Indomethacin impairs water diuresis in the DI rat: role of prostaglandins independent of ADH

Abstract

The mechanisms by which endogenous renal prostaglandins regulate H2O excretion were investigated. Inhibition of prostaglandin synthesis slowed H2O diuresis in H2O loaded unanesthetized Sprague-Dawley rats, and in Brattleboro rats with hereditary diabetes insipidus owing to absence of endogenous vassopressin. In both strains, treatment with indomethacin or meclofenamate increased the osmolality of the renal papilla by raising Na and urea content, and also increased the osmolality of the urine. Endogenous creatinine clearance and solute excretion were unchanged. The data are consistent with an effect of prostaglandins on solute transport by renal tubules and demonstrate that endogenous prostaglandins influence H2O excretion by a mechanism independent of the presence of antidiuretic hormone.