K. Helin et al., CALCITONIN-GENE-RELATED PEPTIDE IS NOT ELEVATED IN RAT PLASMA BY HEART-FAILURE OR BY NEUTRAL ENDOPEPTIDASE INHIBITION, Life sciences, 55(6), 1994, pp. 471-477
Citations number
37
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Pharmacology & Pharmacy
Some studies have indicated that plasma calcitonin gene-related peptid
e (CGRP) increases in congestive heart failure (CHF). In vitro, neutra
l endopeptidase (NEP) cleaves CGRP. We studied CGRP-like immunoreactiv
ity (CGRP-ir) in rat plasma in a coronary artery-ligation model of CHF
with and without NEP inhibition. Rats with CHF (n=6) and sham-operate
d controls (n=6) were administered vehicle and, separately, SCH 34826,
a NEP inhibitor, subcutaneously 90 mg/kg. Plasma sample was taken 60
minutes later. Seventeen untreated coronary-ligated rats with various
degrees of CHF were studied separately. Systolic arterial pressure (SA
P) was measured while conscious. All rats were killed by exsanguinatio
n, and heart and lungs were removed and weighed. In CHF rats, plasma a
trial natriuretic peptide after vehicle (basal ANP) was 7.6-fold, but
basal CGRP-ir was similar compared to controls. After SCH 34826, plasm
a CGRP-ir decreased marginally in CHF rats (57-->51 ng/l, p=0.011), an
d ANP increased 1.8-fold (418-->730 ng/l, p=0.001). In controls, these
changes by SCH 34826 were small. Basal ANP correlated strongly with r
elative weight of heart (HE; R=0.93, p<0.001) and lungs (LU; R=0.96, p
<0.001). There was no correlation between basal CGRP-ir, basal plasma
renin activity (PRA), HE and LU. In the untreated coronary-ligated rat
s, plasma CGRP-ir did not correlate with HE, LU, SAP, plasma ANP or PR
A, but plasma ANP correlated with HE (R=0.62, p=0.011) and LU (R=0.70,
p=0.002). We conclude that, in rat plasma, CGRP-ir is not elevated ei
ther by NEP inhibition, or in post-infarction CHF.