Importance of nitric oxide in the coronary artery at rest and during pacing in humans

Department of Medicine, Tokyo Dental College, Japan.

OBJECTIVES: The purpose of this study was to investigate the role of endothelium-dependent vascular regulation in the human coronary circulation during rest and hyperemic states. BACKGROUND: Evidence of the role of nitric oxide (NO) during metabolic demand is not consistent in animal and human coronary circulation. METHODS: NG-Monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthesis, was infused into the left anterior descending coronary artery at rest and during rapid atrial pacing in 18 subjects--9 with normal coronary arteries (control) and 9 with atherosclerotic coronary arteries. The diameter of the epicardial coronary artery was measured by quantitative coronary angiography. Vasodilation of the coronary microcirculation was assessed using an intracoronary Doppler FloWire. RESULTS: Infusion of 25 mumol/min of L-NMMA reduced the diameter of the proximal and distal epicardial coronary artery segments by 8 +/- 2% (mean +/- SE) and 11 +/- 2%, respectively (p < 0.05) in the control subjects. The coronary blood flow (CBF) decreased by 33 +/- 13% during L-NMMA infusion. L-NMMA caused similar changes in the diameter of the distal epicardial segment and the CBF in patients with coronary artery disease. The proximal vessel diameter did not change significantly during infusion of L-NMMA. During pacing, infusion of L-NMMA caused the same changes in vessel diameter as before pacing in both groups, but did not affect CBF. CONCLUSIONS: Our findings indicate that NO synthesis maintains basal vasomotor tone in both conduit and resistance vessels in the normal human coronary circulation. Although NO release was impaired in the large epicardial coronary arteries in patients with atherosclerosis, NO still regulated vascular tone in the small epicardial coronary arteries and arterioles. Our results suggest that vasodilation in arterioles during increased myocardial oxygen demand is mediated by metabolic or myogenic mechanisms, or both, rather than by endothelium-dependent production of NO.

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