Alterations of endothelium-dependent and -independent regulation of coronary blood flow during heart failure.

Conflicting data concerning the changes in basal coronary blood flow and nitric oxide (NO)-releasing capacity in chronic heart failure may be due to different phases or duration of heart failure. To investigate endothelium-dependent and -independent regulation of coronary blood flow in different phases of heart failure, coronary pressure-flow relationships during long diastole were obtained before and after rapid pacing of 3 and 5 wk at 240 beats/min in 12 or 6 dogs. Neither basal coronary blood flow nor the slope of coronary pressure-flow relationships changed; however, zero-flow pressure increased slightly after rapid pacing. Intracoronary injection of N(G)-nitro-L-arginine methyl ester decreased coronary blood flow at a perfusion pressure of 50 mmHg by approximately 20% at baseline, 55% after 3 wk of rapid pacing, and 20% after 5 wk of rapid pacing. Acetylcholine-induced increase in coronary blood flow was maintained for 3 wk but was finally attenuated after 5 wk of rapid pacing. In contrast, the coronary blood flow response to adenosine gradually decreased with time. These results suggest that basal coronary blood flow is maintained until the late stage of heart failure, presumably by an increases in NO production during the early stage and then by other vasodilatory substances during the late stage, and that endothelium-dependent vasodilation via exogenously administered acetylcholine in resistance vessels is not necessarily impaired in the early stage despite the gradual reduction of endothelium-independent vasodilation via adenosine in chronic heart failure.