Effect of conivaptan, a combined vasopressin V1a and V2 receptor antagonist, on vasopressin-induced cardiac and haemodynamic changes in anaesthetised dogs

The neurohormonal factor arginine vasopressin (AVP) produces potent systemic vasoconstriction as well as water retention in the kidneys via the V-1a and V-2 receptors, respectively. Therefore, AVP may be considered as an aggravating factor of cardiac failure. In the present study, the effects of intravenous (i.v.) infusion of AVP on cardiovascular parameters and the effect of conivaptan (YM087, 4'- (2-methyl-1,4,5,6-tetrahydroimidazo [4,5-d] [1]benzoazepine-6-carbonyl)-2-phenylbenzanilide monohydrochloride), a vasopressin V-1a/V-2 receptor antagonist, on AVP-induced cardiac and haemodynamic changes were investigated in pentobarbitone-anaesthetised dogs. The i.v. infusion of AVP (0.12-4 mU kg(-1) min(-1)) dose-dependently produced decreases in the cardiac contractility indicator LV dP/dt(max), and cardiac output (CO) and increases in left ventricular end-diastolic pressure (LVEDP) and total peripheral resistance (TPR). These changes accurately mimic the cardiovascular symptoms of congestive heart failure. The i.v. bolus injection of conivaptan (0.1 mg kg(-1)) rapidly attenuated the AVP (4 mU kg(-1) min(-1))-induced decrease in CO and reversed the AVP-induced elevation in both LVEDP and TPR. In conclusion, i.v. infusion of AVP produced cardiac dysfunction and vasoconstriction in pentobarbitone-anaesthetised dogs. Conivaptan demonstrated the ability to dramatically improve the impaired cardiovascular parameters induced by AVR The results suggest the potential usefulness of conivaptan in treating congestive heart failure. (C) 2002 Elsevier Science Ltd. All rights reserved.