Estrogen Reduces Cardiac Injury and Expression of β1-Adrenoceptor upon Ischemic Insult in the Rat Heart

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Abstract
To test the hypothesis that estrogen confers cardioprotection by suppressing the expression of β-adrenoceptor (β-AR), we first correlated the infarct size in response to ischemic insult and β-AR stimulation with the expression of β1-AR in sham, ovariectomized (Ovx) and estrogen replaced (Ovx + E2) rats. When β-AR is being activated during ischemia, the infarct size was significantly greater in Ovx than in the sham and Ovx + E2 rats. There is a negative correlation between the infarct size and the expression level of β1-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 β1-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 β1–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 β1-AR in the Ovx rats, which in turn reduces cardiac injury when β-AR is activated by sympathetic hyperactivity during ischemia. Therefore, suppression of the enhanced expression of cardiac β1-AR in Ovx rats represents a novel cardioprotective mechanism of estrogen replacement therapy.