DIRECT IN-VIVO EFFECTS OF NITRIC-OXIDE ON THE CORONARY CIRCULATION

To determine the direct in vivo effects of nitric oxide (NO) on the co ronary circulation, we infused NO-saturated saline (1.0 +/- 0.1 mmol/l ) into the coronary arteries of anesthetized dogs and measured changes in coronary blood flow velocity (CBFV) with a Doppler catheter, chang es in coronary artery size with quantitative angiography, and transmur al myocardial perfusion with radioactive microspheres. Boluses of NO ( 1-8 mu mol) caused a stepwise increase in CBFV (3.1 +/- 0.3 x basal CB FV at 8 mu mol) similar to that caused by adenosine (2.6 +/- 0.3 x bas al CBFV, maximal dose). Continuous subselective infusions (0.1, 1.0, a nd 4.0 mu mol/min) caused dose-dependent increases in CBFV (2.2 +/- 0. 3 x basal CBFV at 4.0 mu mol/min) and in epicardial artery diameter (15 +/- 6% diam). Left main infusions (8 mu mol/min) caused a stepwise increase in CBFV and in the endocardial-to-epicardial flow ratio witho ut affecting systemic hemodynamics. Brief infusion of NO (2 min) did n ot significantly reduce acetylcholine-mediated endothelial NO release. Therefore, despite rapid metabolism, direct intraarterial infusion of NO can be given at a rate sufficient to overwhelm metabolic eliminati on, providing direct evidence that NO is a potent in vivo coronary vas odilator. Moreover, the enhanced subendocardial vasodilator response t o direct NO infusion suggests increased regional sensitivity to NO.