Abstract

Vasodilation mediated by endothelium-derived relaxing factor (EDRF) has been demonstrated in large conduit arteries in vitro. In the present study we investigated whether the EDRF mechanism is also present in resistance arteries of a peripheral vascular bed, namely the hindlimb of the rabbit. The right femoral artery of anesthetized rabbits was cannulated and blood was supplied through a shunt from the carotid artery. Femoral arterial blood flow and pressure were measured in the shunt. Systemic pressure was measured in the abdominal aorta. The hemodynamic effects of endothelium-dependent and -independent vasodilators (infused into the shunt) were measured before and after treatment of the vascular bed with gossypol or p-bromophenacyl bromide (p-BPB). Gossypol, a polyphenolic antioxidant, is a selective and irreversible inhibitor of the EDRF-mediated vasodilation in isolated arteries; p-BPB is an alkylating agent and also produces irreversible inhibition of endothelium-mediated relaxations in vitro. During inhibitor treatment the hindlimb was temporarily isolated from the blood circulation and perfused with a cell-free medium; the venous effluent was drained off so that only minimal amounts of inhibitor reached the systemic circulation. The endothelium-dependent vasodilators acetylcholine (ACh) and substance P, and the endothelium-independent vasodilators prostaglandin E1 (PGE1) and glyceryl trinitrate (GTN) induced concentration-dependent increases in femoral arterial flow (and decreases in vascular resistance). Gossypol treatment had no direct effect on systemic blood pressure or femoral arterial flow. However, after gossypol, the effects of ACh and substance P on vascular resistance were almost abolished, but there was no significant effect on the responses to PGE1 and GTN.(ABSTRACT TRUNCATED AT 250 WORDS)