Leukotrienes cause mesenteric vasoconstriction and hemoconcentration in rats without activating thromboxane receptors.
Thromboxane A2/prostaglandin H2 (TP)-receptor activation has been reported to participate in some of the responses 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 LTC4 and D4 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 approximately 99% inhibition of similar responses to U-46,619. In contrast, LT-induced mesenteric vasoconstriction was inhibited approximately 90% by two LT antagonists, LY 171,883 and SKF 104,353. In other experiments i.v. infusion of LTD4 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.
Schumacher
W A
WA
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, NJ 08543-4000.
Heran
C L
CL
Allen
G T
GT
Ogletree
M L
ML
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000098:Acetophenones / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003998:Dicarboxylic Acids / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D006400:Hematocrit; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000502:physiology*; D017482:Receptors, Thromboxane; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D000098:Acetophenones; D003998:Dicarboxylic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013189:SRS-A; D013777:Tetrazoles; C054215:SQ 30741; D000804:Angiotensin II; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C044660:LY 171883; D015237:Dinoprost; C052393:pobilukast