Neurohormonal antagonism in heart failure; beneficial effects of vasopressin V(1a) and V(2) receptor blockade and ACE inhibition.
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.
Naitoh
Mareo
M
Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia.
Risvanis
John
J
Balding
Leanne C
LC
Johnston
Colin I
CI
Burrell
Louise M
LM
D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D001552:Benzazepines / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; C106389:conivaptan; D001127:Arginine Vasopressin; D009320:Atrial Natriuretic Factor; D002216:Captopril; D012083:Renin