Asymmetric Dimethylarginine Determines the Improvement of Endothelium-Dependent Vasodilation by Simvastatin: Effect of Combination With Oral L-Arginine

摘要: Objectives We hypothesized that the level of asymmetric dimethylarginine (ADMA), an endogenous inhibitor endothelial nitric oxide (NO) synthase (eNOS), might determine effects statins. Background Endothelial NO is up-regulated by However, statins failed to improve function in some studies. Asymmetric inhibits eNOS a mechanism reversible L-arginine. Methods Ninety-eight clinically asymptomatic elderly subjects had their plasma ADMA levels screened. Those highest (high ADMA, n = 15) and lowest quartiles distribution (low 13) were eligible receive, randomized order, simvastatin (40 mg/day), L-arginine (3 g/day), or combination both, each for 3 weeks. Endothelium-dependent vasodilation (EDD) was assessed brachial artery ultrasound. Results Simvastatin no effect on EDD with high (6.2 ± 1.2% vs. 6.1 0.9%), whereas plus significantly improved (9.8 1.5% 5.3 0.8%; p Conclusions does not enhance elevated it so patients low ADMA. Combination oral improves but has additional As NO-mediated may play major role therapeutic statins, concentration important factor influences “pleiotropic” simvastatin.