Grove L, Christensen P, Bie P
Department of Medical Physiology, University of Copenhagen, Denmark.
Acta Physiol Scand. 1998 May;163(1):93-101. doi: 10.1046/j.1365-201x.1998.00332.x.
Vasopressin--but not the V2 receptor agonist [deamino-cis1,D-Arg8]-vasopressin (dDAVP)--may mediate natriuresis in dogs. The present study investigated this phenomenon by use of nonpeptide antagonists to V1a and V2 receptors 1-¿1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl¿-3,4-dihydro-2 (1H)-quinolinone (OPC-21268) and 5-dimethylamino-1-¿4-(2-methylbenzoylamino)-benzoyl¿-2,3,4,5-tetra hydro-1 H-benzazepine (OPC-31260), respectively) hypothesising that only V1a inhibition would reduce the natriuresis. In conscious dogs vasopressin secretion was suppressed by water loading (2% body weight) and replaced by infusion of vasopressin (50 pg min-1 kg-1) resulting in physiological plasma concentrations (plasma levels of AVP (pAVP) = 2.0 +/- 0.1 pg mL-1). In this setting, OPC-21268 did not change the rate of sodium excretion. OPC-31260 increased water excretion 12-fold without significant changes in sodium excretion. Heart rate, mean arterial blood pressure, glomerular filtration rate, and clearance of endogenous Li+ were unchanged. During vasopressin infusion, both antagonists increased pAVP, OPC-21268 by 20% and OPC-31260 by 100% (2.0 +/- 0.2-4.0 +/- 0.3 pg mL-1). In the absence of vasopressin infusion, OPC-31260 did not increase pAVP. Thus, the increase in pAVP appeared to be due to a decrease in metabolic clearance rate. The results indicate that the present dose of V1a receptor inhibitor OPC-21268 does not reduce sodium excretion and that both vasopressin antagonists inhibit vasopressin metabolism.
