Hormonal, renal, hemodynamic responses to acute neutral endopeptidase inhibition in heart transplant patients.
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
François
F
Laboratoire des Régulations Physiologiques et des Rythmes Biologiques chez l'Homme, Equipe d'Accueil 3072, Université Louis Pasteur, 67085 Strasbourg, France. Francois.Piquard@physio-ulp.u-strasbg.fr
Richard
Ruddy
R
Charloux
Anne
A
Doutreleau
Stephane
S
Hannedouche
Thierry
T
Brandenberger
Gabrielle
G
Geny
Bernard
B
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D016572:Cyclosporine / Q000097:blood; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood; D005919:Glomerular Filtration Rate / Q000187:drug effects; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000008:administration & dosage*; D012079:Renal Circulation / Q000187:drug effects; D015244:Thiorphan / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D014655:Vascular Resistance / Q000187:drug effects
D019332:Endothelin-1; D007166:Immunosuppressive Agents; D011480:Protease Inhibitors; C049331:racecadotril; D016572:Cyclosporine; D009320:Atrial Natriuretic Factor; D015244:Thiorphan; D015260:Neprilysin; D006152:Cyclic GMP