Effects of receptor blockade on metabolism and renal actions of vasopressin in conscious dogs.
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.
Grove
L
L
Department of Medical Physiology, University of Copenhagen, Denmark.
Christensen
P
P
Bie
P
P
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000502:physiology; D006728:Hormones / Q000097:blood; D007668:Kidney / Q000187:drug effects*; D009318:Natriuresis / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D012997:Solvents / Q000494:pharmacology; D014667:Vasopressins / Q000378:metabolism* / Q000494:pharmacology*
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D006728:Hormones; D010880:Piperidines; D015363:Quinolones; D012997:Solvents; D014667:Vasopressins; C068644:OPC 21268; C076251:mozavaptan; D004121:Dimethyl Sulfoxide