., and Heideman, Paul D.
- Subjects
- *
GONADOTROPIN releasing hormone , *PITUITARY hormone releasing factors , *NEURONS , *BIOCHEMISTRY , *PHYSIOLOGY - Abstract
Natural variation in neuroendocrine traits is poorly understood, despite the importance of variation in brain function and evolution. Most rodents in the temperate zones inhibit reproduction and other nonessential functions in short winter photoperiods, but some have little or no reproductive response. We tested whether genetic variability in reproductive seasonality is related to individual differences in the neuronal function of the gonadotropin-releasing hormone network, as assessed by the number and location of mature gonadotropin-releasing hormone-secreting neurons under inhibitory and excitatory photoperiods. The experiments used lines of Peromyscus leucopus previously developed by selection from a wild population. One line contained individuals reproductively inhibited by short photoperiod, and the other line contained individuals nonresponsive to short photoperiod. Expression of mature gonadotropin-releasing hormone (GnRH) immunoreactivity in the brain was detected using SMI-41 antibody in the single-labeled avidin-biotin-peroxidase-complex method. Nonresponsive mice had 50% more immunoreactive GnRH neurons than reproductively inhibited mice in both short- and long-day photoperiods. The greatest differences were in the anterior hypothalamus and preoptic areas. In contrast, we detected no significant within-lines differences in the number or location of immunoreactive GnRH neurons between photoperiod treatments. Our data indicate that high levels of genetic variation in a single wild population for a specific neuronal trait are related to phenotypic variation in a life history trait, i.e., winter reproduction. Variation in GnRH neuronal activity may underlie some of the natural reproductive and life history variation observed in wild populations of P. leucopus. Similar genetic variation in neuronal traits may be present in humans and other species. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
15. Adiponectin inhibits LPS-induced NF-κB activation and IL-6 production and increases PPARγ2 expression in adipocytes.
- Author
-
Ajuwon, Kolapo M. and Spurlock, Michael E.
- Subjects
- *
FAT cells , *HORMONES , *BIOMOLECULES , *TRANSCRIPTION factors , *BIOCHEMISTRY , *PHYSIOLOGY - Abstract
Obesity and insulin resistance are often associated with lower circulating adiponectin concentrations and elevated serum interleukin-6 (IL-6) and/or tumor necrosis factor-a (TNF-α). Adiponectin suppresses activation of nuclear factor-κB (NF-κB) in aortic endothelial cells and porcine macrophages. Accordingly, we hypothesized that adiponectin is an anti-inflammatory hormone and suppresses activation of NF-κB in adipocytes. Because peroxisome proliferator-activated receptor γ2 (PPARγ2) antagonizes the transcriptional activity of NF-κB, we determined whether adiponectin alters PPARγ2 expression in pig adipocytes. In addition, we determined whether interferon-γ alters the expression of PPARγ2 in the presence or absence of adiponectin. Primary adipocytes from pig subcutaneous adipose tissue were treated with or without lipopolysaccharide (LPS; 10 μg/ml) and adiponectin (30 μg/ml), and nuclear extracts were obtained for gel shift assays to assess nuclear localization of NF-κB. Whereas LPS induced an increase in NF-κB activation, adiponectin suppressed both NF-κB activation and the induction of IL-6 expression by LPS (P < 0.05). Similar results were obtained in 3T3-L1 adipocytes. In addition, adiponectin antagonized LPS-induced increase in TNF-α mRNA expression (P < 0.05) and tended (P < 0.065) to diminish its accumulation in the culture media in 3T3-L1 adipocytes. Adiponectin also induced an upregulation of PPARγ2 mRNA (P < 0.05). Although IFN-γ did not reduce the basal expression of PPARγ2, it suppressed PPARγ2 induction by adiponectin (P < 0.05). These findings indicate that adiponectin may be a local regulator of inflammation in the adipocyte and adipose tissue via its regulation of the NF-κB and PPARγ2 transcription factors. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
16. Ghrelin: Structure and Function.
- Author
-
Kojima, Masayasu and Kangawa, Kenji
- Subjects
- *
GHRELIN , *HORMONES , *SECRETION , *PHYSIOLOGY , *BIOCHEMISTRY - Abstract
Describes the structure and function of ghrelin. Details on the clinical application of ghrelin; Physiological functions of ghrelin; Regulation of ghrelin secretion and associated disease.
- Published
- 2005
- Full Text
- View/download PDF
17. Contribution of K+ATP channels to coronary vasomotor tone regulation is enhanced in exercising swine with a recent myocardial infarction.
- Author
-
Merkus, Daphne, Houweling, Birgit, van Vliet, Marion, and Duncker, Dirk J.
- Subjects
- *
HYPERTROPHY , *POTASSIUM , *VASOMOTOR system , *MYOCARDIAL infarction , *BIOCHEMISTRY , *PHYSIOLOGY , *BIOLOGY - Abstract
Previous studies demonstrated a decreased flow reserve in the hypertrophied myocardium early after myocardial infarction (MI). Previously, we reported that exacerbation of hemodynamic abnormalities and neurohumoral activation during exercise caused slight impairment of myocardial O2 supply in swine with a recent MI. We hypothesized that increased metabolic coronary vasodilation [via ATP-sensitive K+ (KATP+) channels and adenosine] may have partially compensated for the increased extravascular compressive forces and increased vasoconstrictor neurohormones, thereby preventing a more severe impairment of myocardial O2 balance. Chronically instrumented swine were exercised on a treadmill up to 85% of maximum heart rate. Under resting conditions, adenosine receptor blockade [8-phenyltheophylline (8-PT), 5 mg/kg iv] and KATP+ channel blockade (glibenclamide, 3 mg/kg iv) produced similar decreases in myocardial O2 supply in normal and Ml swine. However, while glibenclamide's effect waned in normal swine during exercise (P < 0.05), it was maintained in MI swine. 8-PT's effect was maintained during exercise and was not different between normal and MI swine. Finally, in normal swine combined treatment with 8-PT and glibenclamide produced a vasoconstrictor response that equaled the sum of the responses to blockade of the individual pathways. In contrast, in MI swine the vasoconstrictor response to 8-PT and glibenclamide was similar to that produced by glibenclamide alone. In conclusion, despite significant hemodynamic abnormalities in swine with a recent MI, myocardial O2 supply and O2 consumption in remodeled myocardium are still closely matched during exercise. This close matching is supported by increased KATP+ channel-mediated coronary vasodilation. Although the net vasodilator influence of adenosine was unchanged in remodeled myocardium, it became exclusively dependent on KATP+ channel opening. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
18. Acute adenosine preconditioning is mediated by p38 MAPK activation in discrete subcellular compartments.
- Author
-
Ballard-Croft, Cherry, Kristo, Gentian, Yoshimura, Yukihiro, Reid, Easton, Keith, Byron J., Mentzer Jr., Robert M., and Lasley, Robert D.
