CAPTOPRIL TREATMENT DOES NOT RESTORE EITHER THE RENAL OR THE ANF RELEASE RESPONSE DURING VOLUME EXPANSION IN MODERATE TO SEVERE HIGH-OUTPUTHEART-FAILURE

Objective: Atrial natriuretic factor (ANF) release and the renal respo nse to moderate volume expansion have been shown to be conserved in ra ts with a mild to moderate degree of high output heart failure (aortoc aval shunt). The aim of this study was to investigate whether these va riables are also conserved in animals with moderate to severe heart fa ilure induced by an aortocaval shunt. The effect of angiotensin conver ting enzyme (ACE) inhibition by captopril on these responses was also investigated. Methods: An aortocaval shunt was developed in Sprague-Da wley rats weighing 180-200 g; sham operated rats served as controls. T hree 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 we re started. Four weeks after surgery, haemodynamic variables, ANF rele ase, diuresis, and natriuresis were evaluated following a moderate vol ume expansion. Results: Mean arterial blood pressure was lower in shun t animals and still lower in the ACE inhibited group than in the sham operated controls. Central venous pressure and left ventricular end di astolic pressure (LVEDP) were significantly higher in untreated shunt rats than in their controls. ACE inhibition returned the raised centra l venous pressure, but not LVEDP, to control values. Shunt rats had lo wer baseline urinary sodium excretion (UNaV), urinary volume, and pack ed cell volume than their sham operated controls. ACE inhibition rever sed baseline urinary volume to control values. Baseline COOH terminal and HN2 terminal ANF were greatly increased in both treated and untrea ted shunt rats. Volume expansion was performed three times in consciou s animals at 15 min intervals with human plasma protein fraction. Its effect on LVEDP was similar in all three groups, but the increase in c entral venous pressure was much higher in untreated shunt animals. UNa V, urinary volume, and the release of COOH terminal and NH2 terminal A NF in response to volume expansion were blunted in both treated and un treated 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, th e latter presenting very significant cardiac hypertrophy. Conclusions: Aortocaval shunt animals with moderate to severe heart failure show a blunted ANF release and renal response to volume expansion, which, de spite significant haemodynamic improvement, are not restored by ACE in hibition.