Captopril treatment does not restore either the renal or the ANF release response during volume expansion in moderate to severe high output heart failure

Abstract

Atrial natriuretic factor (ANF) release and the renal response to moderate volume expansion have been shown to be conserved in rats with a mild to moderate degree of high output heart failure (aortocaval shunt). The aim of this study was to investigate whether these variables are also conserved in animals with moderate to severe heart failure induced by an aortocaval shunt. The effect of angiotensin converting enzyme (ACE) inhibition by captopril on these responses was also investigated. An aortocaval shunt was developed in Sprague-Dawley rats weighing 180-200 g; sham operated rats served as controls. Three weeks after surgery, three experimental groups were established: aortocaval shunt and sham operated controls, and aortocaval shunt rats treated with captopril during the last week before the experiments were started. Four weeks after surgery, haemodynamic variables, ANF release, diuresis, and natriuresis were evaluated following a moderate volume expansion. Mean arterial blood pressure was lower in shunt animals and still lower in the ACE inhibited group than in the sham operated controls. Central venous pressure and left ventricular end diastolic pressure (LVEDP) were significantly higher in untreated shunt rats than in their controls. ACE inhibition returned the raised central venous pressure, but not LVEDP, to control values. Shunt rats had lower baseline urinary sodium excretion (UNaV), urinary volume, and packed cell volume than their sham operated controls. ACE inhibition reversed baseline urinary volume to control values. Baseline COOH terminal and HN2 terminal ANF were greatly increased in both treated and untreated shunt rats. Volume expansion was performed three times in conscious animals at 15 min intervals with human plasma protein fraction. Its effect on LVEDP was similar in all three groups, but the increase in central venous pressure was much higher in untreated shunt animals. UNaV, urinary volume, and the release of COOH terminal and NH2 terminal ANF in response to volume expansion were blunted in both treated and untreated shunt rats when compared with their sham operated counterparts. Both absolute and relative heart weights were significantly lower in captopril treated shunt animals than in the untreated shunt group, the latter presenting very significant cardiac hypertrophy. Aortocaval shunt animals with moderate to severe heart failure show a blunted ANF release and renal response to volume expansion, which, despite significant haemodynamic improvement, are not restored by ACE inhibition.