Effects of intermedin(1-53) on cardiac function and ischemia/reperfusion injury in isolated rat hearts.
Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CT/CGRP) family identified from human and other vertebrate tissues. Preprointermedin (preproIMD) can generate a 47 amino acid mature peptide (IMD(1-47)) and a shorter 40 amino acid one (IMD(8-47)) by proteolytic cleavage. Amino acid sequence analysis showed that cleavage sites are located between two basic amino acids at Arg93-Arg94, resulting in the production of preproIMD(95-147), namely IMD(1-53). The present study was designed to observe the effects of IMD(1-53) on cardiac function in ischemia/reperfusion (I/R) injury in isolated rat hearts. Perfusion with high-dose IMD(1-53) gave higher left ventricular systolic pressure (LVSP) and maximal rate of increase and decrease of left ventricle pressure (+/-LVdP/dt(max)), and coronary perfusion flow (CPF) than those of controls. Cardiac I/R induced a marked inhibition of cardiac function and myocardial injury. Reperfusion with IMD(1-53) significantly ameliorated the inhibited cardiac function and bradycardia induced by I/R. Compared with the I/R-treatment alone, IMD(1-53) reperfusion augmented CPF, LVSP, and maximal rate of increase and decrease of left ventricle pressure (+/-LVdP/dt(max)) and decreased LVDP. In addition, reperfusion with IMD(1-53)markedly attenuated the leakage of lactate dehydrogenase and malondialdehyde content in myocardia compared with I/R alone. Reperfusion with IMD(1-53)increased the content of cyclic adenosine monophosphate in comparison with I/R alone. Interestingly, the above IMD(1-53) effects are similar to those of adrenomedullin. These results suggest that IMD(1-53), like adrenomedullin, has cardioprotective effects against myocardial I/R injury.
Yang
Jing-Hui
JH
Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China.
Jia
Yue-Xia
YX
Pan
Chun-Shui
CS
Zhao
Jing
J
Ouyang
Ming
M
Yang
Jun
J
Chang
Jaw-Kang
JK
Tang
Chao-Shu
CS
Qi
Yong-Fen
YF
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D016277:Ventricular Function, Left / Q000187:drug effects
D009074:Melanocyte-Stimulating Hormones; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide