Effects of thromboxane synthase inhibitors on renal function

Summary 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 (UK 38,485; 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 OKY 1581 (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 UK 38,485 and OKY 1581 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.Send offprint requests to E. K. Jackson