Simvastatin acts synergistically with ACE inhibitors or amlodipine to decrease oxygen consumption in rat hearts.

摘要: Statin drugs, which are cholesterol-lowering agents, can upregulate endothelial nitric oxide synthase (eNOS) in isolated cells independent of lipid lowering. We investigated the effect short-term simvastatin administration on NO-mediated regulation myocardial oxygen consumption (MV(O2)) tissue from rat hearts. Male Wistar rats were divided into (a) control group (n = 14), and (b) 10, 20 mg/kg/day by oral gavage). After 2 weeks, left ventricular myocardium was to measure MV(O2) using a Clark-type electrode, aortic plasma nitrates nitrites (NOx) measured. Baseline NOx levels (19+/-2.6 vs. 20+/-2.5 microM/L simvastatin) baseline (288+/-23 252+/-11 nmol/g/min; p 0.09) not significantly different between two groups. NO-dependent response bradykinin, ramipril, or amlodipine augmented compared with controls (p < 0.05). Decrease highest doses versus groups as follows-bradykinin, -28+/-5% -44+/-6%; -35+/-5% -50+/-8%; amlodipine, -32+/-9% -42+/-3%. Response dose NO donor S-nitroso N-acetyl penicillamine (SNAP) (-55+/-5% -52+/-7%). Treatment Nw-nitro-L-arginine methyl ester, inhibitor synthesis, attenuated In conclusion, potentiates ability angiotensin-converting enzyme (ACE) inhibitors cause MV(O2).