The effect of the neutral endopeptidase inhibitor drug, candoxatril, on circulating levels of two of the most potent vasoactive peptides.
OBJECTIVE
Candoxatril is a specific neutral endopeptidase (NEP) 24.11 inhibitor, and previous work has documented the effect of NEP inhibition on atrial and brain natriuretic peptides (ANP, BNP). The aim of the present study was to ascertain the effect of NEP inhibition on circulating levels of vasoactive peptides.


METHODS
We studied seven patients with chronic heart failure who were randomized to receive candoxatril, candoxatril/captopril, captopril and placebo in a four way cross over, double-blind pattern.


RESULTS
The mean circulating level of endothelin (ET) was increased 2 h after placebo (10 to 20 pg ml-1) and also calcitonin gene-related peptide (CGRP) (27 to 51 pg ml-1), but ANP levels changed little during this time (73 to 75 pg ml-1). Following candoxatril, however, ET (10 to 39 pg ml-1, P < 0.05), CGRP (34 to 99 pg ml-1, P < 0.05) and ANP (72 to 108 pg ml-1, P < 0.05) increased further. A similar result was observed following combined treatment with candoxatril and captopril.


CONCLUSIONS
We conclude that neutral endopeptidase inhibition increases circulating plasma levels of ET and CGRP in addition to the natriuretic peptides.
McDowell
G
G
Department of Medicine, Royal Victoria Hospital, Belfast.
Coutie
W
W
Shaw
C
C
Buchanan
K D
KD
Struthers
A D
AD
Nicholls
D P
DP
D000368:Aged; D000704:Analysis of Variance; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D016232:Endothelins / Q000097:blood; D006333:Heart Failure / Q000097:blood* / Q000201:enzymology; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D008297:Male; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000097:blood*; D011355:Prodrugs / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*
D016232:Endothelins; D007189:Indans; D009419:Nerve Tissue Proteins; D011355:Prodrugs; D011422:Propionates; D011480:Protease Inhibitors; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; C062766:candoxatril; D015740:Calcitonin Gene-Related Peptide