Effect of relaxin on myocardial ischemia injury induced by isoproterenol.
The omnipresent 6-kDa polypeptide relaxin (RLX) is emerging as a multifunctional endocrine and paracrine factor in a broad range of target tissues including cardiovascular tissues. To explore the pathophysiological roles of RLX in ischemic cardiovascular diseases, we studied the changes in RLX mRNA level in the myocardium and the effect of RLX supplements in rats with isoproterenol (ISO)-induced myocardial injury. In ISO-treated rats, RLX levels in myocardia and plasma increased 3.7- and 6.9-fold, respectively (P<0.01), the mRNA level increased significantly in myocardia compared with controls. Co-administration of RLX (0.2 and 2.0 microg/kg/d) and ISO increased left-ventricular pressure development and decreased left ventricular end-diastolic pressure (LVDEP) (all P<0.01). Malondialdehyde content in myocardia and lactate dehydrogenase and creatine phosphokinase activities in plasma in RLX-treated rats decreased markedly compared with that in ISO-treated alone rats (P<0.01 or P<0.05). In the high-dose RLX group, fibroblastic hyperplasia was relieved in myocardia, hydroxyproline level was lower, by 33% (P<0.05), and endothelin content in plasma was lower, by 31% (P<0.01) than in the ISO-alone group. Compared with control group, any indexes in sham rats treated with high-dose RLX were unaltered (all P>0.05). These results showed an up-regulation of myocardial RLX during ISO-induced myocardial ischemia injury and the protective effect of RLX on ISO-induced cardiac inhibition and fibrosis, which suggests that RLX could be an endogenous cardioprotective factor in ischemic heart diseases.
Zhang
Jing
J
Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China.
Qi
Yong-Fen
YF
Geng
Bin
B
Pan
Chun-Shui
CS
Zhao
Jing
J
Chen
Li
L
Yang
Jun
J
Chang
Jaw-Kang
JK
Tang
Chao-Shu
CS
D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000473:pathology; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D016232:Endothelins / Q000097:blood; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012065:Relaxin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D016232:Endothelins; D009419:Nerve Tissue Proteins; C466742:RLN3 protein, rat; D012333:RNA, Messenger; D012065:Relaxin; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D007545:Isoproterenol; D006909:Hydroxyproline