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This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/H409    most recent 01018.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Merkel, M. J. Articles by Van Winkle, D. M. PubMed PubMed Citation Articles by Merkel, M. J. Articles by Van Winkle, D. M.

Estradiol abolishes reduction in cell death by the opioid agonist Met⁵-enkephalin after oxygen glucose deprivation in isolated cardiomyocytes from both sexes

¹Department of Anesthesiology and Peri-Operative Medicine, Oregon Health and Science University; and ²Anesthesiology and ³Research Services, Veterans Affairs Medical Center Oregon, Portland, Oregon

Submitted 4 September 2007 ; accepted in final form 19 May 2008

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.

viability; sex hormone; hypoxia