Protection from hypoxemia-induced renal dysfunction by the thiophosphate WR-2721.

Abstract

The acute renal effects of hypoxemia-reoxygenation and the putative protective action of WR-2721 [S-, 2-(3-aminopropyl-amino)-, etylphosphosphorothioic acid], a drug with specific properties such as PTH-secretion inhibiting, calcium lowering and free radical scavenging activities, were investigated in anesthetized-ventilated rabbits. Glomerular filtration rate (GFR) and renal blood flow (RBF) were assessed by the clearance of inulin and para-aminohippuric acid, respectively. Each animal acted as its own control. Normoxemic control rabbits showed no changes in renal hemodynamics and function during 150 minutes. The administration of WR-2721 (75 mg/kg body wt i.v.) to normoxemic animals induced a significant decrease in MBP, RBF and diuresis, without affecting GFR. It significantly reduced plasma levels of PTH, decreased calcemia and increased urinary calcium excretion. In untreated hypoxemic-reoxygenated rabbits, 45 minutes of severe hypoxemia (PO2 around 35 mm Hg) induced a significant fall in MBP, GFR, RBF and diuresis, which persisted during the 60-minute reoxygenation period. The administration of WR-2721 before hypoxemia or reoxygenation prevented the hypoxemia-induced decrease in GFR and diuresis. Filtration fraction increased significantly. The renal functional improvement observed in hypoxemic rabbits administered WR-2721 could be mediated by its effect on calcium metabolism and/or its oxygen free radical scavenging properties.