Formation and functional importance of endothelium-derived relaxing factor (EDRF) and prostaglandins in the microcirculation.

Vasodilation mediated by endothelium-derived relaxing factor (EDRF) has been demonstrated in large conduit arteries in vitro. Experiments were undertaken to investigate whether EDRF can also be produced in the microcirculation and thus could participate in the regulation of peripheral resistance. In a first series of experiments we studied a peripheral vascular bed, the hindlimb of the rabbit. The right femoral artery of anaesthetized rabbits was cannulated and blood was supplied through a shunt from the carotid artery. Blood flow through the hindlimb was measured in the shunt. Systemic pressure was measured in the abdominal aorta. Vascular resistance in the hindlimb was calculated from the two parameters. The haemodynamic effects of endothelium-dependent and -independent vasodilators (infused into the shunt) were measured before and after selective treatment of the vascular bed with gossypol, an irreversible inhibitor of the production or release of EDRF. The endothelium-dependent vasodilators acetylcholine and substance P, and the endothelium-independent vasodilators prostaglandin E1 and glyceryl trinitrate induced dose-dependent decreases in vascular resistance. Gossypol almost abolished the effects of acetylcholine and substance P on vascular resistance, but had no significant effect on the responses to prostaglandin E1 and glyceryl trinitrate. Also the decrease in peripheral resistance produced by hydralazine was not affected by gossypol although in the same rabbits the response to acetylcholine was inhibited by more than 70%. In bioassay experiments the production of EDRF was measured from cultured human microvascular (omentum) and macrovascular (umbilical vein) endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)