title: Simvastatin reduces endothelial NOS: caveolin-1 ratio but not the phosphorylation status of eNOS in vivo.
abstract: In vivo evidence for the pleiotropic effects of simvastatin on the nitric oxide synthase system is limited.
  
  
  OBJECTIVE
  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 (r(2)= 0.5, p=0.01).
  
  
  CONCLUSIONS
  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.
authors: Department of Medicine, University of Melbourne, Austin Health, Australia.
authors: Rajneet
authors: R
authors: Arora
authors: David L
authors: DL
authors: Hare
authors: Anthony
authors: A
authors: Zulli
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D011817:Rabbits; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D051242:Caveolin 1; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D019821:Simvastatin; D052250:Nitric Oxide Synthase Type III