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Estrogen Reduces Cardiac Injury and Expression of β 1 -Adrenoceptor upon Ischemic Insult in the Rat Heart

2004; American Society for Pharmacology and Experimental Therapeutics; Volume: 309; Issue: 1 Linguagem: Inglês

10.1124/jpet.103.058339

1521-0103

Kenneth W L Kam, Jian Song Qi, Mai Chen, Tak Ming Wong,

Cardiac Ischemia and Reperfusion

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 β 1 -AR in sham, ovariectomized (Ovx) and estrogen replaced (Ovx + E 2 ) rats. When β-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 β 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 β 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 β 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 β 1 -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 β 1 -AR in Ovx rats represents a novel cardioprotective mechanism of estrogen replacement therapy.