STUDIES ON THE RENAL PHARMACOLOGY OF DIAZOX1DE, AN ANTIDIURETIC BENZOTHIADIAZINE

¹ Department of General Pharmacology, Biological Research Division, Schering Corporation, Bloomfield, New Jersey

The effects of diazoxide on renal hemodynamics and excretory function have been examined in the normotensive rat and dog. In both species given single saline or water loads, a marked decrease in urine volume, sodium and chloride excretion was observed following oral (loses of diazoxide. In the rat, creatinine clearance was unaltered whereas PAH clearance was lowered in both species. The latter effect was due, in part, to an altered extraction of PAH caused by competition between diazoxide and PAH for the same transport system.

During sustained water diuresis in dogs, diazoxide markedly diminished free water clearance and increased total solute excretion. These effects were not observed in diabetes insipidus dogs. In dogs undergoing osmotic diuresis, the major effect of diazoxide was to reduce sodium chloride excretion.

It is suggested that the action of (liazoxide on renal excretory function depends upon the prevailing experimental conditions and may be effected through a direct tubular action, ADH release or renal and systemic hemodynarnic changes.