Effect of pravastatin on responsiveness to N-monomethyl-L-arginine in patients with hypercholesterolaemia.
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.
Bayerle-Eder
Michaela
M
Department of Clinical Pharmacology, Allgemeines Krankenhaus Wien, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Fuchsjäger-Mayrl
Gabriele
G
Sieder
Anna
A
Polska
Elzbieta
E
Roden
Michael
M
Stulnig
Thomas
T
Bischof
Martin G
MG
Waldhäusl
Werner
W
Schmetterer
Leopold
L
Wolzt
Michael
M
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*
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D014280:Triglycerides; D019323:omega-N-Methylarginine; D002784:Cholesterol; D017035:Pravastatin