title: Simvastatin, capillary permeability, and acetylcholine-mediated vasomotion in atherosclerotic, hypercholesterolemic men.
abstract: OBJECTIVE
  The aim of this study was to test the effect of high-dose simvastatin therapy on vascular permeability, a key variable in the atherogenic process, and endothelial-mediated vasodilator responses in patients with hypercholesterolemic atherosclerosis.
  
  
  METHODS
  The transcapillary albumin escape rate (TERalb, the 1-hour decline rate of intravenous 125I-albumin, a measure of macromolecular permeability of capillary endothelium) and forearm vasodilatation (venous plethysmography) to intraarterial acetylcholine and sodium nitroprusside (7.5, 15, 30 microg/min and 0.8, 1.6, and 3.2 microg/min respectively, 5 minutes at each rate) to account for endothelium-dependent and independent mechanisms, were measured at baseline and after 1-month simvastatin (40 mg once daily) in 16 hypercholesterolemic (low-density lipoprotein cholesterol >130 mg/dL), atherosclerotic men. Thirteen healthy, untreated subjects were the controls.
  
  
  RESULTS
  Baseline TERalb was higher and responsiveness to both acetylcholine and sodium nitroprusside was depressed in patients compared with controls. One-month high-dose simvastatin reduced low-density lipoprotein cholesterol by 39%, normalized TERalb, and improved local vasomotor responses to acetylcholine, without modifying those to sodium nitroprusside. Changes in TERalb and acetylcholine-mediated vasodilatation were dissociated and unrelated to lipid modifications.
  
  
  CONCLUSIONS
  Low-density lipoprotein cholesterol reduction through 1 month of high-dose simvastatin normalized the exaggerated transvascular albumin leakage of patients with hypercholesterolemic atherosclerosis, perhaps by restoring an exaggerated endothelial permeability, apparently through mechanisms independent of circulating lipids. Improvements in acetylcholine-mediated vasomotion were also evident, but were dissociated from TERalb, demonstrating a heterogeneous behavior of the 2 indices of endothelial function in response to high-dose statin treatment.
authors.affiliation: Dipartimento Cardio-Toracico and Malattie Metaboliche, Universita' di Pisa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Dell'Omo
authors.forename: S
authors.initials: S
authors.lastname: Bandinelli
authors.forename: G
authors.initials: G
authors.lastname: Penno
authors.forename: R
authors.initials: R
authors.lastname: Pedrinelli
authors.forename: M
authors.initials: M
authors.lastname: Mariani
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001161:Arteriosclerosis / Q000378:metabolism / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D016022:Case-Control Studies; D008078:Cholesterol, LDL / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006937:Hypercholesterolemia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000378:metabolism; D019821:Simvastatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019821:Simvastatin; D000109:Acetylcholine