- Subjects
- *
ADENOSINES , *CARDIOLOGY , *ISCHEMIA , *BLOOD circulation disorders , *BIOCHEMISTRY , *PHYSIOLOGY , *BIOLOGY - Abstract
Although acute adenosine preconditioning (PC) is well established, the signaling pathways mediating this cardioprotection remain unclear. Because adenosine receptor agonists activate p38 MAPK and this kinase has been implicated in ischemic and pharmacological PC, the purpose of this study was to determine the role of p38 MAPK in acute adenosine receptor PC. The role of p38 MAPK activation in discrete subcellular compartments during ischemia-reperfusion was also determined. The following groups were used in an in vivo rat ischemia-reperfusion model: 1) control (10% DMSO iv), 2) the A1/A2a adenosine receptor AMP-579 (50 μg/kg iv), 3) AMP-579 + the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 μg/kg iv), 4) AMP-579 + the p38 MAPK inhibitor SB-203580 (1 mg/kg iv), and 5) SB-203580 alone. p38 MAPK activation was measured by Western blot analysis in cytosolic, mitochondrial, membrane, and nuclear/myofilament fractions obtained from hearts at preischemic, ischemic, and reperfusion time points. A significant reduction in infarct size was observed with AMP-579 PC, an effect blocked by DPCPX or SB-203580 pretreatment. AMP-579 treatment was associated with a significant increase in p38 MAPK activation in the nuclear/myofilament fraction before ischemia, whereas no activation of this kinase occurred during ischemia or reperfusion. In contrast, p38 MAPK was activated in the mitochondrial fraction by ischemia and in the cytosolic, mitochondrial, and membrane fractions by reperfusion in the control group. SB-203580 blocked the AMP-579-induced increase in phosphorylation of the downstream p38 substrate activating transcription factor-2. These results suggest a role for p38 MAPK activation in discrete subcellular compartments in acute adenosine A1 receptor PC. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
19. Effect of simvastatin on left ventricular mass in hypercholesterolemic rabbits.
- Author
-
Tsung-Ming Lee, Mei-Shu Lin, Tsai-Fwu Chou, and Nen-Chung Chang
- Subjects
- *
HYPERCHOLESTEREMIA , *HYPERLIPIDEMIA , *LEFT heart ventricle , *LABORATORY rabbits , *BIOCHEMISTRY , *PHYSIOLOGY , *BIOLOGY - Abstract
Epidemiological studies showed that hypercholesterolemia is associated with higher left ventricular mass. Endothelin signaling is activated in hyperlipidemic animals and may contribute to progressive ventricular hypertrophy. Simvastatin has been shown to inhibit endothelin-1. However, the behavior of simvastatin on ventricular hypertrophy in hyperlipidemic animals is not well understood. In this study, we evaluated the hemodynamic, biochemical, and morphological responses to simvastatin in cholesterol-led (1%) rabbits. The left ventricular weight increased 8 wk after cholesterol feeding compared with that in normocholesterolemic rabbits. Simvastatin at a clinical therapeutic dose (1.2 mg·kg-1·day-1) significantly decreased left ventricular weight by 14% and left ventricular myocyte sizes by 14% as isolated by enzymatic dissociation. Hypercholesterolemia upregulated ventricular preproendothelin-1 mRNA as assessed by real-time quantitative RT-PCR and elevated production of cardiac endothelin-1 concentration. The increased endothelin-1 responses can be inhibited after simvastatin administration. Left ventricular mass indexed by body weight positively correlated with tissue endothelin-1 levels (P = 0.0003). In Langendorff-perfused rabbit hearts, hyperlipidemia led to significant QT prolongation compared with normocholesterolemia, which can be reversed by administering simvastatin. In contrast, simvastatin-induced beneficial effects were reversed by the addition of mevalonate. The addition of bosentan, a nonspecific endothelin receptor blocker, improved the response in hypercholesterolemic rabbits and did not have additional beneficial effects in simvastatin-treated rabbits. The results of the present study suggest that the antihypertropic and electrocardiographic effects of simvastatin at a clinical therapeutic dose are mediated through inhibition of tissue endothelin-1 expression, which is linked to mevalonate metabolism, and result in an amelioration of cardiomyocyte hypertrophy development by an atherogenic diet. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
20. Regulatory response to washout of amniotic fluid in sheep.
- Author
-
Qin Yang, Davis, L., Hohimer, A., Faber, J., and Anderson, D.
- Subjects
- *
AMNIOTIC liquid , *SHEEP as laboratory animals , *EWES , *BIOCHEMISTRY , *PHYSIOLOGY , *BIOLOGY - Abstract
To test the hypothesis that a substance present in the amniotic fluid could serve as a regulator of amniotic fluid volume, we drained and discarded amniotic fluid while replacing it with lactated Ringer solution that was isotonic to amniotic fluid. Seven ewes with singleton fetuses at 119 ± 1 days of gestation (mean ± SE) were instrumented with multiple indwelling catheters in the pedal artery, pedal vein, and amniotic cavity. During the exchange periods, an average of 3,019 ± 171 ml/day of lactated Ringer solution was infused into the amniotic cavity while an equal amount of amniotic fluid was pumped out and discarded. During the control period, amniotic fluid composition and volume were not altered. Exchange and control periods started with the same amniotic fluid volume, lasted 3 or 4 days, and were randomized with regard to order. Amniotic fluid volume measured by vacuum drainage was 556 ± 98 ml at the end of the control period and 986 ± 209 ml (P = 0.03) at the end of the exchange period. Fetal arterial blood gases, hemodynamic parameters and the osmolality gradient between fetal plasma and amniotic fluid were not altered by the exchange process. A linear relationship between the control amniotic fluid volume and the volume at the end of the exchange period (P = 0.003) suggests that the animals with larger control volumes responded to isovolumic dilution with a larger volume increase. We conclude that amniotic fluid may contain a substance that regulates amniotic volume. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
21. FMLP-stimulated neutrophils increase endothelIal [Ca2+]i and microvessel permeability in the absence of adhesion: role of reactive oxygen species.
- Author
-
Zhu, Longkun, Castranova, Vince, and He, Pingnian
- Subjects
- *
NEUTROPHILS , *REACTIVE oxygen species , *ACTIVE oxygen in the body , *BIOCHEMISTRY , *PHYSIOLOGY , *BIOLOGY - Abstract
Our previous study demonstrated that firm attachment of leukocytes to microvessel walls does not necessarily increase microvessel permeability (Am J Physiol Heart Circ Physiol 283: H2420–H2430, 2002). To further understand the mechanisms of the permeability increase associated with leukocyte accumulation during acute inflammation, we investigated the direct relation of reactive oxygen species (ROS) release during neutrophil respiratory burst to changes in microvessel permeability and endothelial intracellular Ca2+ concentration ([Ca2+]i) in intact microvessels. ROS release from activated neutrophils was quantified by measuring changes in chemiluminescence. When isolated rat neutrophils (2 × 106/ml) were exposed to formyl-Met-Leu-Phe-OH (fMLP, 10 μM), chemiluminescence transiently increased from 1.2 ± 0.2 × 104 to a peak value of 6.7 ± 1.0 × 104 cpm/min (n = 12). Correlatively, perfusing individual microvessels with fMLP-stimulated neutrophils in suspension (2 × 107/ml) increased hydraulic conductivity (Lp) to 3.7 ± 0.4 times the control value (n = 5) and increased endothetial [Ca2+]i from 84 ± 7 nM to a mean peak value of 170 ± 7 nM. In contrast, perfusing vessels with fMLP alone did not affect basal Lp. Application of antioxidant agents, superoxide dismutase, vitamin C, or an iron chelator, deferoxamine mesylate, attenuated ROS release in fMLP-stimulated neutrophils and abolished increases in Lp. These results indicate that release of ROS from fMLP-stimulated neutrophils increases microvessel permeability and endothelial [Ca2+]i independently from leukocyte adhesion and the migration process. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
22. Direct measurement of transmural laminar architecture in the anterolateral wall of the ovine left ventricle: new implications for wall thickening mechanics.
- Author
-
Harrington, Katherine B., Rodriguez, Filiberto, Cheng, Allen, Langer, Frank, Ashikaga, Hiroshi, Daughters, George T., Criscione, John C., Ingels, Neil B., and Miller, D. Craig
- Subjects
- *
LEFT heart ventricle , *HEMODYNAMICS , *CARDIOLOGY , *BIOCHEMISTRY , *PHYSIOLOGY , *BIOLOGY - Abstract
Laminar, or sheet, architecture of the left ventricle (LV) is a structural basis for normal systolic and diastolic LV dynamics, but transmural sheet orientations remain incompletely characterized. We directly measured the transmural distribution of sheet angles in the ovine anterolateral LV wall. Ten Dorsett-hybrid sheep hearts were perfusion fixed in situ with 5% buffered glutaraldehyde at end diastole and stored in 10% formalin. Transmural blocks of myocardial tissue were excised, with the edges cut parallel to local circumferential, longitudinal, and radial-axes, and sliced into 1-mm-thick sections parallel to the epicardial tangent plane from epicardium to endocardium. Mean fiber directions were determined in each section from five measurements of fiber angles. Each section was then cut transverse to the fiber direction, and five sheet angles (β) were measured and averaged. Mean fiber angles progressed nearly linearly from -41° (SD 11) at the epicardium to +42° (SD 16) at the endocardium. Two families of sheets were identified at approximately +45° (β+) and -45° (β-). In the lateral region (n = 5), near the epicardium, sheets belonged to the β+ family: in the midwall, to the β- family; and near the endocardium, to the β+ family. This pattern was reversed in the basal anterior region (n = 4). Sheets were uniformly β- over the anterior papillary muscle (n = 2). These direct measurements of sheet angles reveal, for the first time, alternating transmural families of predominant sheet angles. This may have important implications in understanding wall mechanics in the normal and the failing heart. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
23. PPAR-γ activation fails to provide myocardial protection in ischemia and reperfusion in pigs.
- Author
-
Ya Xu, Gen, Michael, Li Lu, Fox, Jennifer, Weiss, Sara O., Brown, R. Dale, Perlov, Daniel, Ahmad, Hasan, Zhu, Peili, Greyson, Clifford, Long, Carlin S., and Schwartz, Gregory G.
