RT Journal Article
SR Electronic
T1 Vasopressin antagonism in the squirrel monkey (Saimiri sciureus).
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 797
OP 803
VO 241
IS 3
A1 L B Kinter
A1 S Churchill
A1 F L Stassen
A1 M Moore
A1 W Huffman
YR 1987
UL http://jpet.aspetjournals.org/content/241/3/797.abstract
AB 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.