Neutral endopeptidase inhibition increased circulating endothelin-1 (P<0.01) and ANP (P<0.01) without adversely affecting systemic or renal hemodynamics in heart transplant patients.
RCT (n=7)
Double-blind
Does acute neutral endopeptidase (NEP) inhibition alter hemodynamic, renal, and hormonal responses in chronic, stable heart transplant patients?
Acute NEP inhibition in stable heart transplant patients increases ANP and promotes natriuresis and diuresis without adverse systemic or renal hemodynamic effects, despite an increase in endothelin-1.
p-value: p=<0.01
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.
Piquard et al. (Thu,) conducted a rct in Chronic, stable heart transplant (n=7). Neutral endopeptidase (NEP) inhibition vs. Placebo was evaluated on Circulating endothelin-1 (p=<0.01). Neutral endopeptidase inhibition increased circulating endothelin-1 (P<0.01) and ANP (P<0.01) without adversely affecting systemic or renal hemodynamics in heart transplant patients.