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Cardiovascular Research 2002 54(1):51-57; doi:10.1016/S0008-6363(02)00244-4
© 2002 by European Society of Cardiology
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Copyright © 2002, European Society of Cardiology

Neurohormonal antagonism in heart failure; beneficial effects of vasopressin V1a and V2 receptor blockade and ACE inhibition

Mareo Naitoh, John Risvanis, Leanne C. Balding, Colin I. Johnston and Louise M. Burrell*

Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia

burrell{at}austin.unimelb.edu.au

* Corresponding author. Tel.: +61-3-9496-5477; fax: +61-3-9457-5485

Objective: To assess the long-term efficacy of vasopressin (AVP) V1a and V2 receptor blockade with conivaptan, alone and in combination with angiotensin converting enzyme (ACE) inhibition on blood pressure, metabolic and neurohormonal parameters, and cardiovascular structure in a rat model of congestive heart failure (CHF). Methods: CHF was induced by left coronary artery ligation. CHF rats received conivaptan (1 mg/kg/day), ACE inhibition (captopril, 50 mg/kg/day), conivaptan and captopril (Combination) or vehicle for 4 weeks. Blood pressure was measured weekly, metabolic caging studies performed at 25 days, and rats killed and blood and tissue collected after 4 weeks treatment. Results: Combination treatment lowered blood pressure (P<0.01), and conivaptan and Combination caused an aquaresis (P<0.01). Combination decreased plasma natriuretic peptide (P<0.05), reduced left and right ventricular mass (P<0.01) and lung mass (P<0.05). Conclusions: In CHF, blockade of vasopressin V1a and V2 receptors was associated with increased water excretion, and the combination of conivaptan with ACE inhibition was the only treatment to reduce blood pressure, natriuretic peptide and pulmonary congestion. These results suggest conivaptan may be a useful addition to ACE inhibitors in the management of vasoconstriction and fluid retention that characterizes CHF.

KEYWORDS ACE inhibitors; Blood pressure; Heart failure; Natriuretic peptide


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