当前位置： SCI文献检索 > JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY期刊下所有文献 > Once daily therapy with isosorbide-5-mononitrate causes endothelial dysfunction in humans: evidence of a free-radical-mediated mechanism.

Once daily therapy with isosorbide-5-mononitrate causes endothelial dysfunction in humans: evidence of a free-radical-mediated mechanism.

Abstract：

OBJECTIVES:The aim of the study was to determine if isosorbide-5-mononitrate (IS-5-MN) 120 mg, taken once daily for 7 days, is associated with evidence of endothelial dysfunction and whether this effect is determined by increased free radical production. BACKGROUND:Tolerance to nitroglycerin is associated with increased free radical production and abnormal endothelial function. To date, no data is available concerning the effect of IS-5-MN, administered in clinically employed dosages, on endothelial function in humans. METHODS:A total of 19 healthy volunteers were randomized in a double-blind fashion to therapy with IS-5-MN (120 mg once daily) or placebo. After 7 days of treatment, forearm blood flow responses to acetylcholine (Ach; 7.5, 15, and 30 microg/min) and N-monomethyl-L-arginine (L-NMMA; 1, 2, and 4 mumol/min) were measured. In a separate study, after 7 days of therapy with IS-5-MN 120 mg once daily, the responses to Ach were assessed during intra-arterial coinfusion of vitamin C (24 mg/min) or saline. RESULTS:As compared with placebo, IS-5-MN caused significant blunting of the responses to both Ach (peak responses: placebo 127 +/- 31%; IS-5-MN 52 +/- 24%) and L-NMMA (peak responses: placebo 41 +/- 5%; IS-5-MN 22 +/- 8%). Vitamin C completely restored the forearm blood flow responses to Ach (peak responses: vitamin C 180 +/- 33%; saline 107 +/- 17%). CONCLUSIONS:We document for the first time that IS-5-MN impairs endothelial function in humans in vivo. Suggesting a role of oxygen free radicals, nitrate-induced abnormalities in endothelium-dependent vasomotor responses were reversed by the antioxidant vitamin C.

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Thomas GR,DiFabio JM,Gori T,Parker JD

doi

10.1016/j.jacc.2006.10.074

subject

Has Abstract

pub_date

2007-03-27 00:00:00

pages

1289-95

issue

12

eissn

0735-1097

issn

1558-3597

pii

S0735-1097(07)00132-5

journal_volume

49

pub_type

杂志文章,随机对照试验

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