High-dose angiotensin-converting enzyme inhibition restores body fluid homeostasis in heart-transplant recipients

Objectives We tested the hypothesis that salt and fluid retention in heart-transplant recipients (HTRs) is caused by a failure to reflexively suppress the renin-angiotensin-aldosterone system (RAAS). Background It is known that extracellular fluid volume is expanded (12% to 15%) in HTRs who develop hypertension. Methods Responses to volume expansion were measured in eight HTRs (ages 57 ± 6 years) and six liver-transplant recipients (LTRs) (ages 52 ± 2 years) both before and after treatment with captopril (225 mg/day). After three days of a standardized diet, 0.154 mol/l saline was infused at 8 ml/kg/h for 4 h. Blood pressure, hormones, and renal function were monitored for 48 h. After four months, the same subjects received captopril (225 mg/day), and the protocol was repeated. Results Before captopril, saline infusion suppressed the RAAS in LTRs but not in HTRs, resulting in elimination of 86 ± 12% versus 50 ± 11% of the sodium load by 48-h postinfusion. Blood pressure increased only in the HTRs (+16 ± 5/9 ± 3 mm Hg) and remained elevated for 48 h (p ≤ 0.05). After captopril, sodium elimination was comparable in the liver (87 ± 13%) and heart groups (86 ± 12%) and blood pressure did not change in either group. Conclusions Heart transplant recipients have blunted diuretic and natriuretic responses to volume expansion that is mediated by their inability to suppress the RAAS. Pharmacologic suppression of the RAAS normalized defects in blood pressure and fluid homeostasis. These findings indicate that hypertension in HTRs is caused, in part, by a failure to reflexively suppress the RAAS when these patients become hypervolemic.