Effect of thromboxane inhibition on tubuloglomerular feedback in hydronephrotic kidneys

The tubuloglomerular feedback (TGF) system is less sensitive after extracellular volume expansion (VE). In rats with partial ureteral obstruction, however, we have previously found increased TGF sensitivity during such expansion. Thromboxane A2 (TXA2) has been reported to be increased in the hydronephrotic kidney, and the present study was undertaken to investigate whether TXA2 might be responsible for these findings. The TGF characteristics were studied, by means of the stop-flow technique, in control and hydronephrotic rats before and after intravenous injection of either a thromboxane synthetase inhibitor or a thromboxane receptor antagonist during hydropenia. After VE, TGF was studied again. Proximal tubular stop-flow pressure (Psf) was measured during perfusion of the loop of Henle with a modified Ringer's solution, the maximal response (delta Psf) to an increased tubular flow rate was determined and the tubular perfusion rate which elicited a half-maximal decrease in Psf, designated the turning point, was recorded. In hydropenic control or hydronephrotic animals, TXA2 did not permanently change the TGF characteristics. During VE of the TXA2-blocked hydronephrotic animals, blocked both with synthetase inhibitor or receptor-antagonist, TGF was reset to a lower sensitivity like VE controls, as indicated by a high turning point and a low delta Psf. It was therefore concluded that thromboxane A2 inhibition does not influence the TGF system in hydropenia, but that the production of thromboxane A2 is responsible for the resetting of the TGF system during VE in hydronephrotic animals.