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

John, Stefan and Schlaich, Markus and Langenfeld, Mathias and Weihprecht, Horst and Schmitz, Gerd and Weidinger, Gottfried and Schmieder, Roland E. (1998) Increased bioavailability of nitric oxide after lipid-lowering therapy in hypercholesterolemic patients - A randomized, placebo-controlled, double-blind study. CIRCULATION, 98 (3). pp. 211-216. ISSN 0009-7322,

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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 greater than or equal to 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 mu g/min) and basal NO synthesis rare by intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA; 1, 2, and 4 mu mol/min). Simultaneous intra-arterial infusion of L-NMMA (4 mu mol/min) and ACh (12, 24, and 48 mu g/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 mu g/min: 240+/-34% before versus 347+/-50% after therapy; P less than or equal to 0.01) and placebo (changes between after and before therapy with ACh 24 mu g/min: 108+/-39% for fluvastatin versus -26+/-32% for placebo; P less than or equal to 0.05). This improvement in endothelium-dependent vasodilation could be blocked by simultaneous administration of L-NMMA (ACh 24 mu g/min plus L-NMMA 4 mu mol/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.

Item Type: Article
Uncontrolled Keywords: ENDOTHELIUM-DEPENDENT VASODILATION; SUPEROXIDE ANION PRODUCTION; FOREARM RESISTANCE VESSELS; SERUM-CHOLESTEROL; BLOOD-FLOW; CORONARY; ATHEROSCLEROSIS; DISEASE; RISK; VASOMOTION; atherosclerosis; endothelium; blood flow; hypercholesterolemia; nitric oxide; vasodilation
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin
Depositing User: Dr. Gernot Deinzer
Date Deposited: 02 May 2023 13:33
Last Modified: 02 May 2023 13:33
URI: https://pred.uni-regensburg.de/id/eprint/49664

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