EFFECTS OF RENAL MEDULLARY INFUSION OF A VASOPRESSIN V-1 AGONIST ON RENAL ANTIHYPERTENSIVE MECHANISMS IN RABBITS

The factors responsible for the development of hypertension during chr onic activation of intrarenal V-1 receptors are unknown. We therefore tested whether medullary interstitial infusion of the selective V-1-re ceptor agonist [Phe(2),Ile(3),Orn(8)]-vasopressin (V-1 agonist) influe nces renal antihypertensive mechanisms initiated by increased renal pe rfusion pressure (RPP). In intact anesthetized rabbits, the V-1 agonis t (10 ng.kg(-1).min(-1)) reduced medullary perfusion by 36 +/- 7%, whe reas cortical perfusion was reduced by only 14 +/- 2%. An extracorpore al circuit was used to increase RPP in a stepwise manner from 65 to 85 , 110, 130, and 160 mmHg for consecutive 20-min periods. Increased RPP reduced mean arterial pressure by 35 +/- 8% in vehicle-treated rabbit s, but by only 10 +/- 3% in V-1 agonist-treated rabbits. Simultaneousl y, pressure-diuresis-natriuresis was induced; urine flow and sodium ex cretion increased similarly in the two groups of rabbits, but hematocr it did not change. We suggest that the depressor response to increased RPP is mainly due to release of a putative renal medullary depressor hormone (RMDH). Suppression of the release and/or actions of RMDH may therefore contribute to the hypertensive effect of chronic V-1 recepto r activation.