- Subjects
- *
PEROXISOMES , *CORONARY disease , *HEART diseases , *LABORATORY swine , *BIOCHEMISTRY , *PHYSIOLOGY , *BIOLOGY - Abstract
Peroxisome proliferator-activated receptor (PPAR)-γ modulates substrate metabolism and inflammatory responses. In experimental rats subjected to myocardial ischemia-reperfusion (IR), thiazolidinedione PPAR-γ activators reduce infarct size and preserve left ventricular function. Troglitazone is the only PPAR-γ activator that has been shown to be protective in I/R in large animals. However, because troglitazone contains both α-tocopherol and thiazolidinedione moieties, whether PPAR-γ activation per se is protective in myocardial I/R in large animals remains uncertain. To address this question, 56 pigs were treated orally for 8 wk with troglitazone (75 mg·kg-1·day-1), rosiglitazone (3 mg·kg-1·day-1), or α-tocopherol (73 mg·kg-1·day-1, equimolar to troglitazone dose) or received no treatment. Pigs were then anesthetized and subjected to 90 min of low-flow regional myocardial ischemia and 90 min of reperfusion. Myocardial expression of PPAR-γ, determined by ribonuclease protection assay, increased with troglitazone and rosiglitazone compared with no treatment. Rosiglitazone had no significant effect on myocardial contractile function (FrankStarling relations), substrate uptake, or expression of proinflammatory cytokines during I/R compared with untreated pigs. In contrast, preservation of myocardial contractile function and lactate uptake were greater and cytokine expression was attenuated in pigs treated with troglitazone or α-tocopherol compared with untreated pigs. Multivariate analysis indicated that presence of an α-tocopherol, but not a thiazolidinedione, moiety in the test compound was significantly related to greater contractile function and lactate uptake and lower cytokine expression during I/R. We conclude that PPAR-γ activation is not protective in a porcine model of myocardial I/R. Protective effects of troglitazone are attributable to its α-tocopherol moiety. These findings, in conjunction with prior rat studies, suggest interspecies differences in the response to PPAR-γ activation in the heart. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
24. Endothelium-derived 2-arachidonylglycerol: an intermediate in vasodilatory eicosanoid release in bovine coronary arteries.
- Author
-
Gauthier, Kathryn M., Baewer, David V., Hittner, Sarah, Hillard, Cecilia J., Nithipatikom, Kasem, Reddy, D. Sudarshan, Falck, J. R., and Campbell, William B.
- Subjects
- *
CORONARY arteries , *ARTERIES , *HEART blood-vessels , *CYCLOOXYGENASES , *ENDOTHELIUM , *ACETYLCHOLINE , *BIOCHEMISTRY , *PHYSIOLOGY , *BIOLOGY - Abstract
Acetylcholine stimulates the release of endothelium-derived arachidonic acid (AA) metabolites including prostacyclin and epoxyeicosatrienoic acids (EETs), which relax coronary arteries. However, mechanisms of endothelial cell (EC AA activation remain undefined. We propose that 2-arachidonylglycerol (2-AG) plays an important role in this pathway. An AA metabolite isolated from bovine coronary ECs was identified as 2-AG by mass spectrometry. In ECs pretreated with the fatty acid amidohydrolase inhibitor diazomethylarachidonyl ketone (DAK; 20 μmol/l), methacholine (10 μmol/l)-stimulated 2-AG release was blocked by the phospholipase C inhibitor U-73122 (10 μmol/l) or the diacylglycerol lipase inhibitor RHC-80267 (40 μmol/l). In U-46619-preconstricted bovine coronary arterial rings, 2-AG relaxations averaging 100% at 10 μmol/l were inhibited by endothelium removal, by DAK, by the hydrolase inhibitor methyl arachidonylfluorophosphate (10 μmol/l), by the cyclooxygenase inhibitor indomethacin (10 μmol/l), but not by the CB1 cannabinoid receptor antagonist SR-141716 (1 μmol/l). The cytochrome P-450 inhibitor SKF-525a (10 μmol/l) and the 14,15-epoxyeicosa-5Z-enoic acid EET antagonist (14,15-EEZE; 10 μmol/l) further attenuated the indomethacin-resistant relaxations. The nonhydrolyzable 2-AG analogs noladin ether, 2-AG amide, and 14,15-EET glycerol amide did not induce relaxation. N-nitro-L-arginine-resistant relaxations to methacholine were also inhibited by U-73122, RHC-80267, and DAK. 14,15-EET glycerol ester increased opening of large-conductance K+ channels 12-fold in cell-attached patches of isolated smooth muscle cells and induced relaxations averaging 95%. These results suggest that methacholine stimulates EC 2-AG production through phospholipase C and diacylglycerol lipase activation. 2-AG is further hydrolyzed to AA, which is metabolized to vasoactive eicosanoids. These studies reveal a role for 2-AG in EC AA release and the regulation of coronary tone. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
25. Regulation of actin dynamics is critical for endothelial barrier functions.
- Author
-
Waschke, J., Curry, F. E., Adamson, R. H., and Drenckhahn, D.
- Subjects
- *
ACTOMYOSIN , *ACTIN , *ENDOTHELIUM , *CYTOCHALASINS , *CYTOSKELETON , *BIOCHEMISTRY , *PHYSIOLOGY , *BIOLOGY - Abstract
We tested the hypothesis that the equilibrium between F- and G-actin in endothetial cells modulates the integrity of the actin cytoskeleton and is important for the maintenance of endothelial barrier functions in vivo and in vitro. We used the actin-depolymerizing agent cytochalasin D and jasplakinolide, an actin filament (F-actin) stabilizing and promoting substance, to modulate the actin cytoskeleton. Low doses of jasplakinolide (0.1 μM. which we have previously shown to reduce the permeability-increasing effect of cytochalasin D, had no influence on resting permeability of single-perfused mesenteric microvessels in vivo as well as on monolayer integrity. The F-actin content of cultured endothelial cells remained unchanged. In contrast, higher doses (10 μM) of jasplakinolide increased permeability (hydraulic conductivity) to the same extent as cytochalasin D and induced formation of intercellular gaps in cultured myocardial endothelial (MyEnd) cell monolayers. This was accompanied by a 34% increase of F-actin and pronounced disorganization of the actin cytoskeleton in MyEnd cells. Furthermore, we tested whether an increase of cAMP by forskolin and rolipram would prevent the cytochalasin D-induced barrier breakdown. Conditions that increase intracellular cAMP failed to block the cytochalasin D-induced permeability increase in vivo and the reduction of vascular endothelial cadherin-mediated adhesion in vitro. Taken together, these data support the hypothesis that the state of polymerization of the actin cytoskeleton is critical for maintenance of endothelial barrier functions and that both depolymerization by cytochalasin D and hyperpolymerization of actin by jasplakinolide resulted in an increase of microvessel permeability in vivo. However, cAMP, which is known to support endothelial barrier functions, seems to work by mechanisms other than stabilizing F-actin. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
26. Nitric oxide donors protect murine myocardium against infarction via modulation of mitochondrial permeability transition.
