17β-estradiol decreases vulnerability to ventricular arrhythmias by preserving Connexin43 protein in infarcted rats

Chien Chang Chen, Chih Chan Lin, Tsung-Ming Lee

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21 Citations (Scopus)

Abstract

Epidemiological studies showed that a lower mortality rate of sudden cardiac death among women than among men may depend on the action of female sex hormones. This study assessed whether 17β-estradiol exerts anti-arrhythmic effects through enhanced Connexin43 (Cx43) expression after infarction. Two weeks after ovariectomy, female Wistar rats were randomly assigned to coronary artery ligation or sham-operation. Twenty-four hours after coronary ligation, ovariectomized rats were randomized into vehicle, subcutaneous estradiol treatment, tamoxifen, or subcutaneous estradiol treatment + tamoxifen and followed for 4 weeks. To verify the role of estradiol-related nitric oxide in modulating the expression of Cx43, N-nitro-L-arginine methyl ester was also assessed in an in vitro study. Myocardial Cx43 expression revealed a significant decrease in vehicle-treated infarcted rats compared with sham-operated rats at 24 h and 4 weeks after infarction. Attenuated Cx43 expression was blunted after administering estradiol, assessed by immunofluorescent analysis, Western blotting, and real-time quantitative RT-PCR of Cx43. The vulnerability for ventricular arrhythmia during programmed stimulation in estradiol-treated infarcted rats was significantly lower than in vehicle-treated infarcted rats. The beneficial effect of estradiol on Cx43 was abolished by tamoxifen. In addition, the in vitro study demonstrated that the amount of Cx43 showed significant reduction after adding N-nitro-L-arginine methyl ester. Chronic administration of estradiol after infarction is associated with attenuated reduction of gap junction proteins probably through a nitric oxide-dependent pathway via the estrogen receptor and thus plays a critical role in the beneficial effect on arrhythmic vulnerability response to programmed electrical stimulation.

Original languageEnglish
Pages (from-to)73-81
Number of pages9
JournalEuropean Journal of Pharmacology
Volume629
Issue number1-3
DOIs
Publication statusPublished - Mar 10 2010

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Keywords

  • Arrhythmias
  • Connexin43
  • Echocardiogram
  • Estradiol
  • Myocardial infarction

ASJC Scopus subject areas

  • Pharmacology

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