Apelin protects myocardial injury induced by isoproterenol in rats.
We aimed to explore the change in level of apelin and its receptor APJ during myocardial injury and the therapeutic effects of apelin in myocardial injury. Rat myocardial injury was induced by subcutaneous injection of a high dose of isoproterenol (ISO); apelin and APJ mRNA levels were determined by RT-PCR; APJ protein was determined by Western blot; EIA and RIA were used to measure the apelin content and receptor binding, respectively. Plasma lactate dehydrogenase (LDH) activity and myocardial and plasma malondialdehyde (MDA) contents were higher in ISO-treated hearts than that in controls. ISO-treated rats showed lower +/-LV dp/dt(max) values and higher LVEDP value (all P<0.01), which suggested severe heart failure. As well, the apelin content in plasma, atrial and ventricular myocardium was decreased by 27%, 30% and 25% (P<0.01), respectively. The mRNA levels of apelin and APJ in myocardia were also markedly reduced; but the APJ protein level in myocardia was increased. However, administration of apelin significantly ameliorated myocardial injury and ISO-induced heart failure. Compared with the ISO-alone group, the group given low-dosage apelin (5 nmol/kg/day) had 39% and 66% higher +LV dp/dt(max) and -LV dp/dt(max) values, and 40.7% lower LVEDP value (P<0.01), and the leakage of myocardial LDH and increased MDA content were attenuated (all P<0.01). Interestingly, bolus injections of apelin (10 nmol/kg/day) resulted in potent inotropic effects in ISO-treated rats. ISO-induced myocardial injury resulted in hypoexpression of apelin and its receptor APJ, and the administration of exogenous apelin ameliorated heart failure and myocardial injury. Apelin could have a cardioprotective effect, and the apelin-APJ system may be a new therapeutic target in myocardial injury and heart failure.
Jia
Yue-Xia
YX
Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China.
Pan
Chun-Shui
CS
Zhang
Jing
J
Geng
Bin
B
Zhao
Jing
J
Gerns
Helen
H
Yang
Jun
J
Chang
Jaw-Kang
JK
Tang
Chao-Shu
CS
Qi
Yong-Fen
YF
D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins; D007545:Isoproterenol / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
D000073861:Apelin; D000075244:Apelin Receptors; C498579:Apln protein, rat; C491284:Aplnr protein, rat; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D007545:Isoproterenol