- Author
-
Guangwu Wang, Liem, David A., Vondriska, Thomas M., Honda, Henry M., Korge, Paavo, Pantaleon, Dawn M., Xin Qiao, Wang, Yibin, Weiss, James N., and Ping, Peipei
- Subjects
- *
NITRIC oxide , *NITROGEN compounds , *CORONARY disease , *MITOCHONDRIA , *LABORATORY mice , *CYTOLOGY , *BIOCHEMISTRY , *PHYSIOLOGY , *BIOLOGY - Abstract
Mitochondrial permeability transition (MPT) pores have recently been implicated as a potential mediator of myocardial ischemic injury. Nitric oxide (NO) donors induce a poweful late phase of cardioprotection against ischemia-reperfusion injury; however, the cellular mechanisms involved are poorly understood. The role of MPT pores as a target of cardioprotective signaling pathways activated by NO has never been explored in detail. Thus mice were administered the NO donor diethylenetriamine (DETA)/NO (4 doses of 0.1 mg/kg iv each) 24 h before 30 min of coronary artery occlusion followed by 24 h of repeffusion. Infarct size was significantly reduced in DETA/NO-treated ngne (30 ± 2% of risk region in treated mice vs 50 ± 2% in control mice; P < 0.05), which demonstrates powerful cardioprotection. To examine the role of MPT pores, mice were administered atractyloside (Atr; 25 mg/kg iv), which induces adenine nucleotide translocase-dependent MPT, 20 min before ischemia. Atr blocked the infarct-sparing effects of DETA/NO (infarct size, 58 ± 1 vs, 30 ± 2% of risk region in DETA/NO; P < 0.05), whereas Atr alone had no effect. Mitochondria isolated from DETA/NO-treated mice exhibited increased resistance to Ca2+-thdueed swelling by 20 μmol/l CaCl2 or by the higher concentration of 200 μmol/l, which suggests that cardioprotection involves decreased propensity for MPT. Preincubation of mitochondria from control hearts with 30 nmol/l of the pore inhibitor cyclosporin A prevented swelling by 200 μmol/l CaCl2, thereby confirming that Ca2+ induces mitochondrial swelling via MPT. In accordance with the effects on infarct size, administration of Atr to the mice significantly abrogated DETA/NO-induced protection against Ca2+-induced mitochondrial swelling. These phenotypic alterations were associated with an increase in the antiapoptotic protein Bcl-2, which suggests that the underlying mechanisms may involve inhibition of cell death by Bcl-2. These data suggest that a critical process during NO donor-induced cardioprotection is to prevent MPT pore opening potentially via targeting of the adenine nucleotide translocator. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
27. Transpithelial HCO3- absorption is defective in renal thick ascending limbs from Na+/H+ exchanger NHE1 null mutant mice.
- Author
-
Good, David W., Watts III, Bruns A., George, Thampi, Meyer, Jamie W., and Shull, Gary E.
- Subjects
- *
BIOMOLECULES , *SODIUM compounds , *NEPHROLOGY , *BIOCHEMISTRY , *PHYSIOLOGY , *MOLECULAR biology , *BIOLOGY , *ANIMAL models in research - Abstract
In the medullary thick ascending limb (MTAL) of rat kidney, inhibiting basolateral Na+/H+ exchange with either amiloride or nerve growth factor (NGF) results secondarily in inhibition of apical Na+/H+ exchange, thereby decreasing transepithelial HCO3- absorption. To assess the possible role of the Na+/H+ exchanger NHE1 in this regulatory process, MTALs from wild-type and NHE1 knockout (NHE1-/-) mice were studied using in vitro microperfusion. The rate of HCO3- absorption was decreased 60% in NHE1-/- MTALs (15.4 ± 0.5 pmol·min-1·mm-1 wild-type vs. 6.0 ± 0.5 pmol·min-1·mm-1 NHE1-/-). Transepithelial voltage, an index of the NaCl absorption rate, did not differ in wild-type and NHE1-/- MTALs. Basolateral addition of 10 μM amiloride or 0.7 nM NGF decreased HCO3- absorption by 45–49% in wild-type MTALs but had no effect on HCO3- absorption in NHE1-/- MTALs. Inhibition of HCO3- absorption by vasopressin and stimulation by hyposmolality, both of which regulate MTAL HCO3- absorption through primary effects on apical Na+/H+ exchange, were similar in wild-type and NHE1-/- MTALs. Thus the regulatory defect in NHE1-/- MTALs is specific for factors (bath amiloride and NGF) shown previously to inhibit HCO3- absorption through primary effects on basolateral Na+/H+ exchange. These findings demonstrate a novel role for NHE 1 in transepithelial HCO3- absorption in the MTAL, in which basolateral NHE1 controls the activity of apical NHE3. Paradoxically, a reduction in NHE1-mediated H+ extrusion across the basolateral membrane leads to a decrease in apical Na+/H+ exchange activity that reduces HCO3- absorption. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
28. Activation of EP4 receptors contributes to prostaglandin E2-mediated stimulation of renal sensory nerves.
- Author
-
Kopp, Ulla C., Cicha, Michael Z., Nakamura, Kazuhiro, Nüsing, Rolf M., Smith, Lori A., and Hökfelt, Tomas
- Subjects
- *
PROSTAGLANDINS , *NEPHROLOGY , *BIOCHEMISTRY , *PHYSIOLOGY , *MOLECULAR biology , *BIOLOGY - Abstract
Induction of cyclooxygenase-2 (COX-2) in the renal pelvic wall increases prostaglandin E2 (PGE2) leading to stimulation of cAMP production, which results in substance P (SP) release and activation of renal mechanosensory nerves. The subtype of PGE receptors involved, EP2 and/or EP4, was studied by immunohistochemistry and renal pelvic administration of agonists and antagonists of EP2 and EP4 receptors. EP4 receptor-like immunoreactivity (LI) was colocalized with calcitonin gene-related peptide (CGRP)-LI in dorsal root ganglia (DRGs) at Th9-L1 and in nerve terminals in the renal pelvic wall. Th9-L1 DRG neurons also contained EP3 receptor-LI and COX-2-LI, each of which was colocalized with CGRP-LI in some neurons. No renal pelvic nerves contained EP3 receptor-LI and only very few nerves COX-2-LI. The EP1/EP2 receptor antagonist AH-6809 (20 μM) had no effect on SP release produced by PGE2 (0.14 μM) from an isolated rat renal pelvic wall preparation. However, the EP4 receptor antagonist L-161,982 (10 μM) blocked the SP release produced by the EP2/EP4 receptor agonist butaprost (10 μM) 12 ± 2 vs. 2 ± 1 and PGE2, 9 ± 1 vs. 1 ± 0 pg/min. The SP release by butaprost and PGE2 was similarly blocked by the EP4 receptor antagonist AH-23848 (30 μM). In anesthetized rats, the afferent renal nerve activity (ARNA) responses to butaprost 700 ± 100 and PGE2·780 ± 100%·s (area under the curve of ARNA vs. time) were unaffected by renal pelvic perfusion with AH-6809. However, 1 μM L-161,982 and 10 μM AH-23848 blocked the ARNA responses to butaprost by 94 ± 5 and 78 ± 10%, respectively, and to PGE2 by 74 ± 16 and 74 ± 11%, respectively. L-161,982 also blocked the ARNA response to increasing renal pelvic pressure 10 mmHg, 85 ± 5%. In conclusion, PGE2 increases renal pelvic release of SP and ARNA by activating EP4 receptors on renal sensory nerve fibers. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
29. Regulation of caspase-3 and -9 activation in oxidant stress to RTE by forkhead transcription factors, Bcl-2 proteins, and MAP kinases.
- Author
-
Kaushal, Gur P., Ling Liu, Kaushal, Varsha, Xiaoman Hong, Melnyk, Oksana, Seth, Rohit, Safirstein, Robert, and Shah, Sudhir V.
