Estradiol abolishes reduction in cell death by the opioid agonist Met 5-enkephalin after oxygen glucose deprivation in isolated cardiomyocytes from both sexes

Matthias J. Merkel, Lijuan Liu, Zhiping Cao, William Packwood, Patricia D. Hurn, Donna M. Van Winkle

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

There is evidence for differences in the response to the treatment of cardiovascular disease in men and women. In addition, there are conflicting results regarding the effectiveness of pharmacologically induced protection or ischemic preconditioning in females. We investigated whether the ability of Met5-enkephalin (ME) to reduce cell death after oxygen-glucose deprivation (OGD) is influenced by the presence of 17β-estradiol (E2) in a nitric oxide (NO)- and estrogen receptor-dependent manner. On postnatal day 7 to 8, murine cardiomyocytes from wild-type or inducible NO synthase (iNOS) knockout mice were separated by sex, isolated by collagenase digestion, cultured for 24 h, and subjected to 90 min OGD and 180 min reoxygenation at 37°C (n = 4 to 5 replicates). Cell cultures were incubated in E2 for 15 min or 24 h before OGD. ME was used to increase cell survival. Cell death was assessed by propidium iodide. More than 300 cells were examined for each treatment. Data are presented as means ± SE. As a result, in both sexes, ME-induced cell survival was lost in the presence of E2, and the ability of ME to improve cell survival was restored after treatment with the estrogen receptor antagonist ICI-182780. Furthermore, iNOS was necessary for ME to increase cell survival following OGD in vitro. We conclude that ME-induced reduction in cell death is abolished by E2 in a sex-independent manner via activation of estrogen receptors, and this interaction is dependent on iNOS.

Original languageEnglish (US)
Pages (from-to)H409-H415
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume295
Issue number1
DOIs
StatePublished - Jul 1 2008

Keywords

  • Hypoxia
  • Sex hormone
  • Viability

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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