title: Effects of thromboxane synthase inhibitors on renal function.
abstract: In general the effects of thromboxane A2(TXA2) on renal function are opposite those produced by other prostanoids. TXA2 synthase inhibitors decrease the biosynthesis of TXA2 and may increase the production of other prostanoids by causing endoperoxide shunting. Therefore, in situations of increased kidney arachidonate mobilization, inhibition of renal TXA2 synthase might alter renal function by reducing TXA2 production and/or increasing prostaglandin (PG) biosynthesis. This hypothesis was tested by comparing the changes in renal function induced by suprarenal aortic constriction in anesthetized dogs pretreated with either a TXA2 synthase inhibitor (UK38,485; n = 7 or OKY1581; n = 7) or vehicle (0.1 M Na2CO3; n = 9). Several renal function parameters were compared in control versus treated animals by analysis of variance. Neither UK38,485 (1 mg/kg, i.v.) nor OKY1581 (10 mg/kg, i.v.) significantly altered renal artery hypotension-induced changes in mean arterial blood pressure, heart rate, renal blood flow, renal vascular resistance, glomerular filtration, filtration fraction, urine flow rate, sodium excretion rate, fractional sodium excretion, potassium excretion, or fractional potassium excretion. However, both UK38,485 and OKY1581 seemed to attenuate the increase in renal renin secretion rate induced by suprarenal aortic constriction. We conclude that acute administration of TXA2 synthase inhibitors does not modify acute renal artery hypotension-induced changes in either electrolyte excretion or renal hemodynamics. However, acute administration of TXA2 inhibitors attenuates suprarenal aortic constriction-induced increases in renin release in anesthetized dogs by unknown mechanisms.
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors.forename: E K
authors.initials: EK
authors.lastname: Jackson
authors.forename: F
authors.initials: F
authors.lastname: Goto
authors.forename: H D
authors.initials: HD
authors.lastname: Uderman
authors.forename: R J
authors.initials: RJ
authors.lastname: Workman
authors.forename: W A
authors.initials: WA
authors.lastname: Herzer
authors.forename: G A
authors.initials: GA
authors.lastname: FitzGerald
authors.forename: R A
authors.initials: RA
authors.lastname: Branch
mesh_terms: D000179:Acrylates / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D004285:Dogs; D004573:Electrolytes / Q000652:urine; D005260:Female; D006439:Hemodynamics; D007022:Hypotension / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D012083:Renin / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D000179:Acrylates; D001095:Arachidonic Acids; D004573:Electrolytes; D007093:Imidazoles; D008689:Methacrylates; C039242:dazmegrel; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D012083:Renin; D013930:Thromboxane-A Synthase