- Subjects
- *
BIOMOLECULES , *TRANSCRIPTION factors , *NEPHROLOGY , *BIOCHEMISTRY , *PHYSIOLOGY , *MOLECULAR biology , *BIOLOGY - Abstract
Cytotoxicity to renal tubular epithelial cells (RTE) is dependent on the relative response of cell survival and cell death signals triggered by the injury. Forkhead transcription factors, Bcl-2 family member Bad, and mitogen-activated protein kinases are regulated by phosphorylation that plays crucial roles in determining cell fate. We examined the role of phosphorylation of these proteins in regulation of H2O2-induced caspase activation in RTE. The phosphorylation of FKHR, FKHRL, and Bcl-2 family member Bad was markedly increased in response to oxidant injury, and this increase was associated with elevated levels of basal phosphorylation of Akt/protein kinase B. Phosphoinositol (PI) 3-kinase inhibitors abolished this phosphorylation and also decreased expression of antiapoptotic proteins Bcl-2 and BclxL. Inhibition of phosphorylation of forkhead proteins resulted in a marked increase in the proapoptotic protein Bim. These downstream effects of PI 3-kinase inhibition promoted the oxidant-induced activation of caspase-3 and -9, but not caspase-8 and -1. The impact of enhanced activation of caspases by PI 3-kinase inhibition was reflected on accelerated oxidant-induced cell death. Oxidant stress also induced marked phosphorylation of ERK1/2, P38, and JNK kinases. Inhibition of ERK1/2 phosphorylation but not P38 and JNK kinase increased caspase-3 and -9 activation; however, this activation was far less than induced by inhibition of Akt phosphorylation. Thus the Akt-mediated phosphorylation pathway, ERK signaling, and the anti-apoptotic Bcl-2 proteins distinctly regulate caspase activation during oxidant injury to RTE. These studies suggest that enhancing renal-specific survival signals may lead to preservation of renal function during oxidant injury. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
30. Renal damage progresses despite improvement of renal function after relief of unilateral ureteral obstruction in adult rats.
- Author
-
Keiichi Ito, Jie Chen, El Chaar, Maher, Stern, Joshua M., Seshan, Surya V., Khodadadian, Jonathan J., Richardson, Ingride, Hyman, Michael J., Vaughan Jr., E. Darracott, Poppas, Dix P., and Felsen, Diane
- Subjects
- *
NEPHROLOGY , *BIOCHEMISTRY , *PHYSIOLOGY , *MOLECULAR biology , *BIOLOGY , *ANIMAL models in research - Abstract
Progression of renal damage after relief of unilateral ureteral obstruction (UUO) has been demonstrated, especially in neonatal rats. We evaluated renal function and renal damage after relief of 3-day UUO in five groups of adult rats: group 1, no treatment; group 2, 3-day UUO; groups 3–5, 3-day UUO followed by relief; group 3, 7-day relief; group 4, 14-day relief; and group 5, 28-day relief. Glomerular filtration rate (GFR), renal blood flow (RBF), tissue transforming growth factor-β (TGF-β), interstitial fibrosis and fibroblast expression, tubular apoptosis, macrophage infiltration, expression of nitric oxide synthases (NOS), and urinary nitrate/nitrite (NO2/NO3) were evaluated. RBF and GFR were decreased to <10% of baseline by 3 days of UUO. GFR and RBF in a previously obstructed kidney (POK) returned to baseline by 14 days after relief. Both tissue TGF-β1 and interstitial fibrosis were significantly higher in POK of groups 3–5 compared with groups 1 and 2. In group 5, the numbers of infiltrating macrophages, fibroblasts, and apoptotic tubular cells were higher in POK compared with group 1. Urinary NO2/NO3 was significantly higher than baseline from 3 to 27 days after relief of UUO. Expression of NOS isoforms was increased in tubules. As interstitial fibrosis contributes to decreased renal function, these results suggest that the acute recovery in function may be compromised in the long term by the progressive renal fibrosis which was found. Furthermore, pharmacological intervention at the time of relief of UUO, targeted to fibrotic processes, may contribute to long-term recovery of renal function. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
31. Cell density-dependent expression of EDG family receptors and mesangial cell proliferation: role in lysophosphatidic acid-mediated cell growth.
- Author
-
Yiding Xing, Ganji, Shobha H., Noh, Jung W., and Kamanna, Vaijinath S.
- Subjects
- *
LYSOPHOSPHOLIPIDS , *CYTOLOGY , *NEPHROLOGY , *CELL growth , *BIOCHEMISTRY , *PHYSIOLOGY , *MOLECULAR biology , *BIOLOGY - Abstract
Lysophosphatidic acid (LPA), a major member of the bioactive lysophospholipids in serum, possesses diverse physiological activities including cell proliferation. Recently, three endothelial differentiation gene (EDG) family receptors, including EDG-2 (LPA1), EDG-4 (LPA2), and EDG-7 (LPA3), have been identified as LPA receptors. The role of LPA and their receptors in mesangial cell physiology is not clearly understood. This study examined the expression profile of EDG receptors as a function of cell density and the participation of EDG receptors in human mesangial cell proliferation by LPA. We showed that mesangial cells express all three EDG family LPA receptors in a cell density-dependent manner. EDG-7 maximally expressed at sparse cell density and minimally expressed in dense cell population. The EDG-2 expression pattern was opposite to the EDG-7. No changes in EDG-4 expression as a function of cell density were noted. DNA synthetic rate was greater in sparse cell density compared with dense cell population and followed a similar pattern with EDG-7 expression. Comparative studies in sparse and dense cell density indicated that EDG-7 was positively associated, whereas EDG-2 was negatively associated with cell proliferation rate. LPA induced mesangial cell proliferation by 1.5- to 3.5-fold. Dioctanoylglycerol pyrophosphate, an antagonist for EDG-7, almost completely inhibited mesangial cell proliferation induced by LPA. We suggest that EDG-7 regulates LPA-mediated mesangial cell proliferation. Additionally, these data suggest that EDG-7 and EDG-2 LPA receptors play a diverse role as proliferative and antiproliferative, respectively, in mesangial cells. Regulation of EDG family receptors may be importantly linked to mesangial cell-proliferative processes. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
32. Determinants of basal nitric oxide concentration in the renal medullary microcirculation.
- Author
-
Wensheng Zhang, Pibulsonggram, Tosapol, and Edwards, Aurélie
- Subjects
- *
NITROGEN compounds , *NITRIC oxide , *BIOCHEMISTRY , *BIOMOLECULES , *NEPHROLOGY , *PHYSIOLOGY , *MOLECULAR biology , *BIOLOGY - Abstract
In this study, we modeled the production, transport, and consumption of nitric oxide (NO) in the renal medullary microcirculation under basal conditions. To yield agreement with reported NO concentrations of ∼60–140 nM in medullary tissues (Zou AP and Cowley AW Jr. Hypertension 29: 194–198, 1997; Am J Physiol Regul Integr Comp Physiol 279: R769–R777, 2000) and 3 nM in plasma (Stamler JS, Jaraki O, Osborne J, Simon DI, Keaney J, Vita J, Singel D, Valeri CR, and Loscalzo J. Proc Natl Acad Sci USA 89: 7674–7677, 1992), the permeabilities of red blood cells (RBCs), vascular walls, and pericytes to NO are all predicted to lie between 0.01 and 0.1 cm/s, and the NO production rate by vasa recta endothelium is estimated to be on the order of 10–14 μmol · μm-2 · s-1. Our results suggest that the concentration of NO in RBCs, which is essentially controlled by the kinetics of NO scavenging by hemoglobin, is ∼0.01 nM, that is, 10³ times lower than that in plasma, pericytes, and interstitium. Because the basal concentration of NO in pericytes is on the order of 10 nM, it may be too low to active guanylate cyclase, i.e., to induce vasorelaxation. Our simulations also indicate that basal superoxide concentrations may be too low to affect medullary NO levels but that, under pathological conditions, superoxide may be a very significant scavenger of NO. We also found that although oxygen is a negligible NO scavenger, medullary hypoxia may significantly enhance NO concentration gradients along the corticomedullary axis. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
33. Hypoxic induction of Ctgf is directly mediated by Hif-1.
- Author
-
Higgins, Debra F., Biju, Mangatt P., Akai, Yasuhiro, Wutz, Anton, Johnson, Randall S., and Haase, Volker H.
