Document Detail


Effects of neuronal nitric oxide synthase on human coronary artery diameter and blood flow in vivo.
MedLine Citation:
PMID:  19433760     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 micromol/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 micromol/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 micromol/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 micromol/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 approximately 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.
Authors:
Michael Seddon; Narbeh Melikian; Rafal Dworakowski; Husain Shabeeh; Benyu Jiang; Jonathan Byrne; Barbara Casadei; Philip Chowienczyk; Ajay M Shah
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-11
Journal Detail:
Title:  Circulation     Volume:  119     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-27     Completed Date:  2009-06-24     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2656-62     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Citrulline / administration & dosage,  analogs & derivatives,  pharmacology
Coronary Circulation / drug effects,  physiology*
Coronary Vessels / physiology*
Forearm / blood supply
Humans
Male
Nitric Oxide / physiology
Nitric Oxide Synthase Type I / antagonists & inhibitors,  physiology*
Nitric Oxide Synthase Type III / physiology
Regional Blood Flow / drug effects
Substance P / physiology
Thiourea / administration & dosage,  analogs & derivatives,  pharmacology
Vasodilation* / drug effects
Young Adult
Grant Support
ID/Acronym/Agency:
CVH/99001//British Heart Foundation; FS/09/062/27958//British Heart Foundation; PG/05/138/20014//British Heart Foundation; //Department of Health
Chemical
Reg. No./Substance:
156719-41-4/S-methylthiocitrulline; 29VT07BGDA/Citrulline; 31C4KY9ESH/Nitric Oxide; 33507-63-0/Substance P; EC 1.14.13.39/NOS1 protein, human; EC 1.14.13.39/NOS3 protein, human; EC 1.14.13.39/Nitric Oxide Synthase Type I; EC 1.14.13.39/Nitric Oxide Synthase Type III; GYV9AM2QAG/Thiourea

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