Differential effects of leukotrienes C4, D4 and E4 in the canine renal and mesenteric vascular beds.

Although leukotrienes (LTs) have been studied extensively with regard to their influence in the lung and the heart, little is known about the actions of these agents in other important vascular beds. In this study, effects of close-arterial injections of synthetic LTs C4, D4 and E4 were determined in the renal and superior mesenteric vascular beds of anesthetized dogs. In the mesenteric circulation, 0.01 to 0.3 microgram of LTC4 and LTD4 reduced blood flow 20 to 60%. Effects were rapid in onset and flow returned to base line within 2 to 3 min. LTE4 was less potent in the mesenteric circulation and responses were not clearly dose dependent over the same range. In contrast, renal blood flow increased after injections of 3 and 10 micrograms of LTC4 and LTD4 into the renal artery. LTE4 did not influence renal blood flow significantly at these doses. Inhibition of prostaglandin synthesis did not alter responses to these LTs in either vascular bed, suggesting that endogenous prostaglandin synthesis did not mediate or modulate responses to the LTs. Mesenteric vascular responses to LTC4 and LTD4, but not LTE4, were inhibited by the LT receptor antagonist FPL-55712. Because LTs are released in a variety of immunological and inflammatory reactions, their differential effects may lead to a redistribution of peripheral blood flow in these reactions.