Atorvastatin increases ecNOS levels in human platelets of hyperlipidemic subjects

Background. The purpose of this study was to probe the pleiotrophic effects of Atorvastatin on intraplatelet-nitric oxide metabolism. Methods and Resu lts. Hyperlipidemic subjects (n = 19) were treated for 1 month (following a 3-week washout) with either Atorvastatin or placebo in a double-blinded ra ndomized (n = 2, crossover), placebo-controlled study. Changes in the level s of intraplatelet nitric oxide synthase, nitrotyrosine were correlated wit h cholesterol, LDL-C, HDLC and triglyceride levels. These studies indicate that with atrovastatin ecNOS levels increased on average by similar to 1.7- fold (paired t-test p = 0.009). Interestingly, levels of nitrotyrosylated p latelet proteins, an indication of peroxynitrite damage, decreased as ecNOS levels increased in presence of the drug (paired t-test p = 0.33). Atorvas tatin, at 10 mg per day, lowered cholesterol and LDL-C levels in all patien ts with the average lowering of similar to 21% and similar to 17% respectiv ely. The effect on HDL was not significant whilst triglyceride levels were lowered by an average of similar to 18%. Conclusions. This study adds to th e volume of evidence that statins have beneficial effects other than lipid lowering. Hen, Atorvastatin is shown to significanly elevate intraplatelet ecNOS levels in hyperlipidemic subjects without affecting iNOS expression. The net result of this would be the elevation of NO production which would promote platelet deaggregation and vasodilation.