- Subjects
- *
BIOMOLECULES , *NEPHROLOGY , *BIOCHEMISTRY , *PHYSIOLOGY , *MOLECULAR biology , *BIOLOGY - Abstract
CTGF plays a significant role in the development of renal fibrosis by mediating the fibrotic effects of transforming growth factor (TGF)-β1 and has been shown to be hypoxia inducible in human breast cancer cells. It has been suggested that hypoxia is an important underlying cause for the development of renal fibrosis through the modulation of profibrotic genes. One of the key mediators of the cell's response to lowered oxygen environments is hypoxia-inducible-factor-1 (HIF-1), a basic helix-loop-helix transcription factor, which enables cells to adapt to hypoxia by regulating the expression of genes involved in increasing oxygen availability (VEGF, erythropoietin) and enhancing glucose uptake and metabolism (Glut-1, PGK). In this paper, we have used primary tubular epithelial cell cultures from a tetracycline-inducible-Hif-1α knockout murine model to further elucidate the role of Hif-1 in the hypoxic-induction of Ctgf expression. We show that hypoxia response elements present upstream of Ctgf enable direct interaction of Hif-1 transcription factor with the Ctgf promoter, resulting in increased transcription of Ctgf mRNA. Cells deficient in Hif-1α were incapable of inducing Ctgf mRNA in response to hypoxia, suggesting an absolute requirement of Hif-1. Furthermore, the observed Hif-1-mediated hypoxic stimulation of Ctgf expression was found to occur independently of TGF-β1 signaling. Our findings have important implications for a number of fibrotic disorders in which hypoxia, CTGF, and TGF-β1 are involved, including renal, dermal, hepatic, and pulmonary fibrosis. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
34. Inhibition of K conductance in descending vasa recta pericytes by ANG II.
- Author
-
Pallone, Thomas L., Chunhua Cao, and Zhong Zhang
- Subjects
- *
POTASSIUM , *ANGIOTENSINS , *ANGIOTENSIN II , *NEPHROLOGY , *BIOCHEMISTRY , *PHYSIOLOGY , *MOLECULAR biology , *BIOLOGY - Abstract
We tested whether K+ channel inhibition accompanies ANG II-induced depolarization of descending vasa recta (DVR) pericytes. An increase in extracellular K+ concentration ([K+]o) from 5 to 100 mM depolarized resting pericytes but had no effect after prolonged (10 nM, 20 min) ANG II exposure. In contrast, reduction of extracellular Cl- concentration ([Cl-]o) from 154 to 34 mM had a minor effect on resting membrane potential but strongly depolarized pericytes treated with ANG II. The K+ channel blockers BaCl2 (0.1, 1 mM) and tetraethylammonium (TEA; 30 mM) depolarized resting pericytes but did not affect membrane potential of ANG II-treated pericytes. Pericyte whole cell currents were reduced by ANG II and nearly eliminated by combined ANG II exposure and the Cl- channel blocker niflumic acid (100 &mul;M). Augmentation of inward current induced by raising [K+]o from 5 to 50 mM was eliminated by preexposure to ANG II. TEA- and BaCl2-sensitive outward currents, generated by depolarizing pericytes from -80 to -40 mV, were eliminated by ANG II. We conclude that ANG II depolarizes DVR pericytes by a combination of Cl- channel activation and K+ channel inhibition. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
35. Effects of dietary fat, NaCl, and fructose on renal sodium and water transporter abundances and systemic blood pressure.
- Author
-
Jian Song, Xinquin Hu, Min Shi, Knepper, Mark A., and Ecelbarger, Carolyn A.
- Subjects
- *
SODIUM phosphates , *NEPHROLOGY , *BIOCHEMISTRY , *PHYSIOLOGY , *MOLECULAR biology , *BIOLOGY - Abstract
Dietary fructose, NaCl, and/or saturated fat have been correlated with mean arterial pressure (MAP) rises in sensitive strains of rats. Dysregulation of sodium and/or water reabsorption by the kidney may contribute. Using radiotelemetry and parallel semiquantitative immunoblotting, we examined the effects of various diets on MAP and the regulation of abundance of the major renal sodium and water transport proteins in male SpragueDawley rats. In study 1, rats (∼275 g) were fed one of four diets for 4 wk (n = 6/group): 1) control, 2) 65% fructose, 3) control + added NaCl (2.59%), or 4) fructose + NaCl. In study 2, 5% butter (fat) was added to the above four diets. Both fat and NaCl, but not fructose, caused modest rises in MAP (5–10 mmHg) and increased the day-to-night ratio in diastolic blood pressure. NaCl or fructose increased kidney size. Creatinine clearance was increased by salt or fat, and fractional excretion of sodium was decreased by fat. In study 1, high NaCl markedly reduced plasma renin and aldosterone and its regulated proteins in whole kidney, i.e., the thiazide-sensitive Na-Cl cotransporter and the α- and γ (70-kDa band)-subunits of the epithelial sodium channel. These effects were blunted by fat. Fructose increased the abundance of the sodium phosphate cotransporter, whereas it decreased the bumetanide-sensitive Na-K-2Cl cotransporter and aquaporin-2. Overall, doubling of dietary fat appeared to impair dietary sodium adaptation, i.e., blunt the downregulation of aldosterone-mediated effects, thus allowing blood pressure to rise at an accelerated rate. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
36. Heterogeneous distribution of chloride channels along the distal convoluted tubule probed by single-cell RT-PCR and patch clamp.
- Author
-
Nissant, Antoine, Lourdel, Stéphanie, Baillet, Sophie, Paulais, Marc, Marvao, Pedro, Teulon, Jacques, and Imbert-Teboul, Martine
- Subjects
- *
BIOMOLECULES , *ION channels , *CHLORIDE channels , *NEPHROLOGY , *BIOCHEMISTRY , *PHYSIOLOGY , *MOLECULAR biology , *BIOLOGY - Abstract
The distal convoluted tubule (DCT) is a heterogeneous segment subdivided into early (DCT1) and late (DCT2) parts, depending on the distribution of various transport systems. We do not have an exhaustive picture of the Cl- channels on the basolateral side: the presence of ClC-K2 channels is generally accepted, whereas that of ClC-K1 remains controversial. We used here single-cell RT-PCR and patch clamp to probe Cl- channel heterogeneity in microdissected mouse DCT at the molecular and functional levels. Our findings show that 63% of the DCT cells express ClC-K2 mRNA, either alone (type 1 cells: 47 and 23% in DCT1 and DCT2, respectively), or combined with ClC-K1, mostly in DCT2 (type 2 cells: 33%), but 37% of DCT1 and DCT2 cells do not express any ClC-K. Patch-clamp experiments revealed that a Cl- channel, with 9-pS conductance and Cl- > NO3- = Br- anion selectivity sequence, is present in the DCT1 and DCT2 basolateral membranes (87 and 71% of the patches, respectively). This dominant channel is likely to be ClC-K2 in type 1 cells. In type 2 cells, it could be ClC-K2 and/or ClC-K1 homodimers, but also ClC-K1/ClC-K2 heterodimers, or a mixture of all combinations. A second, distinct Cl- channel (13% of DCT1 patches, 29% of DCT2 patches) also displayed 9-pS conductance but had a completely different anion selectivity (I- > NO3- > Br- > Cl-), which was not compatible with that of the ClC-Ks. This indicates that a Cl- channel that is unlikely to belong to the ClC family may also be involved in Cl- absorption in the DCT2. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
37. The Cl-/HCO3- exchanger pendrin in the rat kidney is regulated in response to chronic alterations in chloride balance.
