Perfused rabbit heart: endothelium-derived relaxing factor in coronary arteries

The study was performed to demonstrate the presence of the endothelium-derived relaxing factor (EDRF), previously found to be active in isolated artery preparations in vitro, in the coronary arteries of rabbits remaining in contact with the beating perfused heart. This was accomplished by following the response of the preconstricted obtuse marginal coronary artery to topically administered acetylcholine (ACH). Both intact arteries and arteries in which the endothelium had been removed were studied. Preconstriction of the obtuse marginal coronary artery was accomplished by topical application (spray) of histamine (10 microM), in 2 ml Krebs-Henseleit (KH) solution. This resulted in a decrease in internal diameter of the coronary artery, a decline in coronary flow, and an increase in total coronary vascular resistance. The principal difference between intact coronary arteries and those in which the endothelium had been removed was in the response to ACH. In arteries with intact endothelium preconstricted with histamine, topical administration (spray) of ACH (0.6 mM in 2 ml KH solution) caused, as compared with histamine, an increase in coronary flow, a significant decrease in total coronary vascular resistance, and a rise in internal vascular diameter. Arteries in which the vascular endothelium had been removed, as compared to those pretreated with histamine, responded to topical administration of ACH (0.6 mM in 2 ml KH solution) with a decrease in coronary flow, coronary vascular resistance, and internal vascular diameter. No change in the dose-response curve to histamine between the two preparations was noted. The results demonstrate that coronary vascular endothelium exerts a protective effect in coronary arteries remaining in contact with the perfused beating heart.