4.8 Article

Effects of Neuronal Nitric Oxide Synthase on Human Coronary Artery Diameter and Blood Flow In Vivo

期刊

CIRCULATION
卷 119, 期 20, 页码 2656-2662

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.108.822205

关键词

blood flow; microcirculation; nitric oxide; vasculature; vasodilation

资金

  1. British Heart Foundation [PG/05/138/20014, CVH/99001]
  2. Department of Health via the National Institute for Health Research Comprehensive Biomedical Research Centre
  3. Guy's and St Thomas' National Health Service Foundation Trust
  4. National Health Service Foundation Trust
  5. European Union FP6 [LSHM-CT-2005-018833]
  6. EUGeneHeart
  7. British Heart Foundation [FS/09/062/27958] Funding Source: researchfish

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Background-Nitric oxide (NO)-mediated local regulation of vascular tone is considered to involve endothelial NO synthase ( eNOS). However, we recently reported that human forearm basal microvascular tone in vivo is tonically regulated by neuronal NO synthase ( nNOS), in contrast to an acetylcholine-stimulated reduction in tone, which is eNOS dependent. Here, we investigated the in vivo effects of an nNOS-selective inhibitor, S-methyl-L-thiocitrulline (SMTC), on the human coronary circulation and on flow-mediated dilatation in the forearm. Methods and Results-In patients with angiographically normal coronary arteries, intracoronary infusion of SMTC (0.625 mu mol/min) reduced basal coronary blood flow by 34.1 +/- 5.2% (n=10; P<0.01) and epicardial coronary diameter by 3.6 +/- 1.2% (P=0.02) but had no effect on increases in flow evoked by intracoronary substance P (20 pmol/min). The nonselective NOS inhibitor N-G-monomethyl-L-arginine (25 mu mol/min) also reduced basal coronary flow (by 22.3 +/- 5.3%; n=8; P<0.01) but, in contrast to SMTC, inhibited substance P-induced increases in flow (P<0.01). In healthy volunteers, local infusion of SMTC (0.2 mu mol/min) reduced radial artery blood flow by 36.0 +/- 6.4% (n=10; P=0.03) but did not affect flow-mediated dilatation (P=0.55). In contrast, N-G-monomethyl-L-arginine (2 mu mol/min) infusion reduced radial blood flow to a similar degree (by 39.7 +/- 11.8%; P=0.02) but also inhibited flow-mediated dilatation by approximate to 80% (P<0.01). Conclusions-These data indicate that local nNOS-derived NO regulates basal blood flow in the human coronary vascular bed, whereas substance P-stimulated vasodilatation is eNOS mediated. Thus, nNOS and eNOS have distinct local roles in the physiological regulation of human coronary vascular tone in vivo. (Circulation. 2009; 119: 2656-2662.)

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