Effect of prostaglandin synthesis inhibition on the tubuloglomerular feedback control in the rat kidney.

Abstract

It is known that intact prostaglandin synthesis is of some importance for tubuloglomerular feedback (TGF). In this study the effects of cyclooxygenase inhibition by oral fenflumizole, an imidazole derivative, on TGF in rats after acute elevation of ureteral pressure were investigated by comparison with the TGF mechanism in untreated rats. The effects of fenflumizole on the TGF mechanism were also compared with those of indomethacin injection. To characterize the TGF mechanism proximal tubular stop-flow pressure (Psf) was measured during perfusion of the loop of Henle with an artificial perfusion solution with a composition resembling that of the proximal fluid. The perfusion rate was varied from 0 to 40 nl.min-1, in steps of 2.5-5 nl.min-1, permitting measurement of the maximal pressure response delta Psf, to increased tubular perfusion, and the perfusion rate which elicited a half-maximal drop in Psf, designated the turning point (TP). Both cyclooxygenase inhibitors caused a significant increase in TP from a control value of 21 to approximately 27 nl.min-1. TP remained at this level in fenflumizole-treated rats, even after elevation of ureteral pressure, a situation in which TGF is normally not detectable. From these and earlier investigations we conclude that the prostaglandin system is of importance for a normally operating TGF control mechanism, both under normal conditions and, especially, in conditions in which resetting of TGF is observed.