Arginine Vasopressin Increases Renal Sodium Excretion in the Anesthetized Rat Through V1 Receptors

Abstract

We have previously suggested that the increase in renal Na+ excretion in response to physiological doses of arginine vasopressin (AVP) is not directly linked to the V2-mediated antidiuretic effect. In the present study we investigated the possible involvement of AVP V1 receptors in this natriuresis using a specific AVP V1 antagonist [I-(β-mercapto-β,β-cyclopentamethylenepropionic acid), 2-O-methyltyrosine arginine vasopressin, d(CH2)5(Me)2]AVP, infused at a rate of 15 ng·min-1. Male anesthetized Sprague-Dawley rats were placed on a continuous jugular infusion of 0.077 M NaCl at 150 μL·min-1. After a 3-h equilibration period, samples were collected at 20-min intervals for 4 h for the determination of urine flow, and Na+ and K+ excretion rates. In those animals in which the effects of AVP were studied, a 1-h control period was allowed following which AVP was infused at 0.02–0.08 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. In other groups the AVP V1 antagonist d(CH2)5[Tyr(Me)2]AVP (15 ng · min-1) alone or in combination with AVP (at various dose rates) was also administered for 1 h 20 min. All dose rates of AVP produced an antidiuresis which was associated significantly to increased Na+ excretion rate. However, AVP administration at the median dose rate (0.04 pmol · min-1) significantly (p < 0.01) decreased the amount of urine voided by comparison with control animals (6.34 ± 1.05 mL vs. 11.892 ± 0.03 mL, n = 7) although the urinary Na+ was elevated (967 ± 18 μmol vs. 742 ± 81 μmol, n = 7). This AVP-induced increase in urinary Na+ loss was abolished in animals receiving combined AVP (0.04 pmol · min-1) and AVP V1 antagonist (674 ± 47 μmol, n = 7) although the antidiuretic effect persisted. Urine flow and Na+ excretion rates remained unchanged in groups of animals administered AVP V1 antagonist alone. In all groups, the K+ excretion rates did not significantly differ. It is concluded that the V1 receptor mediates the natriuretic effect of AVP.