- Author
-
Quentin, Fabienne, Chambrey, Régine, Trinh-Trang-Tan, Marie Marcelle, Fysekidis, Marinos, Cambillau, Michèle, Paillard, Michel, Aronson, Peter S., and Eladari, Dominique
- Subjects
- *
BIOCHEMISTRY , *BIOMOLECULES , *NEPHROLOGY , *PHYSIOLOGY , *MOLECULAR biology , *BIOLOGY - Abstract
Pendrin (Pds; Slc26A4) is a new anion exchanger that is believed to mediate apical Cl-/HCO3- exchange in type B and non-A-non-B intercalated cells of the connecting tubule and cortical collecting duct. Recently, it has been proposed that this transporter may be involved in NaCl balance and blood pressure regulation in addition to its participation in the regulation of acid-base status. The purpose of our study was to determine the regulation of Pds protein abundance during chronic changes in chloride balance. Rats were subjected to either NaCl, NH4Cl, NaHCO3, KCl, or KHCO3 loading for 6 days or to a low-NaCl diet or chronic furosemide administration. Pds protein abundance was estimated by semi-quantitative immunoblotting in renal membrane fractions isolated from the cortex of treated and control rats. We observed a consistent inverse relationship between Pds expression and diet-induced changes in chloride excretion independent of the administered cation. Conversely, NaCl depletion induced by furosemide was associated with increased Pds expression. We conclude that Pds expression is specifically regulated in response to changes in chloride balance. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
38. Effect of thiazide on renal gene expression of apical calcium channels and calbindins.
- Author
-
Chien-Te Lee, Shuhua Shang, Li-Wen Lai, Kim-Chong Yong, and Lien, Yeong-Hau H.
- Subjects
- *
CALCIUM channels , *CYTOLOGY , *BIOCHEMISTRY , *BIOMOLECULES , *NEPHROLOGY , *PHYSIOLOGY , *MOLECULAR biology , *BIOLOGY - Abstract
Thiazide diuretics are specific inhibitors of the Na-Cl cotransporter in the distal convoluted tubule (DCT). In addition to producing diuresis and natriuresis, they have a hypocalciuric effect. Recently, two apical calcium channels have been identified, transient receptor potential vanilloid 5 (TRPV5) and TRPV6; both are expressed in the DCT. We studied the effects of thiazides on mouse renal calcium handling and renal gene expression of TRPV5 and TRPV6, as well as calbindin-D28k and calbindin-D9k, both of which are calcium transport facilitators located in the DCT. Upregulation of renal TRPV5 was found 4 h after intraperitoneal injection of chlorothiazide (CTZ) at both 25 and 50 mg/kg, but not at 100 mg/kg. Chronic treatment with CTZ at 25 mg/kg twice daily for 3 days, with or without salt supplementation of 0.8% NaCl and 0.1% KCl in the drinking water, caused hypocalciuria, but the gene expression patterns were different. Without salt supplementation, mice developed volume contraction and there were no changes in gene expression. When volume contraction was prevented by salt supplementation, there was a significant increase in gene expression of TRPV5, calbindin-D28k, and calbindin-D9k. Salt supplementation alone also induced significant upregulation of TRPV5, TRPV6, and both calbindins. The upregulation of TRPV5 by CTZ and salt supplementation and salt alone was further confirmed with immunofluorescent staining studies. Our studies suggest that thiazides induce hypocalciuria through different mechanisms depending on volume status. With volume contraction, increased calcium reabsorption in the proximal tubule plays the major role. Without volume contraction, hypocalciuria is probably achieved through increased calcium reabsorption in the DCT by the activation of a transcellular calcium transport system and upregulation of apical calcium channel TRPV5, calbindin-D28k, and calbindin-D9k. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
39. Effect of endogenous angiotensin II on the frequency response of the renal vasculature.
- Author
-
DiBona, Gerald F. and Sawin, Linda L.
- Subjects
- *
ANGIOTENSINS , *ANGIOTENSIN II , *BIOCHEMISTRY , *BIOMOLECULES , *NEPHROLOGY , *PHYSIOLOGY , *MOLECULAR biology , *BIOLOGY - Abstract
The renal vasculature functions as an efficient low-pass filter of the multiple frequencies contained within renal sympathetic nerve activity. This study examined the effect of angiotensin II on the frequency response of the renal vasculature. Physiological changes in the activity of the endogenous renin-angiotensin system were produced by alterations in dietary sodium intake. The frequency response of the renal vasculature was evaluated using pseudorandom binary sequence renal nerve stimulation, and the role of angiotensin II was evaluated by the administration of the angiotensin II AT1-receptor antagonist losartan. In low-sodium-diet rats with increased renin-angiotensin system activity, losartan steepened the renal vascular frequency response (i.e., greater attenuation); this was not seen in normal- or high-sodium-diet rats with normal or decreased renin-angiotensin system activity. Analysis of the transfer function from arterial pressure to renal blood flow, i.e., dynamic autoregulation, showed that the tubuloglomerular feedback but not the myogenic component was enhanced in low- and normal- but not in high-sodium-diet rats and that this was reversed by losartan administration. Thus physiological increases in endogenous renin-angiotensin activity inhibit the renal vascular frequency response to renal nerve stimulation while selectively enhancing the tubuloglomerular feedback component of dynamic autoregulation of renal blood flow. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
40. Alterations in cell-adhesive and migratory properties of proximal tubule and collecting duct cells from bc1-2 -/- mice.
- Author
-
Ziehr, Jacqueline, Sheibani, Nader, and Sorenson, Christine M.
- Subjects
- *
CYTOLOGY , *CELL adhesion , *APOPTOSIS , *BIOCHEMISTRY , *BIOMOLECULES , *NEPHROLOGY , *PHYSIOLOGY , *MOLECULAR biology , *BIOLOGY - Abstract
Bc1-2 protects cells from apoptosis initiated by a variety of stimuli including loss of cell adhesion. Bc1-2 -/- mice develop renal hypoplastic/cystic dysplasia with renal cyst formation coinciding with renal maturation in normal mice. To gain a better understanding of the role cell-adhesive mechanisms play during renal maturation, we generated proximal tubule and collecting duct cell lines from postnatal day 10 (P10) and P20 bc1-2 +/+ and bcl-2 -/- mice. Very little is known about the role cell-adhesive and migratory mechanisms play during renal maturation. We observed that modulation of cell-adhesive properties, which normally occur in a nephron segment-specific manner during renal maturation, and cell migration were altered in cells from bc1-2 -/- mice. Enhanced migration of bc1-2 -/- proximal tubule cells in a scratch wound assay was completely inhibited by incubation with PP1 (Src inhibitor) and moderately affected by incubation with SB-203580 (p38 inhibitor). These cells expressed increased levels of fibronectin and had numerous central focal adhesions. P20 bc1-2 -/- proximal tubule cells adhered to fibronectin but adhered poorly to collagen, vitronectin, or laminin. Collecting duct cells, similar to proximal tubule cells from bc1-2 -/- mice, demonstrated enhanced migration in a scratch wound assay that was inhibited by incubation with PP1. Migration of these cells was moderately affected by incubation with PD-98059 (MEK inhibitor) or LY-294002 (PI3 kinase inhibitor), whereas incubation with SB-203580 had no effect. P10 bc1-2 -/- collecting duct cells also expressed increased levels of fibronectin but decreased levels of thrombospondin-1 and demonstrated precocious binding to fibronectin and vitronectin compared with bc1-2 +/+ cells. The ability of P20 bc1-2 +/+ collecting duct cells to adhere to fibronectin and vitronectin corresponded with a decline in thrombospondin-1 expression. Therefore, alterations in cell-adhesive and migratory characteristics may be an early indicator of aberrant renal epithelial cell differentiation. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
41. PDZ binding motif-dependent localization of K+ channel on the basolateral side in distal tubules.
- Author
-
Tanemoto, Masayuki, Abe, Takaaki, Onogawa, Tohru, and Ito, Sadayoshi
- Subjects
- *
BIOCHEMISTRY , *BIOMOLECULES , *NEPHROLOGY , *PHYSIOLOGY , *MOLECULAR biology , *BIOLOGY - Abstract
Kir5.1, a nonfunctional inwardly rectifying K+ channel by itself, can form functional channels by assembling with other proteins. We previously showed that Kir5.1 assembled with Kir4.1 and functioned as an acid-base regulator in the kidney. In this study, we examined the intrarenal distribution of Kir5.1 by RT-PCR analysis on dissected nephron segments and immunohistochemical analysis with the specific anti-Kir5.1 antibody. Strong expression of Kir5.1 was detected in distal convoluted tubules, and weak expression was also detected in thick ascending limb of Henle's loop. Colocalization of Kir5.1 with Kir4.1 indicated expression of Kir5.1/Kir4.1 heteromer in these nephron segments. In a renal epithelial cell line, MadinDarby canine kidney cells, heteromer formation with Kir4.1 changed the localization of Kir5.1 from intracellular components to the cell surface. The COOH-terminal cytoplasmic portion that includes the PDZ binding motif of Kir4.1 was responsible for this intracellular localization. These data suggest the signals on the COOH terminus of Kir4.1, including PDZ binding motif, determine the intracellular localization of Kir5.1/Kir4.1 heteromer in distal tubules. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
42. Effect of low-protein diet and protein supplementation on the expressions of TNF-α, TNFR-I, and TNFR-II in organs and muscle of LPS-injected rats.
