CONTRIBUTION OF NITRIC-OXIDE TO CORONARY VASODILATION DURING HYPERCAPNIC ACIDOSIS

The present study was performed to evaluate the role of nitric oxide ( NO) in coronary vasodilation during hypercapnic acidosis (HC). The lef t anterior descending coronary arteries of 17 anesthetized, open-chest dogs were perfused with normal arterial blood or with arterial blood equilibrated in an extracorporeal circuit with 90% O-2-10% CO2 [arteri al carbon dioxide tension (Pace,) 72 +/- 3 mmHg, arterial pH 7.16 +/- 0.02]. Coronary perfusion pressure (CPP) was initially set at 100 mmHg . Coronary blood flow (CBF) was measured with a Doppler transducer. St udies were conducted under constant-pressure (variable CBF; n = 13) an d constant-flow (variable CPP) conditions (n = 4). Steady-state change s in CBF (or CPP) during HC and during intracoronary infusions of acet ylcholine (ACh, 20 mu g/min), an endothelium-dependent vasodilator, an d sodium nitroprusside (SNP, 80 mu g/min), an endothelium-independent vasodilator, were compared before and after intracoronary infusion of a NO synthase inhibitor, either NG-nitro-L-arginine methyl ester (L-NA ME, 4.5 mg) or NG-monomethyl-L-arginine (L-NMMA, 30 mg). Under constan t pressure, L-NAME blunted increases in CBF by HC (274 +/- 32 vs. 113 +/- 24%) and ACh (400 +/- 43 vs. 68 +/- 17%), whereas increases in CBF by SNP were not significantly affected (207 +/- 34 vs. 186 +/- 18%). Results with L-NMMA were similar. Under constant flow, L-NAME attenuat ed decreases in CPP by HC and ACh, whereas it had no significant effec t on decreases in CPP by SNP. In conclusion, HC elicits release of NO from coronary vascular endothelium via a direct effect rather than sec ondary to an increased flow rate. The present findings suggest that NO makes an important contribution to coronary vasodilation during HC.