ARGININE-VASOPRESSIN INCREASES RENAL SODIUM-EXCRETION IN THE ANESTHETIZED RAT THROUGH V-1 RECEPTORS

We have previously suggested that the increase in renal Na+ excretion in response to physiological doses of arginine vasopressin (AVP) is no t directly linked to the V-2-mediated antidiuretic effect In the prese nt study we investigated the possible involvement of AVP V-1 receptors in this natriuresis using a specific AVP V-1 antagonist ta-mercapto-b eta,beta-cyclopentamethylenepropionic acid), 2-O-methyltyrosine argini ne vasopressin, d(CH2)(5)[Tyr(Me)(2)]AVP, infused at a rate of 15 ng . min(-1). Male anesthetized Sprague-Dawley rats were placed on a conti nuous jugular infusion of 0.077 M NaCl at 150 mu L . min(-1). After a 3-h equilibration period, samples were collected at 20-min intervals f or 4 h for the determination of urine flow and Na+ and K+ excretion ra tes. In those animals in which the effects of AVP were studied, a 1-h control period was allowed following which AVP was infused at 0.02-0.0 8 pmol . min(-1) for 1 h 20 min in separate groups of animals and then returned to the infusate alone for the last part of the experiment. I n other groups the AVP V-1 antagonist d(CH2)(5)[Tyr(Me)(2)]AVP (15 ng . min(-1)) alone or in combination with AVP (at various dose rates) wa s also administered for 1 h 20 min. All dose rates of AVP produced an antidiuresis which was associated significantly to increased Na+ excre tion rate. However, AVP administration at the median dose rate (0.04 p mol . min(-1)) significantly (p < 0.01) decreased the amount of urine voided by comparison with control animals (6.34 +/- 1.05 mt vs. 11.892 +/- 0.03 mt, n = 7) although the urinary Na+ was elevated (967 +/- 18 mu mol vs. 742 +/- 81 mu mol, n = 7). This AVP-induced increase in ur inary Na+ loss was abolished in animals receiving combined AVP (0.04 p mol . min(-1)) and AVP V-1 antagonist (674 +/- 47 mu mol, n = 7) altho ugh the antidiuretic effect persisted Urine flow and Na+ excretion rat es remained unchanged in groups of animals administered AVP V-1 antago nist alone. in all groups, she K+ excretion rates did not significantl y differ It is concluded that the V-1 receptor mediates the natriureti c effect of AVP.