BACKGROUND: Impaired endothelium-dependent vasodilation is an early sign of @entity731 in @entity753 @entity1 . We hypothesized that lipid-lowering therapy can improve endothelial function and that this effect is mainly mediated by increased bioavailability of @entity842 (NO). METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial, we studied 29 @entity1 (age, 50+/-12 years) with @entity1007 (LDL @entity165 > or = 160 mg/dL) randomly assigned to receive either @entity5470 (40 mg twice daily; 17 @entity1 ) or placebo (12 @entity1 ). Forearm blood flow was measured by plethysmography before and after 24 weeks of treatment. Endothelium-dependent vasodilation was assessed by intra-arterial infusion of @entity934 ( @entity1617 ; 3, 12, 24, and 48 microg/min) and basal NO synthesis rate by intra-arterial infusion of @entity7293 ( @entity7293 ; 1, 2, and 4 micromol/min). Simultaneous intra-arterial infusion of @entity7293 (4 micromol/min) and @entity1617 (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 ( @entity1617 24 microg/min: 240+/-34% before versus 347+/-50% after therapy; P< or =0.01) and placebo (changes between after and before therapy with @entity1617 24 microg/min: 108+/-39% for @entity5470 versus -26+/-32% for placebo; P< or =0.05). This improvement in endothelium-dependent vasodilation could be blocked by simultaneous administration of @entity7293 ( @entity1617 24 microg/min plus @entity7293 4 micromol/min: 170+/-69% before versus 219+/-47% after treatment; P=NS). CONCLUSIONS: Lipid-lowering therapy with @entity5470 can improve disturbed endothelial function in @entity753 @entity1 compared with placebo. This improvement is mediated by increased bioavailability of NO.

Increased bioavailability of @entity842 after lipid-lowering therapy in XXXX @entity1 : a randomized, placebo-controlled, double-blind study.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity753 :: ('OMIM:143890', 'Disease') :: ['hypercholesterolemic'] @entity1007 :: ('MESH:D006937', 'Disease') :: ['hypercholesterolemia'] @entity5470 :: ('MESH:C065180', 'Chemical') :: ['fluvastatin'] @entity1617 :: ('CHEBI:22614', 'Chemical') :: ['ACh'] @entity7293 :: ('CHEBI:28229', 'Chemical') :: ['L-NMMA', 'NG-monomethyl-L-arginine'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerosis'] @entity165 :: ('MESH:D002784', 'Chemical') :: ['cholesterol'] @entity934 :: ('MESH:D000109', 'Chemical') :: ['acetylcholine']
@entity753 :: (OMIM:143890,Disease) :: ['hypercholesterolemic']
