Indomethacin blockade of renal PGE-synthesis: effect on total renal and tubular function and plasma renin concentration in hydropenic rats and on their response to isotonic saline

Abstract

The effects of indomethacin (I), a blocker of prostaglandin (PG)-synthetase, was studied in rats in an attempt to elucidate the physiological role of renal PGE. Plasma-I-concentrations of 13-14 mug/ml reduced renal venous plasma PGE-concentration significantly from 216 to 85 pg/ml within 45 min. Urine flow and solute excretion decreased by 42% and 20%, respectively, while urine osmolality increased 450 mOsm. Inulin clearance (CIN) and proximal reabsorption rate was unaffected, while renal plasma flow (RPF) decreased by 18%. Plasma renin concentration decreased slightly but significantly. An i.v. saline load equal to 1% b.wt. given to I-treated rats failed to elevate significantly either urine flow, solute excretion, CIN, RPF or proximal reabsorption rate, but plasma renin decreased further. The normal inverse relationship between plasma renin and proximal reabsorption rate was absent. The data are consistent with the concept that intrarenal PGE plays in adjustment of renal vascular resistance, and support the concept of a physiological role of intrarenal PGE in regulating salt and water excretion. The data do not support any major physiological role of PGE in regulating proximal tubular function.