Hormonal, renal, hemodynamic responses to acute neutral endopeptidase inhibition in heart transplant patients

Abstract

We investigated the hemodynamic, renal, and hormonal responses to neutral endopeptidase (NEP) inhibition during a 6-h, double-blind, randomized, placebo-controlled study in seven chronic, stable heart transplant patients. Baseline characteristics were similar during both experiments, and no significant changes were observed after placebo. NEP inhibition increased circulating endothelin-1 (from 2.01 ± 0.1 to 2.90 ± 0.2 pmol/l; P < 0.01), atrial natriuretic peptide (ANP; from 21.5 ± 2.7 to 29.6 ± 3.7 pmol/l; P < 0.01), and the ANP second messenger cGMP. Noteworthy, systemic blood pressure did not increase. Renal plasma flow and glomerular filtration rate remained unmodified after NEP inhibition. Filtration fraction (33 ± 13%), diuresis (196 ± 62%), and natriuresis (315 ± 105%) increased significantly in relation to ANP and cGMP. A strong inverse relationship was observed between excreted cGMP and sodium reabsorption ( r = −0.71, P < 0.0001). Thus, despite significantly increasing endothelin-1, NEP inhibition did not adversely influence systemic or renal hemodynamics in transplant patients. ANP, possibly through a tubular action, enhances the natriuresis observed after NEP inhibition.