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/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.
Pan
Chun-Shui
CS
Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, PR China.
Yang
Jing-Hui
JH
Cai
Da-Yong
DY
Zhao
Jing
J
Gerns
Helen
H
Yang
Jun
J
Chang
Jaw-Kang
JK
Tang
Chao-Shu
CS
Qi
Yong-Fen
YF
D053607:Adrenomedullin; D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D003326:Coronary Circulation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007930:Leucine / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D010477:Perfusion; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016277:Ventricular Function, Left / Q000187:drug effects
C499411:Adm2 protein, rat; D009479:Neuropeptides; D010446:Peptide Fragments; D012333:RNA, Messenger; D053607:Adrenomedullin; D000242:Cyclic AMP; D007930:Leucine