Document Detail

Neurohormonal antagonism in heart failure; beneficial effects of vasopressin V(1a) and V(2) receptor blockade and ACE inhibition.
MedLine Citation:
PMID:  12062361     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To assess the long-term efficacy of vasopressin (AVP) V(1a) and V(2) 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 V(1a) and V(2) 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.
Mareo Naitoh; John Risvanis; Leanne C Balding; Colin I Johnston; Louise M Burrell
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cardiovascular research     Volume:  54     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-06-13     Completed Date:  2002-07-12     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  51-7     Citation Subset:  IM    
Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia.
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MeSH Terms
Analysis of Variance
Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
Arginine Vasopressin / blood
Atrial Natriuretic Factor / blood
Benzazepines / therapeutic use*
Blood Pressure / drug effects
Captopril / therapeutic use*
Heart Failure / drug therapy*,  pathology
Myocardium / pathology
Osmolar Concentration
Rats, Sprague-Dawley
Receptors, Vasopressin / antagonists & inhibitors*
Renin / blood
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Benzazepines; 0/Receptors, Vasopressin; 0/conivaptan; 113-79-1/Arginine Vasopressin; 62571-86-2/Captopril; 85637-73-6/Atrial Natriuretic Factor; EC
Comment In:
Cardiovasc Res. 2002 Apr;54(1):13-5   [PMID:  12062356 ]

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