Vasopressin antagonism in the squirrel monkey (Saimiri sciureus)

LB Kinter, S Churchill, FL Stassen, M Moore and W Huffman

Vasopressin antagonism and water diuresis (aquaresis) is demonstrated after i.p. or i.v. administration of vasopressin antagonists in a primate species, the squirrel monkey (Saimiri sciureus). Antagonism of vasopressin-stimulated renal medullary adenylate cyclase activity was evaluated in vitro; the most potent antagonists were those with D- tyrosine (alkyl) substitutions at position 2. Aquaresis was evaluated in vivo; the most potent aquaretic agents were again those with D- tyrosine (alkyl) substitutions at position 2. Correlation of in vitro vasopressin antagonist and in vivo aquaretic potencies for a series of antagonists was r = 0.7880 (P less than .05). Renal excretion of electrolytes, creatinine and urea tended to increase slightly as a function of vasopressin antagonist dose; the rates of solute excretion approached but seldom exceeded those rates associated with water diuresis in squirrel monkeys. The vasopressin antagonists antagonized the antidiuretic activity of exogenous vasopressin in vivo. Onset of the aquaretic response to i.v. administration of desGlyd(CH2)5D- Tyr(Et)VAVP was within 30 min; duration was greater than 120 min. These studies establish vasopressin antagonism and aquaresis associated with administration of vasopressin antagonists in a primate species.

Volume 241, Issue 3, pp. 797-803, 06/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				D. P. Brooks, M. Valente, G. Petrone, P. D. Depalma, M. Sbacchi, and G. D. Clarke Comparison of the Water Diuretic Activity of Kappa Receptor Agonists and a Vasopressin Receptor Antagonist in Dogs J. Pharmacol. Exp. Ther., March 1, 1997; 280(3): 1176 - 1183. [Abstract] [Full Text]