McDowell G, Coutie W, Shaw C, Buchanan K D, Struthers A D, Nicholls D P
Department of Medicine, Royal Victoria Hospital, Belfast.
Br J Clin Pharmacol. 1997 Mar;43(3):329-32. doi: 10.1046/j.1365-2125.1997.00545.x.
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.
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.
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.
We conclude that neutral endopeptidase inhibition increases circulating plasma levels of ET and CGRP in addition to the natriuretic peptides.
坎多沙坦酯是一种特异性中性内肽酶（NEP）24.11抑制剂，先前的研究已证明NEP抑制对心房利钠肽和脑利钠肽（ANP、BNP）的作用。本研究的目的是确定NEP抑制对血管活性肽循环水平的影响。
我们研究了7例慢性心力衰竭患者，他们被随机分配以四交叉、双盲模式接受坎多沙坦酯、坎多沙坦酯/卡托普利、卡托普利和安慰剂治疗。
安慰剂治疗2小时后，内皮素（ET）的平均循环水平升高（从10至20 pg/ml），降钙素基因相关肽（CGRP）的平均循环水平也升高（从27至51 pg/ml），但在此期间ANP水平变化不大（从73至75 pg/ml）。然而，服用坎多沙坦酯后，ET（从10至39 pg/ml，P<0.05）、CGRP（从34至99 pg/ml，P<0.05）和ANP（从72至108 pg/ml，P<0.05）进一步升高。坎多沙坦酯与卡托普利联合治疗后观察到类似结果。
我们得出结论，中性内肽酶抑制除了增加利钠肽外，还会增加ET和CGRP的循环血浆水平。
