PROLONGED STIMULATION OF INTRARENAL V-1 VASOPRESSIN RECEPTORS RESULTS IN SUSTAINED HYPERTENSION

In an earlier study, we reported that chronic intravenous administration of the V-1 agonist [Phe(2),Ile(3),Orn(8)]vasopressin (V(1)AG) results in sustained hypertension. The present study was designed to determine whether V-1-induced hypertension may be related specifically to intrarenal 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 arterial pressure (MAP). After withdrawal of V(1)AG, MAP returned to the baseline level. During the first day of V(1)AG infusion, there was a net loss of body sodium and no evidence of fluid retention throughout the period of hypertension. Plasma osmolality, sodium and potassium concentration, and water intake and body weight were not significantly affected by medullary interstitial infusion of V(1)AG. Renal medullary interstitial infusion of an equimolar amount of arginine vasopressin (AVP) did not affect MAP. Chronic medullary interstitial infusion of the selective V-1 antagonist d(CH2)(5)[Tyr(Me)(2),Ala-NH29]AVP in equimolar amounts (2.5 ng.kg(-1).min(-1)) prevented the MAP increase elicited by intravenous V(1)AG. However, intravenous administration of the V-1 antagonist at the same rate together with V(1)AG (n = 7) failed to prevent 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 restrict the hypertensive action of this hormone. The mechanism for the rise of arterial pressure remains to be determined.