Calcitonin gene-related peptide is not elevated in rat plasma by heart failure or by neutral endopeptidase inhibition

Abstract

Some studies have indicated that plasma calcitonin gene-related peptide (CGRP) increases in congestive heart failure (CHF). In vitro, neutral endopeptidase (NEP) cleaves CGRP. We studied CGRP-like immunoreactivity (CGRP-ir) in rat plasma in a coronary artery-ligation model of CHF with and without NEP inhibition. Rats with CHF (n=6) and shamoperated 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 (SAP) was measured while conscious. All rats were killed by exsanguination, and heart and lungs were removed and weighed. In CHF rats, plasma atrial natriuretic peptide after vehicle (basal ANP) was 7.6- fold, but basal CGRP-ir was similar compared to controls. After SCH 34826, plasma CGRP-ir decreased marginally in CHF rats (57->51 ng/l, p=0.011), and 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 relative 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 rats, plasma CGRP-ir did not correlate with HE, LU, SAP, plasma ANP or PRA, 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 either by NEP inhibition, or in post-infarction CHF.