Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P21817 (RyR1)
 1,154 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies indicate that angiotensin II (ANG II) plays a minor role in the hemodynamic responses during dynamic exercise. However, nonspecific effects associated with methods used to block its production [e.g., angiotensin-converting enzyme (ACE) inhibitors] or receptors (e.g., saralasin) may have contributed to these findings. Losartan is a nonpeptide ANG II receptor antagonist that is devoid of such nonspecific effects. We hypothesized that the contribution of ANG II to the cardiovascular response to dynamic exercise is characterized more precisely with losartan than with saralasin. On separate days, 6 miniswine performed treadmill running at 80% of their maximal heart rate (HR) reserve (HRR) in the presence of vehicle (0.9% saline), saralasin (10 or 20 micrograms/kg/min intraleft arterially, i.a.), or losartan (15 or 20 mg/kg i.a.). Cardiac output (CO), HR, and myocardial contractility were similar among all exercise conditions. As compared with the vehicle, losartan decreased mean arterial pressure (MAP) and systemic vascular resistance (SVR) during exercise, whereas no differences occurred between the vehicle and saralasin conditions. Both receptor antagonists increased blood flow and/or decreased vascular resistance during exercise in the myocardium, stomach, small intestine, and colon. As compared with that during treadmill running with vehicle infusion, renal blood flow (RBF) was increased by losartan and decreased by saralasin. We conclude that the contribution of ANG II to the cardiovascular response to dynamic exercise is demonstrated more clearly with losartan than with saralasin.
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PMID:Effects of angiotensin II receptor blockade during exercise: comparison of losartan and saralasin. 885 77

Recently, a receptor for renin was described that may be important for vascular uptake and activation of (pro)renin, thus leading to local generation of angiotensin II. To assess the in vivo relevance of this protein, we generated transgenic rats overexpressing the human renin receptor gene in smooth muscle tissue, under the control of a 16-kb fragment of the mouse smooth muscle myosin heavy chain gene [TGR(SMMHC-HRR)]. Four lines of transgenic animals were obtained. The correct pattern of expression of the transgene was confirmed by RNase protection assay and in situ hybridization. TGR(SMMHC-HRR) rats are fertile and develop normally. After 6 months of age, transgenic rats develop a cardiovascular phenotype with an elevated systolic blood pressure (137.8+/-5 versus 118.9+/-3.7 mm Hg; P=0.008), and an augmentation in heart rate (349.1+/-7.7 versus 303.1+/-16.16 bpm; P=0.023) in TGR(SMMHC-HRR) and controls, respectively. These alterations are progressively increasing with aging. Although kidney function and plasma renin were normal in TGR(SMMHC-HRR), an increase in plasma aldosterone [TGR(SMMHC-HRR) 428+/-64.9 versus 207.3+/-73.24 pg/mL in control; P=0.02] and in aldosterone/renin ratio [TGR(SMMHC-HRR) 8.04+/-2.2 versus 2.8+/-0.55 in control; P=0.03] was observed. This suggests that renin receptor overexpression has resulted in increased intraadrenal angiotensin II, thereby provoking enhanced aldosterone generation in the absence of changes in plasma renin. The rise in aldosterone may underlie, at least in part, the observed cardiovascular phenotype of TGR(SMMHC-HRR).
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PMID:Elevated blood pressure and heart rate in human renin receptor transgenic rats. 1640 65