Simvastatin reduces endothelial NOS: Caveolin-1 ratio but not the phosphorylation status of eNOS in vivo

In vivo evidence for the pleiotropic effects of simvastatin on the nitric oxide synthase system is limited. aims: to determine if simvastatin can affect the endothelial nitric oxide synthase cascade. methods: new zealand white rabbits (n=15) were divided: group 1 (control) was fed a normal rabbit diet; group 2 (mc) received a normal rabbit diet with 1% methionine (m) plus 0.5% cholesterol (c) and 5% peanut oil (atherogenic diet); group 3 received the same diet as the mc group plus 5 mg/kg/ day simvastatin (s) orally (mcs). after 4 weeks,the abdominal aorta was collected and analyzed. results: total cholesterol (tc) and total homocysteine (thcy) were not significantly different between mcs and mc. endothelial function was only reduced in mc (p<0.05). although enos significantly increased in mc and mcs (p<0.01),simvastatin treatment significantly reduced endothelial caveolin-1 by 35% (p= 0.038),causing a 2.5-fold (p=0.026) increase in the enos: caveolin-1 ratio. the phosphorylation of enos at the threonine 495 site or serine 1177 site was not affected by diet or treatment; however,a positive correlation between the two phosphorylation sites was observed (r2 = 0.5,p= 0.01). conclusion: in vivo pleiotropic effects of statin therapy include decreasing endothelial caveolin-1. other therapies designed to affect enos phosphorylation in vivo might be useful in further preventing cvd.