Cardiovascular effects of newly discovered peptide intermedin/adrenomedullin 2

Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CGRP). The present study aimed to investigate the cardiovascular effects of IMDs (IMD1-47 and IMD8-47) in rats. Intravenous administration of 150 nmol IMDs continuously decreased mean arterial pressure and inhibited cardiac function. Administration with IMDs decreased left ventricular end-systolic pressure (LVESP) and maximal rate of left-ventricle pressure development (±LVdp/dtmax), and elevated left ventricular end-diastolic pressure (LVEDP). Changes with IMD1-47 treatment were close to that with IMD8-47 (P > 0.05). Perfusion of isolated rat hearts in vitro with IMD8-47 (10−8 and 10−7 mol/L) resulted in lower LVSP, by 40 and 56% (P < 0.01); lower +LVdp/dtmax, by 33 and 47% (P < 0.01); lower −LVdp/dtmax, by 25 and 39% (P < 0.01); but higher coronary perfusion flow (CPF), by 25% (P < 0.05) and 33% (P < 0.01), respectively, than controls. However, both IMD8-47 and IMD1-47 (from 10−13 to 10−7 mol/L) relaxed preconstricted aortic rings in a dose-dependent manner. Intravenous administration of IMD1-47 and IMD8-47 (10−7 mol/L) in vivo increased the cyclic adenosine monophosphate (cAMP) content by 68 and 150% (both P < 0.01), respectively, in myocardia and 320 and 281% (both P < 0.01), respectively, in aortas, compared with controls. Perfusion of isolated hearts with IMD1-47 and IMD8-47 (10−7 mol/L) enhanced cAMP content by 24% (P < 0.05) and 73% (P < 0.01), respectively, compared with controls. IMDs inhibited 3H-Leucine incorporation in cardiomyocytes in a concentration-dependent manner. IMD1-47 and IMD8-47 (10−7 and 10−8 mol/L) decreased 3H-Leucine incorporation by 12-25% (P < 0.01) and 14-18% (P < 0.01), respectively. IMD mRNA was detected in cultured neonatal cardiomyocytes and isoproterenol-induced hypertrophic myocardia but not normal myocardia of adult rats. These results suggest that IMD might be a regulatory factor for cardiovascular function and myocardial hypertrophy as a cardiovascular active peptide.