Selective vasopressin inhibition in rats with heart failure decreases afterload and results in venodilatation

The hemodynamic effects of selective inhibition of arginine vasopressin (AVP) with a V₁ antagonist, (CH₂)₅yreAVP^a CL-1-4A, were studied in normal rats (n = 17) and in rats 4 weeks after coronary artery ligation with large myocardial infarctions and elevated left ventricular end-diastolic pressures (n = 22). In normal rats AVP inhibition with a 35-μg/kg bolus of AVP V₁ antagonist did not change heart rate, right atrial, left ventricular systolic, left ventricular end-diastolic or aortic pressures. There were also no changes in mean circulatory filling pressure, unstressed vascular volume, blood volume or venous compliance. In rats with infarction and elevated left ventricular end-diastolic pressures, AVP inhibition did not change heart rate, right atrial pressure, mean circulatory filling pressure or blood volume, but mean aortic pressure decreased from 103 ± 3 to 88 ± 2 mm Hg (P < .001), venous compliance increased (P < .001) from 2.17 ± 0.07 to 3.04 ± 0.11 ml/mm Hg/kg and unstressed vascular volume decreased from 42.3 ± 3.1 to 34.7 ± 2.6 ml/kg (P < .05). We conclude that inhibition of AVP with a specific V₁ antagonist had no effect on the venous or arterial circulations in normal rats, but in rats with left ventricular dysfunction and heart failure after chronic myocardial infarction, AVP inhibition decreased arterial pressure and caused venodilatation.