Leukotrienes cause mesentric vasoconstriction and hemoconcentration in rats without activating thromboxane receptors

Abstract

Thromboxane A 2/prostaglandin H 2 (TP)-receptor activation has been reported to participate in some of the response to peptide leukotrienes (LT). We examined the effect of TP-receptor antagonism on LT-induced mesenteric vasoconstriction and hemoconcentration in anesthetized rats. The antagonist used in these studies, SQ 30,741, was shown to have high selectivity and potency for vascular TP-receptors in the rat. Arterial (i.a) injection of LTC 4 and D 4 elicited dose-dependent and transient reductions in mesenteric blood flow without changes in arterial blood pressure. These responses were unaffected by a dose of SQ 30,741 which produced ∼99% inhibition of similar responses to U-46,619. In contrast, LT-induced mesenteric vasoconstriction was inhibited ∼90% by two LT antagonists, LY 171,883 and SKF 104,353. In other experiments i.v. infusion of LTD 4 caused increases in hematocrit and reductions in arterial blood pressure that were not influenced by SQ 30,741. These data suggest that increases in mesenteric vascular resistance and hemoconcentration in response to LTs are not the result of TP-receptor activation.