V1-RECEPTOR AND V2-RECEPTOR CONTRIBUTIONS TO OVINE FETAL RENAL AND CARDIOVASCULAR-RESPONSES TO VASOPRESSIN

To assess the contributions of arginine vasopressin (AVP) V1- and V2-receptors to the ovine fetal responses to AVP, we studied V2-receptor stimulation in the presence of V1-receptor blockade, and selective V2-receptor stimulation in chronically catheterized fetal lambs. AVP administration (20 ng/kg) to the saline infused fetuses (n = 8; 132 +/- 2 days) significantly increased mean arterial pressure (MAP; 45 +/- 2 to 53 +/- 4 mmHg) and urine osmolality (U(osm); 134 +/- 13 to 379 +/- 42 mosmol/kgH2O) and decreased heart rate (HR; 168 +/- 3 to 147 +/- 5 beats/min) and urine flow (V; 0.48 +/- 0.10 to 0.19 +/- 0.03 ml/min). V1-receptor antagonist infusion, [d(CH2)5,Tyr(Me)]AVP (n = 7; 134 +/- 1 days) had no effect on fetal MAP, U(osm), HR, or V. V1-receptor blockade abolished the MAP response to AVP without affecting the HR and urinary responses. In a second series of animals (n = 6; 131 +/- 1 days), selective V2-receptor agonist infusion [desmopressin (DDAVP)] had no effect on fetal MAP or HR while initial changes in V and U(osm) were identical to the effects of AVP alone. Our results demonstrate clear discrimination of V1- and V2-receptor-mediated events in the fetal MAP and renal responses to AVP. Moreover, the HR response to AVP is not mediated by the population of V1-receptors blocked by [d(CH2)5,Tyr(Me)]AVP or V2-receptors stimulated by DDAVP, suggesting the presence of additional AVP receptor subclass(es) during fetal life.