High dose angiotensin-converting enzyme inhibition prevents fluid volume expansion in heart transplant recipients

OBJECTIVES We sought to test the hypothesis that plasma Volume (PV) expansi on in heart transplant recipients (HTRs) is caused by failure to reflexivel y suppress the renin-angiotensin-aldosterone (RAA) axis. BACKGROUND Extracellular fluid volume expansion occurs in clinically stable HTRs who become hypertensive. We have previously demonstrated that the RAA axis is not reflexively suppressed by a hypervolemic stimulus in HTRs. METHODS Plasma volume and fluid regulatory hormones were measured in eight HTRs (57 +/- 6 years old) both before and after treatment with captopril (2 25 mg/day). Antihypertensive and diuretic agents were discontinued 10 days before. The HTRs were admitted to the Clinical Research Center (CRC), and, after three days of a constant diet containing 87 mEq/day of Na+, PV was me asured by using the modified Evans blue dye dilution technique. After appro ximately four months (16 +/- 5 weeks), the same HTRs again discontinued all antihypertensive and diuretic agents; they were progressed to a captopril dose of 75 mg three times per day over 14 days, and the CRC protocol was re peated. RESULTS Captopril pharmacologically suppressed (p < 0.05) supine rest level s of angiotensin II (-65%) and aldosterone (-75%). The reductions in vasopr essin and atrial natriuretic peptide levels after captopril did not reach s tatistical significance. The PV, normalized for body weight (ml/kg), was si gnificantly reduced by 12% when the HTRs received captopril. CONCLUSIONS Extracellular fluid volume is expanded (12%) in clinically stab le HTRs who become hypertensive. Pharmacologic suppression of the RAA axis with high-dose captopril (225 mg/day) returned HTRs to a normovolemic state . These findings indicate that fluid retention is partly engendered by a fa ilure to reflexively suppress the RAA axis when HTRs become hypervolemic. ( C) 2000 by the American College of Cardiology.