Direct in vivo effects of nitric oxide on the coronary circulation

To determine the direct in vivo effects of nitric oxide (NO) on the coronary 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, changes in coronary artery size with quantitative angiography, and transmural myocardial perfusion with radioactive microspheres. Boluses of NO (1-8 μmol) caused a stepwise increase in CBFV (3.1 ± 0.3 × basal CBFV at 8 μmol) similar to that caused by adenosine (2.6 ± 0.3 × basal CBFV, maximal dose). Continuous subselective infusions (0.1, 1.0, and 4.0 μmol/min) caused dose-dependent increases in CBFV (2.2 ± 0.3 × basal CBFV at 4.0 μmol/min) and in epicardial artery diameter (+15 ± 6% diam). Left main infusions (8 μmol/min) caused a stepwise increase in CBFV and in the endocardial-to-epicardial flow ratio without affecting systemic hemodynamics. Brief infusion of NO (2 min) did not 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 elimination, providing direct evidence that NO is a potent in vivo coronary vasodilator. Moreover, the enhanced subendocardial vasodilator response to direct NO infusion suggests increased regional sensitivity to NO.