- Author
-
Raina, Nilima and Jeejeebhoy, Khursheed N.
- Subjects
- *
METABOLISM , *PHYSIOLOGY , *BIOCHEMISTRY , *TUMOR necrosis factors , *PROTEINS , *ORGANIC compounds - Abstract
Previous studies had shown that increasing energy intake in anorexic TNF-α-treated rats increased morbidity due to stabilization of TNF activity by soluble and membrane TNF receptors (TNFR). Although protein supplementation reduces septic morbidity, its effect on TNF and TNFR is unknown. To determine the effect of low protein intake and supplementation on TNF and TNFR, 30 male Wistar rats weighing 250 g were fed a liquid defined-formula diet for 10 days and randomly allocated to 1) controls (C; n = 6), receiving normal energy and protein energy density of 0.047 MJ/60 ml + normal saline (NS); 2) low protein (LP; n = 6), receiving normal energy but a reduced protein-energy density of 0.012 MJ/60 ml + LPS; 3) refeeding (RF; n = 6), initially depleted on low-protein diet (10 days) and then repleted on normal protein (10 days) while receiving LPS; and 4) pair fed (P-F; n = 12), individual P-F rats being paired with individual LP or RF rats receiving NS. Protein and mRNA expression of TNF-α, TNFR-I, and TNFR-II in liver, spleen, and gastrocnemius were measured by Western blot and RT-PCR, respectively. In liver, the changes in TNF-α, TNFR-I, and TNFR-II were translational, whereas in spleen the effects were due to a combination of transcription and translation. In gastrocnemius, the effects were transcriptional/translational for TNFRs. In contrast, TNF-α mRNA was significantly increased, but TNF-α protein expression was reduced in LP rats compared with C and RF groups. In conclusion, protein deficiency in endotoxic rats increases the expression of TNFR-I and TNFR-II in all organs studied and TNF-α in selected ones. This increase is suppressed by refeeding protein. A differential pattern between translation and transcription of TNF-α and its receptors is present. Our data suggest that protein restriction may be deleterious in sepsis. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
43. Forearm vascular control during acute hyperglycemia in healthy humans.
- Author
-
Reed, Ann S., Charkoudian, Nisha, Vella, Adrian, Pankaj Shah, Rizza, Robert A., and Joyner, Michael J.
- Subjects
- *
PHYSIOLOGY , *HYPERGLYCEMIA , *BLOOD sugar , *ENDOCRINOLOGY , *METABOLISM , *BIOCHEMISTRY - Abstract
The vascular endothelium is a site of pathological changes in patients with diabetes mellitus that may be related to severe chronic hyperglycemia. However, it is unclear whether transient hyperglycemia alters vascular function in an otherwise healthy human forearm. To test the hypothesis that acute, moderate hyperglycemia impairs endothelium-dependent forearm vasodilation, we measured vasodilator responses in 25 healthy volunteers (11 F, 14 M) assigned to one of three protocols. In protocol 1, glucose was varied to mimic a postprandial pattern (i.e., peak glucose ∼11.1 mmol/1) commonly observed in individuals with impaired glucose tolerance. Protocol 2 involved 6 h of mild hyperglycemia (∼7 mmol/l). Protocol 3 involved 6 h of euglycemia. Glucose concentration was maintained with a variable systemic glucose infusion. Insulin concentrations were maintained at ∼65 pmol/l by means of a somatostatin and "basal" insulin infusion. Glucagon and growth hormone were replaced at basal concentrations. Forearm blood flow (FBF) was calculated from Doppler ultrasound measurements at the brachial artery. In each protocol, FBF dose responses to intrabrachial acetylcholine (ACh) and sodium nitroprusside (NTP) were assessed at baseline and at 60, 180, and 360 min of glucose infusion. Peak endothelium-dependent vasodilator responses to ACh were not diminished by hyperglycemia in any trial. For example, peak responses to ACh during protocol 2 were 307 ± 47 ml/min at euglycemic baseline and 325 ± 52, 353 ± 65, and 370 ± 70 ml/min during three subsequent hyperglycemic trials (P = 0.46). Peak endothelium-independent responses to NTP infusion were also unaffected. We conclude that acute, moderate hyperglycemia does not cause short-term impairment of endothelial function in the healthy human forearm. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
44. Heteromeric amino acid transporters: biochemistry, genetics, and physiology.
- Author
-
Chillaron, Josep, Roca, Ramon, Valencia, Alfonso, Zorzano, Antonio, and Palacin, Manuel
- Subjects
- *
AMINO acids , *BIOCHEMISTRY , *GENETICS , *PHYSIOLOGY - Abstract
Examines the biochemical, genetic and physiological aspects of heteromeric amino acid transporters (HAT). Investigation on the polypeptide composition of HAT; Comparison between heavy and light subunit HAT; Representation of the classic mammalian amino acid transport systems.
- Published
- 2001
- Full Text
- View/download PDF
45. A Midlecture Student Seminar: an Activity to Break the Monotony.
- Author
-
Rao, Mohandas
- Subjects
- *
MEDICAL schools , *UNIVERSITIES & colleges , *MEDICAL education , *MEDICAL students , *ANATOMY , *PHYSIOLOGY , *BIOCHEMISTRY ,STUDY & teaching of medicine - Abstract
The article reports that students at Melaka Manipal Medical College have undergone their first 2.5 year of a medical training program in Malaysia. Students are taught anatomy, physiology, and biochemistry. The anatomy classes include both small-group cadaveric dissection sessions and large-group lecture classes of 1 hour each. In an effort to break the monotomy and to engage the students in active learning, a midlecture student seminar is conducted. The midlecture student seminar consists of two parts, a short presentation by students, followed by postpresentation discussions.
- Published
- 2006
- Full Text
- View/download PDF
46. MERIT-BASED REARRANGEMENT OF STUDENTS FOR BETTER INTERACTIONS.
- Author
-
Nayak, Satheesha, Ramnarayan, K., and Somayaji, S. N.
- Subjects
- *
CURRICULUM , *INSTRUCTIONAL systems , *INTERDISCIPLINARY education , *PHYSIOLOGY , *ANATOMY , *BIOCHEMISTRY , *EVALUATION , *UNIVERSITIES & colleges - Abstract
The article reports on the integrated curriculum at Melaka Manipal Medical College in India. Students joined this program after completing high school. In the first year, the students learned the subjects Anatomy, Physiology, and Biochemistry. The curriculum includes lecturers, practical classes, and tutorials. The students were rearranged according to their academic performance. The academically weak students were encouraged to interact with their group members and to dissect the cadaver. The redistribution helped these students to overcome their reluctance to answer questions during the tutorials.
- Published
- 2005
- Full Text
- View/download PDF
47. Announcements.
- Subjects
- *
AWARDS , *PHYSIOLOGY , *BIOCHEMISTRY - Abstract
Announces the recipient of the 2003 Nobel Prize in Chemistry. Name of the awardee; Recognition of research on renal physiology; Significance of the award.
- Published
- 2004
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.