title: Effect of pravastatin on responsiveness to N-monomethyl-L-arginine in patients with hypercholesterolaemia.
abstract: Improvement of endothelial function in hypercholesterolaemia is attributed to lipid lowering and to pleiotropic effects of statin therapy. We investigated whether responsiveness to inhibition of constitutive NO formation with N-monomethyl-L-arginine (L-NMMA) is improved after 7 and 28 days of pravastatin. Twelve female and four male subjects with mild or moderate primary hypercholesterolaemia were randomized to pravastatin (20 mg per oral (p.o.) n=8) or placebo (n=8) in a double blind parallel group design. Vascular responsiveness was studied by intravenous bolus infusions of L-NMMA (cumulative doses of 3 and 6 mg/kg). Mean arterial blood pressure (MAP) and pulse rate (PR) were measured noninvasively, pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation amplitudes (FPA) and renal plasma flow (RPF) was measured by the PAH clearance method. Pravastatin lowered plasma cholesterol levels by 16 and 24% after 7 and 28 days of treatment, respectively (P<0.01). L-NMMA caused comparable changes in MAP, PR and RPF between groups. L-NMMA reduced FPA to a similar extent in both groups before and after 7 days of treatment, but the response to L-NMMA was significantly enhanced after 28 days of pravastatin (21%; P<0.001 vs baseline) and greater than after placebo (15%; P<0.01 vs pravastatin). Pravastatin enhances responsiveness to L-NMMA in the ocular microvasculature. Improved responsiveness is associated with changes in total cholesterol levels.
authors.affiliation: Department of Clinical Pharmacology, Allgemeines Krankenhaus Wien, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Bayerle-Eder
authors.forename: Gabriele
authors.initials: G
authors.lastname: Fuchsjäger-Mayrl
authors.forename: Anna
authors.initials: A
authors.lastname: Sieder
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Polska
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.forename: Thomas
authors.initials: T
authors.lastname: Stulnig
authors.forename: Martin G
authors.initials: MG
authors.lastname: Bischof
authors.forename: Werner
authors.initials: W
authors.lastname: Waldhäusl
authors.forename: Leopold
authors.initials: L
authors.lastname: Schmetterer
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
mesh_terms: D001315:Australia; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D019323:omega-N-Methylarginine / Q000187:drug effects*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D014280:Triglycerides; D019323:omega-N-Methylarginine; D002784:Cholesterol; D017035:Pravastatin