Effects of chronic AVP V2R blockade in congestive heart failure in sheep - Comparison with chronic ACE inhibition

Abstract

The chronic effects of AVP V2 receptor (V2R) antagonism or ACE inhibition in conscious sheep with congestive heart failure (CHF) using the non-peptide V2R antagonist, OPC-31260 (1), and the ACE inhibitor, ramipril, were examined. Fifteen ovarectomised ewes equipped with epicardial right ventricular pacing leads and transonic cardiac output (CO) flow probe, had rapid ventricular pacing until the animal developed CHF. Then animals received oral OPC-31260 (10mg/kg twice daily, n=5), ramipril (1mg/kg daily, n=5) or vehicle (n=5) for 8 days. Throughout the experiment, animals were allowed free tap water. Oral OPC-31260 produced significant water diuresis, significant increase in CO (△CO; +0.92 L/..