ANTAGONISM OF THE EFFECTS OF CERTAIN STEROIDS ON THE RENAL EXCRETION OF WATER AND ELECTROLYTES BY 2-AMINO-4-(p-CHLORO-ANILINO)-s-TRIAZINE

¹ Department of Pharmacology and Toxicology, University of Wisconsin, Madison, Wisconsin

The effects of 2-amino-4-(p-chloroanilino)-s-triazine on the renal excretion of water and certain electrolytes have been studied in the rat. Following an oral load of isotonic sodium chloride it produces diuresis, natriuresis, chloruresis and retention of potassium. After similar large oral loads of water the natriuretic and chloruretic actions persist but antidiuresis and no significant change in potassium excretion are observed. The diuretic effect occurs after oral administration of water if the water load is decreased. The antidiuretic response is observed in hypophysectomized rats after large oral loads of water if normal handling of such loads is restored by administration of cortisone.

The effects of 2-amino-4-(p-chloroanilino)-s-triazine and theophylline on the renal excretion of water and electrolytes are sufficiently different to indicate that the presence of the —N—C—N— group in different compounds does not confer on them common diuretic properties.

Potassium excretion is suppressed by the triazine even when it is given in conjunction with an oral load of potassium or with acetazoleamide. The results with acetazoleamide suggest that it interferes with the distal tubular secretion of potassium.

Studies in adrenalectomized animals administered the triazine derivative and steroids suggest that the natriuretic effect of the drug may be due to an inhibition of the reabsorptive mechanisms for sodium which are regulated by the adrenal steroids. The reduced excretion of potassium in adrenalectomized animals suggests that a factor, other than antagonism of steroid action, operates with respect to the effect of the triazine on the renal excretion of this cation. Evidence which suggests that this triazine derivative is capable of antagonizing certain responses to adrenal cortical steroids is presented.