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Increased bioavailability of nitric oxide after lipid-lowering therapy in hypercholesterolemic patients: a randomized, placebo-controlled, double-blind study.

Abstract：

BACKGROUND:Impaired endothelium-dependent vasodilation is an early sign of atherosclerosis in hypercholesterolemic patients. We hypothesized that lipid-lowering therapy can improve endothelial function and that this effect is mainly mediated by increased bioavailability of nitric oxide (NO). METHODS AND RESULTS:In a randomized, double-blind, placebo-controlled trial, we studied 29 patients (age, 50+/-12 years) with hypercholesterolemia (LDL cholesterol > or = 160 mg/dL) randomly assigned to receive either fluvastatin (40 mg twice daily; 17 patients) or placebo (12 patients). Forearm blood flow was measured by plethysmography before and after 24 weeks of treatment. Endothelium-dependent vasodilation was assessed by intra-arterial infusion of acetylcholine (ACh; 3, 12, 24, and 48 microg/min) and basal NO synthesis rate by intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA; 1, 2, and 4 micromol/min). Simultaneous intra-arterial infusion of L-NMMA (4 micromol/min) and ACh (12, 24, and 48 microg/min) was used to test whether any increase in endothelium-dependent vasodilation after lipid-lowering therapy could be blocked by this NO synthase inhibitor. Endothelium-dependent vasodilation improved significantly after 24 weeks of lipid-lowering therapy compared with before therapy (ACh 24 microg/min: 240+/-34% before versus 347+/-50% after therapy; P< or =0.01) and placebo (changes between after and before therapy with ACh 24 microg/min: 108+/-39% for fluvastatin versus -26+/-32% for placebo; P< or =0.05). This improvement in endothelium-dependent vasodilation could be blocked by simultaneous administration of L-NMMA (ACh 24 microg/min plus L-NMMA 4 micromol/min: 170+/-69% before versus 219+/-47% after treatment; P=NS). CONCLUSIONS:Lipid-lowering therapy with fluvastatin can improve disturbed endothelial function in hypercholesterolemic patients compared with placebo. This improvement is mediated by increased bioavailability of NO.

journal_name

Circulation

journal_title

Circulation

authors

John S,Schlaich M,Langenfeld M,Weihprecht H,Schmitz G,Weidinger G,Schmieder RE

doi

10.1161/01.cir.98.3.211

subject

Has Abstract

pub_date

1998-07-21 00:00:00

pages

211-6

issue

eissn

0009-7322

issn

1524-4539

journal_volume

pub_type

临床试验,杂志文章,随机对照试验

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Increased bioavailability of nitric oxide after lipid-lowering therapy in hypercholesterolemic patients: a randomized, placebo-controlled, double-blind study.