Protective effects of intermedin/adrenomedullin2 on 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 can generate a 47-amino acid mature peptide (IMD(1-47)) and a shorter 40-amino acid one (IMD(8-47)) by proteolytic cleavage. The present study was designed to determine the protective effect of IMD on cardiac ischemia/reperfusion (I/R) injury and its possible mechanism. Isolated rat hearts were perfused on a Langendorff apparatus and subjected to 45-min global ischemia and 30-min reperfusion. Cardiac function was measured. The release of myocardial protein and lactate dehydrogenase (LDH) and the formation of malondialdehyde (MDA) were assayed. Myocardial cAMP content was determined by radioimmunoassay (RIA). Cardiac I/R induced a marked inhibition of cardiac function and myocardial injury. Reperfusion with IMD significantly attenuated the I/R injury. Compared with I/R alone, perfusion with 10(-8)mol/L IMD(1-47) and IMD(8-47) induced a 36% and 33% increase in Delta left ventricular pressure (DeltaLVP), 30% and 28% in maximal rate of increase of LV pressure (+LVdP/dt max), and 34% and 31% in maximal rate of decrease of LV pressure (-LVdP/dt max), respectively (all P<0.01) but an approximately 58% and 51% decrease in LV diastolic pressure, respectively (P<0.01). In addition, perfusion with IMD markedly attenuated the leakage of LDH, total protein and myoglobin from myocardia compared with I/R alone. The contents of ventricular myocardia cAMP after reperfusion with 10(-8)mol/L IMD(1-47) and IMD(8-47) were 130% and 91% higher, respectively, than that with I/R alone (all P<0.01). However, formations of myocardial MDA were 52% and 50% lower than that with I/R alone (all P<0.01), respectively. Interestingly, the above IMD effects were similar to those of adrenomedullin (10(-8)mol/L). These results suggest that IMD, like adrenomedullin, exerts cardio-protective effects against myocardial I/R injury.
Yang
Jing-Hui
JH
Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China.
Qi
Yong-Fen
YF
Jia
Yue-Xia
YX
Pan
Chun-Shui
CS
Zhao
Jing
J
Yang
Jun
J
Chang
Jaw-Kang
JK
Tang
Chao-Shu
CS
D053607:Adrenomedullin; D000818:Animals; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017202:Myocardial Ischemia / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010477:Perfusion; D011312:Pressure; D011485:Protein Binding; D011863:Radioimmunoassay; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy*; D013997:Time Factors
C499411:Adm2 protein, rat; D009479:Neuropeptides; D010455:Peptides; D053607:Adrenomedullin; D000242:Cyclic AMP; D007770:L-Lactate Dehydrogenase