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The protective effects of 17beta-estradiol against ischemia–reperfusion injury and its effect on pacing postconditioning protection to the heart

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Abstract

The role of pacing postconditioning (PPC) in the heart protection against ischemia–reperfusion injury is not completely understood. The aim of this study was to investigated if 17-β-estradiol (estrogen, E2), endogenous atrial natriuretic peptide (ANP), endogenous brain natriuretic peptide (BNP), and tumor necrosis factor-alpha (TNF-α) are involved in PPC-mediated protection. Langendorff perfused female Wistar rat hearts were used for this study. Hearts challenged with regional ischemia for 30 min subjected to no further treatment served as a control. The PPC protocol was 3 cycles of 30 s pacing alternated between the right atrium and left ventricle (LV). Protection was assessed by recovery of LV contractility and coronary vascular–hemodynamics. Ischemia induced a significant (P < 0.05) deterioration in the heart function compared with baseline data. PPC alone or in combination with short-term E2 treatment (E2 infusion at the beginning of reperfusion) significantly (P < 0.05) improved the heart functions. Short-term E2 treatment post-ischemically afforded protection similar to that of PPC. However, long-term E2 substitution for 6 weeks completely attenuated the protective effects of PPC. Although no changes were noted in endogenous ANP levels, PPC significantly increased BNP expression level and decreased TNF-α in the cardiomyocyte lysate and coronary effluent compared to ischemia and controls. Our data suggested a protective role for short-term E2 treatment similar to that of PPC mediated by a pathway recruiting BNP and downregulating TNF-α. Our study further suggested a bad influence for long-term E2 substitution on the heart as it completely abrogated the protective effects of PPC.

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Acknowledgments

This study was supported by grant # MY 03/10 from Kuwait University. We also acknowledge the research core facility Kuwait University grant # GM 01/01. We thank Professor Frits W. Prinzen (Department of Physiology, Maastricht University, the Netherlands) for his invaluable comments on the manuscript.

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The authors have nothing to disclose.

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Correspondence to Fawzi A. Babiker.

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Babiker, F.A., Joseph, S. & Juggi, J. The protective effects of 17beta-estradiol against ischemia–reperfusion injury and its effect on pacing postconditioning protection to the heart. J Physiol Biochem 70, 151–162 (2014). https://doi.org/10.1007/s13105-013-0289-9

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  • DOI: https://doi.org/10.1007/s13105-013-0289-9

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