Kinter L B, Churchill S, Stassen F L, Moore M, Huffman W
J Pharmacol Exp Ther. 1987 Jun;241(3):797-803.
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.
在松鼠猴（Saimiri sciureus）这一灵长类动物中，腹腔注射或静脉注射加压素拮抗剂后，可观察到加压素拮抗作用和水利尿（水清除）现象。在体外评估了加压素刺激的肾髓质腺苷酸环化酶活性的拮抗作用；最有效的拮抗剂是在第2位具有D-酪氨酸（烷基）取代的那些。在体内评估了水清除作用；最有效的利水剂同样是在第2位具有D-酪氨酸（烷基）取代的那些。一系列拮抗剂的体外加压素拮抗剂活性与体内利水活性之间的相关性为r = 0.7880（P小于0.05）。随着加压素拮抗剂剂量的增加，电解质、肌酐和尿素的肾排泄量略有增加的趋势；溶质排泄率接近但很少超过松鼠猴中与水利尿相关的排泄率。加压素拮抗剂在体内拮抗外源性加压素的抗利尿活性。静脉注射去甘氨酰（CH2）5D-酪氨酸（乙基）加压素（desGlyd(CH2)5D-Tyr(Et)VAVP）后，利水反应的起效时间在30分钟内；持续时间超过120分钟。这些研究证实了在灵长类动物中与加压素拮抗剂给药相关的加压素拮抗作用和水清除作用。
