Effects of thromboxane synthase inhibitors on renal function

Area of Science:

• Nephrology
• Pharmacology
• Physiology

Background:

• Thromboxane A2 (TXA2) has effects on renal function opposite to other prostanoids.
• TXA2 synthase inhibitors may alter renal function by reducing TXA2 production or increasing prostaglandin biosynthesis.
• The study investigated the impact of TXA2 synthase inhibition on renal function during hypotension.

Purpose of the Study:

• To test the hypothesis that TXA2 synthase inhibitors alter renal function by reducing TXA2 production and/or increasing prostaglandin biosynthesis.
• To compare changes in renal function induced by suprarenal aortic constriction in dogs pretreated with TXA2 synthase inhibitors or vehicle.

Main Methods:

• Anesthetized dogs underwent suprarenal aortic constriction.
• Dogs were pretreated with either a TXA2 synthase inhibitor (UK38,485 or OKY1581) or a vehicle.
• Renal function parameters including hemodynamics, glomerular filtration, and electrolyte excretion were measured.

Main Results:

• TXA2 synthase inhibitors did not significantly alter mean arterial blood pressure, heart rate, renal blood flow, renal vascular resistance, glomerular filtration, or electrolyte excretion.
• Both inhibitors appeared to attenuate the increase in renal renin secretion rate induced by suprarenal aortic constriction.
• No significant changes were observed in renal artery hypotension-induced changes in renal hemodynamics or electrolyte excretion.

Conclusions:

• Acute administration of TXA2 synthase inhibitors does not modify acute renal artery hypotension-induced changes in electrolyte excretion or renal hemodynamics.
• Acute TXA2 inhibition attenuates increases in renin release during suprarenal aortic constriction in dogs via unknown mechanisms.