Simvastatin Acts Synergistically with ACE Inhibitors or Amlodipine to Decrease Oxygen Consumption in Rat Hearts

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Abstract
Statin drugs, which are cholesterol-lowering agents, can upregulate endothelial nitric oxide synthase (eNOS) in isolated endothelial cells independent of lipid lowering. We investigated the effect of short-term simvastatin administration on NO-mediated regulation of myocardial oxygen consumption (MVO2) in tissue from rat hearts. Male Wistar rats were divided into (a) control group (n = 14), and (b) simvastatin group (n = 10, 20 mg/kg/day by oral gavage). After 2 weeks, left ventricular myocardium was isolated to measure MVO2 using a Clark-type oxygen electrode, and aortic plasma nitrates and nitrites (NOx) were measured. Baseline plasma NOx levels (19 ± 2.6 in control vs. 20 ± 2.5 μM/L in simvastatin) and baseline MVO2 (288 ± 23 in control vs. 252 ± 11 nmol/g/min; p = 0.09) were not significantly different between the two groups. NO-dependent regulation of MVO2 in response to bradykinin, ramipril, or amlodipine was augmented in simvastatin rats compared with controls (p 2