Pan Chun-Shui, Yang Jing-Hui, Cai Da-Yong, Zhao Jing, Gerns Helen, Yang Jun, Chang Jaw-Kang, Tang Chao-Shu, Qi Yong-Fen
Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, PR China.
Peptides. 2005 Sep;26(9):1640-6. doi: 10.1016/j.peptides.2005.02.013. Epub 2005 Mar 16.
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/dt(max)), 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/dt (max), by 33 and 47% (P<0.01); lower -LVdp/dt(max), 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.
肾上腺髓质素（IMD）是降钙素/降钙素基因相关肽（CGRP）家族的一个新成员。本研究旨在探讨IMD的不同片段（IMD1 - 47和IMD8 - 47）对大鼠心血管系统的影响。静脉持续注射150 nmol的IMD片段可使平均动脉压持续下降，并抑制心脏功能。给予IMD片段可降低左心室收缩末期压力（LVESP）和左心室压力上升最大速率（±LVdp/dt(max)），并升高左心室舒张末期压力（LVEDP）。IMD1 - 47治疗引起的变化与IMD8 - 47相近（P>0.05）。在体外，用IMD8 - 47（10(-8)和10(-7)mol/L）灌注离体大鼠心脏，可使左心室收缩压（LVSP）分别降低40%和56%（P<0.01）；使+LVdp/dt (max)分别降低33%和47%（P<0.01）；使 -LVdp/dt(max)分别降低25%和39%（P<0.01）；但使冠状动脉灌注流量（CPF）分别升高25%（P<0.05）和33%（P<0.01）。然而，IMD8 - 47和IMD1 - 47（浓度范围为10(-13)至10(-7)mol/L）均可使预收缩的主动脉环呈剂量依赖性舒张。在体内，静脉注射IMD1 - 47和IMD8 - 47（10(-7)mol/L）后，心肌中环磷酸腺苷（cAMP）含量分别比对照组升高68%和150%（均P<0.01），主动脉中cAMP含量分别比对照组升高320%和281%（均P<0.01）。用IMD1 - 47和IMD8 - 47（10(-7)mol/L）灌注离体心脏，与对照组相比，cAMP含量分别升高24%（P<0.05）和73%（P<0.01）。IMD以浓度依赖性方式抑制心肌细胞中3H - 亮氨酸的掺入。IMD1 - 47和IMD8 - 47（10(-7)和10(-8)mol/L）分别使3H - 亮氨酸掺入量降低12 - 25%（P<0.01）和14 - 18%（P<0.01）。在培养的新生心肌细胞和异丙肾上腺素诱导的肥厚心肌中检测到IMD mRNA，但在成年大鼠的正常心肌中未检测到。这些结果表明，IMD作为一种心血管活性肽，可能是心血管功能和心肌肥大的调节因子。
