Inhibition of nitric oxide production aggravates myocardial hypoperfusion during exercise in the presence of a coronary artery stenosis

Abstract

Regulation of coronary vasomotor tone during myocardial hypoperfusion is incompletely understood. The present study was performed to test the hypothesis that endogenous production of nitric oxide contributes to resistance vessel dilation distal to a coronary artery stenosis that results in myocardial ischemia during exercise. Seven dogs instrumented with a Doppler velocity probe, hydraulic occluder, and indwelling microcatheter in the left anterior descending coronary artery (LAD) were studied during treadmill exercise in the presence of a coronary artery stenosis before and after intracoronary infusion of N(G)-nitro-L-arginine (LNNA, 20 mg/kg). This dose of LNNA inhibited the maximal increase in LAD flow produced by intracoronary acetylcholine by 82±5% but did not alter the response to intracoronary nitroprusside. Coronary pressure distal to the stenosis was maintained constant during the control period and after administration of LNNA. LNNA increased aortic and left ventricular systolic and end-diastolic pressures at rest and during exercise. During control in the absence of a stenosis, LNNA had no effect on coronary blood flow. In the presence of a stenosis that decreased distal coronary pressure to 55±2 mm Hg, mean myocardial blood flow measured with microspheres was 1.09±0.13 mL · min-1 · g-1 in the LAD-dependent and 2.57±0.50 mL · min-1 g -1 in the posterior control region, respectively. With no change in distal coronary pressure, LNNA decreased mean myocardial blood flow in the LAD region to 0.68±0.11 mL · min-1 · g-1 (P