Vulnerability of the thick ascending limb to glutathione depletion in rat kidney: effects of diuretics and indomethacin

AM Torres, JV Rodriguez and MM Elias

Departamento de Morfologia, Fisiologia y Farmacoloigia, Facultad de Ciencias Bioquimicas y Farmaceuticas, Conicet-Universidad Nacional de Rosario, Argentina.

Previous works supported the idea that the thick ascending limb of Henle was the target structure for glutathione (GSH) depletion effects. In order to obtain more evidence on this hypothesis, we compared GSH depletion effects with those of two loop diuretics: furosemide and ethacrynic acid. The submaximal tubular effects observed with furosemide were magnified when the kidneys were previously GSH depleted, but maximal tubular effects of furosemide were GSH independent. This last observation suggested that furosemide and GSH depletion have common sites or mechanisms of action. On the other hand, ethacrynic acid tubular effects were always magnified when the rats were GSH depleted. As it has been proposed that the renal actions of furosemide and ethacrynic acid are at least in part mediated by prostaglandins, another set of experiments was performed using indomethacin to examine the possible role of renal prostaglandins in GSH depletion effects. It was observed that indomethacin greatly improved tubular functions in GSH-depleted rats suggesting that an increase in prostaglandins levels should be involved in the renal defects observed during GSH depletion. All these data give additional support to the idea that the thick ascending limb cells may have a special sensitivity to the effects of GSH depletion probably mediated by prostaglandins.

Volume 250, Issue 1, pp. 247-253, 07/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics