Augmented basal nitric oxide production contributes to maintenance of coronary blood flow in dogs with pacing-induced heart failure.

It remains controversial whether basal nitric oxide (NO) production in coronary resistance vessels in heart failure is enhanced or not. A transonic Doppler flow probe was placed around the left anterior descending coronary artery, and complete atrioventricular block was produced in fifteen dogs. The coronary pressure-flow relationships during long diastole were analyzed without and with pacing-induced heart failure. Three weeks after pacing at 240/ min, plasma norepinephrine and renin activity significantly rose. Right atrial pressure and left ventricular end-diastolic pressure increased, and cardiac output and coronary perfusion pressure decreased; however, mean coronary blood flow did not change after pacing (55 ± 5 to 52 ± 5 ml/min/100 g, mean ± SEM). The slope of the diastolic coronary pressure-flow relationship became steeper (1.22 ± 0.13 to 1.62 ± 0.09 ml/min/100 g/mmHg, p < 0.05) with a slight increase in the measured zero-flow pressure (29.5 ± 1.1 to 32.8 ± 1.5 mmHg, p < 0.05) after pacing. After pretreatment with indomethacin, administration of N G -nitro-L-arginine methyl ester caused an equal increase in the zero-flow pressure before (31.4 ± 1.7 to 39.2 ± 2.2 mmHg, p < 0.05) and after heart failure (33.9 ± 2.5 to 41.6 ± 2.2 mmHg, p < 0.05), and more decline of the slope of the coronary pressure-flow relationship in heart failure (1.86 ± 0.22 to 1.20 ± 0.05 ml/min/100 g/mmHg,p < 0.05) than before heart failure (1.11 ± 0.12 to 1.05 ± 0.11 ml/min/100 g/mmHg, N.S.). This indicates that in failing hearts the vasodilatory action of NO in small vessels predominates despite the presence of several vasoconstricting factors. These results suggest that coronary blood flow is maintained despite detrimental hemodynamic and activated neurohumoral factors in the initial stage of heart failure, and that increased basal NO production plays a central role in the maintenance of basal coronary blood flow.