Renal vasoconstriction with U-46,619; role of arachidonate metabolites.
Thromboxane A2 (TxA2) or its stable mimetic U-46,619 can increase the generation of arachidonate metabolites. Therefore, these studies were designed to investigate the role of prostaglandins, TxA2, and leukotrienes in the renal vascular response to U-46,619. Anesthetized rats were studied during a basal period and during an intra-aortic infusion of vehicle or U-46,619 (1 micrograms/kg per minute). U-46,619 reduced the GFR and the RBF without changing the mean arterial pressure or the femoral vascular resistance. All of the effects of U-46,619 were blocked by pretreatment with the TxA2/prostaglandin H2 receptor antagonist SQ-29,548. Pretreatment with the cyclo-oxygenase inhibitor indomethacin did not modify the renal vascular response to U-46,619. However, pretreatment with the TxA2 synthesis inhibitor UK-38,485 or with the leukotriene D4/E4 antagonist LY-163,443 markedly blunted the U-46,619-induced increase in renal vascular resistance and the decrease in GFR. These results indicate that the renal vascular response to U-46,619 is receptor mediated and is promoted by TxA2 and leukotriene D4/E4.
Department of Medicine, Pharmacology, and Therapeutics, University of Florida, College of Medicine, Gainesville.
C S
CS
Wilcox
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Folger
W J
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Welch
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006834:Hydrazines / Q000494:pharmacology; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D015289:Leukotrienes; D011450:Prostaglandin Endoperoxides, Synthetic; D016718:Arachidonic Acid; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548