PROLONGED STIMULATION OF INTRARENAL V-1 VASOPRESSIN RECEPTORS RESULTSIN SUSTAINED HYPERTENSION

In an earlier study, we reported that chronic intravenous administrati on of the V-1 agonist [Phe(2),Ile(3),Orn(8)]vasopressin (V(1)AG) resul ts in sustained hypertension. The present study was designed to determ ine whether V-1-induced hypertension may be related specifically to in trarenal actions of this peptide. Chronic infusion of the V-1 agonist into the medullary interstitial space of a single remaining kidney of normal, conscious Sprague-Dawley rats at the rate of 2 ng kg(-1).min(- 1) for 14 days resulted in a sustained rise of 18 mmHg of mean arteria l pressure (MAP). After withdrawal of V(1)AG, MAP returned to the base line level. During the first day of V(1)AG infusion, there was a net l oss of body sodium and no evidence of fluid retention throughout the p eriod of hypertension. Plasma osmolality, sodium and potassium concent ration, and water intake and body weight were not significantly affect ed by medullary interstitial infusion of V(1)AG. Renal medullary inter stitial infusion of an equimolar amount of arginine vasopressin (AVP) did not affect MAP. Chronic medullary interstitial infusion of the sel ective V-1 antagonist d(CH2)(5)[Tyr(Me)(2),Ala-NH29]AVP in equimolar a mounts (2.5 ng.kg(-1).min(-1)) prevented the MAP increase elicited by intravenous V(1)AG. However, intravenous administration of the V-1 ant agonist at the same rate together with V(1)AG (n = 7) failed to preven t hypertension. The results indicate that hypertension can be elicited by chronic stimulation of renal medullary V-1 vasopressin receptors. They also suggest that some V-2 agonistic properties of AVP may restri ct the hypertensive action of this hormone. The mechanism for the rise of arterial pressure remains to be determined.