Effects of a stabilized endothelium-derived relaxing factor on the coronary vasculature in awake dogs.

The effects of a partially purified endothelium-derived relaxing factor (EDRF) stabilized by acidification from cultured bovine aortic endothelial cells stimulated with the calcium ionophore A23187 on coronary and peripheral vasculature were examined in five awake dogs. The dogs were chronically instrumented with miniature arterial dimension crystals and Doppler flow probes. Intracoronary or intra-arterial infusions of this EDRF induced a rapid (less than 15 s) significant increase in the proximal vessel diameter (P less than 0.02). The duration of proximal dilation response to this EDRF persisted up to 6 min, whereas the smaller changes in distal flow were more transient (less than 1 min). Similar but more pronounced changes in the proximal arterial dilation and distal flow occurred with infusion of nitroglycerin (0.4 mg). No vasoactive changes were observed during infusions of the control vehicle. The vasodilatory effects to this EDRF occurred in the absence of changes in aortic and left ventricular pressure, rate of pressure development (dP/dt), and heart rate. These data demonstrate that infusion of this partially purified relaxing factor from cultured endothelial cells causes vasodilation in vivo with a vasoactive profile similar to nitroglycerin. The biological effects of this EDRF persist significantly longer than the extreme lability of EDRF at neutral pH (approximately 6 s), consistent with its in vitro effects. Despite the demonstration of rapid inactivation of EDRF in vitro by hemoglobin, high oxygen tension, and plasma, the study shows that this EDRF can have significant in vivo vasoactive effects.