(Circulation. 1995;91:1807-1813.)
© 1995 American Heart Association, Inc.
Articles |
Role of Nitric Oxide in the Coronary Microvascular Responses to Adenosine and Increased Metabolic Demand
From the Department of Medical Physiology, Microcirculation Research Institute, Texas A&M University Health Science Center, College Station.
Correspondence to Dr William M. Chilian, Department of Medical Physiology, Microcirculation Research Institute, Texas A&M University Health Science Center, College Station, TX 77843-1114.
Background The purpose of this study was to test the hypothesis that endothelium-derived nitric oxide (NO) participates in coronary microvascular responses to adenosine and pacing-induced increases in metabolic demand by maintaining an optimal distribution of coronary resistance.
Methods and Results Coronary microvascular diameters were measured by stroboscopic epi-illumination and intravital microscopy in open-chest dogs (n=20). Epicardial coronary blood velocity (CBV) was measured by Doppler flowmetry. Responses to adenosine (1 and 10 µg · kg-1 · min-1 IC) and left atrial pacing (180 beats per minute) were recorded before and after inhibition of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME, 30 µg · kg-1 · min-1 IC). At baseline, adenosine dilated arterioles (<100 µm) (11±4% and 25±3% diameter changes, P<.05) more than small arteries (>100 µm) (-4±6% and 7±3%, P<.05 for the higher dose) and increased CBV (43±31% and 118±25%, P<.05). Left atrial pacing dilated arterioles (12±2%, P<.05) and small arteries (8±3%, P<.05) and also increased CBV (68±9%, P<.05). L-NAME abolished CBV increases caused by acetylcholine (10 and 100 ng · kg-1 · min-1 IC; 53±33% and 168±82% versus -12±15% and -1±14%, P<.05) but not papaverine. Small arteries were constricted by L-NAME (-8±2%, P<.05), arterioles were dilated (10±4%, P<.05), and CBV was unchanged. After L-NAME, adenosine failed to dilate arterioles further (3±3% and 2±2%; P<.05 versus prior responses), and CBV changes were attenuated (14±16% and 8±13%; P<.05 versus prior responses). Pacing also failed to dilate arterioles (-4±2%, P<.05 versus prior response), resulting in an attenuated CBV change (34±13%, P<.05 versus prior response). The possibility that adenosine stimulates NO release in canine coronary arterioles was investigated in isolated arterioles (diameters, 81±4 µm; n=8). Adenosine caused dose-dependent dilation to maximal diameter, which was unaffected by inhibition of NO synthesis by L-NAME.
Conclusions Inhibition of NO synthesis attenuates coronary dilation during adenosine infusions and during pacing-induced increases in metabolic demand. Inhibition of NO synthesis may shift the major site of coronary resistance into small arteries through autoregulatory adjustments in arterioles. These data therefore suggest that NO, by dilating predominantly small coronary arteries, promotes metabolic coronary dilation by preserving the tone and vasodilator reserve of arterioles.
Key Words: metabolism • vasodilation • blood flow • adenosine • endothelium-derived factors • microcirculation
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