V1- 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 (Uosm; 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, Uosm, 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 Uosm 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.
Ervin
M G
MG
Department of Obstetrics and Gynecology, University of California, Los Angeles, School of Medicine, Torrance 90502.
Ross
M G
MG
Leake
R D
RD
Fisher
D A
DA
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D002319:Cardiovascular System / Q000196:embryology*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D005314:Embryonic and Fetal Development; D005333:Fetus / Q000187:drug effects*; D007262:Infusions, Intravenous; D007668:Kidney / Q000196:embryology*; D011945:Receptors, Angiotensin / Q000502:physiology*; D017483:Receptors, Vasopressin; D012756:Sheep; D014667:Vasopressins / Q000494:pharmacology*
D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D014667:Vasopressins; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D003894:Deamino Arginine Vasopressin