Quantitative aspects of the inhibition by NG-monomethyl-L-arginine of responses to endothelium-dependent vasodilators in human forearm vasculature

被引:22
作者
Dawes, M
Chowienczyk, PJ
Ritter, JM
机构
[1] St Thomas Hosp, Dept Clin Pharmacol, London SE1 7EH, England
[2] Univ London Kings Coll, Ctr Cardiovasc Biol & Med, London SE1 7EH, England
关键词
N-G-monomethyl-L-arginineacetylcholine; human forearm vasculature; endothelium; nitric oxide; albuterol;
D O I
10.1038/sj.bjp.0704338
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1. N-G-monomethyl-L-arginine (L-NMMA) constricts human forearm resistance vasculature and selectively attenuates vasodilator responses to endothelium-dependent vasodilators. Incomplete inhibition of such responses could be due to an inadequate dose of L-NMMA or to NO-independent vasodilator mechanisms. 2 This study sought to determine doses Of L-NMMA that are maximally effective in reducing basal and stimulated forearm blood flow. Drugs were infused via the brachial artery in 32 healthy men. Acetylcholine (11-330 nmol min(-1)) was compared with albuterol (0.33-10 nmol min(-1)), and nitroprusside (1.7-20 nmol min(-1)). 3 The effect of L-NMMA on basal flow approached maximum (53 +/- 2% reduction) at a dose of 16 mu mol min(-1). L-NMMA (16 mu mol min(-1)) did not significantly influence responses to nitroprusside, but antagonized acetylcholine and albuterol (each P < 0.001, by repeated measures analysis of variance). 4 Inhibition of acetylcholine by L-NMMA (16 mu mol min(-1)) was strongly influenced by acetylcholine dose (73 +/- 7% inhibition at 11 nmol min(-1), P < 0.01; 4 +/- 11% inhibition at 330 nmol min(-1) P = NS, Student's paired t-test). Significant inhibition of albuterol was observed at all doses. 5 A higher dose of L-NMMA (64 mu mol min(-1)) did not significantly inhibit the response to acetylcholine (330 nmol min(-1)). Responses to this dose of acetylcholine were unaffected by a cyclooxygenase (COX) inhibitor (indometacin) alone but combined COX and NO inhibition attenuated acetylcholine responses by 42 +/- 19%, implying that there is a compensatory increase in the contribution of prostaglandins or NO to acetylcholine-induced dilatation when one or other pathway is inhibited.
引用
收藏
页码:939 / 944
页数:6
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