Estrogen reduces cardiac injury and expression of beta1-adrenoceptor upon ischemic insult in the rat heart.
To test the hypothesis that estrogen confers cardioprotection by suppressing the expression of beta-adrenoceptor (beta-AR), we first correlated the infarct size in response to ischemic insult and beta-AR stimulation with the expression of beta(1)-AR in sham, ovariectomized (Ovx) and estrogen replaced (Ovx + E(2)) rats. When beta-AR is being activated during ischemia, the infarct size was significantly greater in Ovx than in the sham and Ovx + E(2) rats. There is a negative correlation between the infarct size and the expression level of beta(1)-AR as revealed by Western blotting and supported by binding analysis. Incubation of ventricular myocytes from Ovx rats with estrogen at 10(-9) M for 24 and 48 h, but not 12 h, significantly reduced lactate dehydrogenase release when the myocytes are subjected to simulated ischemia. The cardioprotective effect of 24 h estrogen incubation was accompanied by a reduction in the protein expression level of beta(1)-AR, which is estrogen receptor-dependent, whereas the lack of protection of 12-h estrogen incubation was not accompanied by any alterations in the expression level of beta(1)-AR. Together, the result from present study suggested that it is most likely that the cardioprotective effect of long-term estrogen replacement is due to suppressing the enhanced expression of cardiac beta(1)-AR in the Ovx rats, which in turn reduces cardiac injury when beta-AR is activated by sympathetic hyperactivity during ischemia. Therefore, suppression of the enhanced expression of cardiac beta(1)-AR in Ovx rats represents a novel cardioprotective mechanism of estrogen replacement therapy.
Kam
Kenneth W L
KW
Department of Physiology, Faculty of Medicine, The University of Hong Kong Special Administrative Region, China.
Qi
Jian Song
JS
Chen
Mai
M
Wong
Tak Ming
TM
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004958:Estradiol / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D017202:Myocardial Ischemia / Q000150:complications* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*
D004967:Estrogens; D018342:Receptors, Adrenergic, beta-1; D004958:Estradiol; D000242:Cyclic AMP