Estrogen Receptor Beta Does Not Influence Ischemic Tolerance in the Aged Female Rat Heart

Introduction: Ischemic heart disease remains the leading cause of morbidity and mortality in aged women, with a 2‐ to 3‐fold increase in incidence following menopause. Clinical trials have failed to demonstrate cardioprotective benefit from chronic estrogen (E₂) replacement therapy, yet protective effects of E₂ have been demonstrated in adult animal models and are mediated by the estrogen receptor (ER) subtypes ERα and ERβ. Aims: The aim of this study was to determine the effects of acute ERβ activation on ischemia/reperfusion (I/R) injury in adult, aged, and aged E₂‐deficient female rats. Methods: Hearts were isolated from adult (6 months; n = 9), aged (24 months; n = 13), and aged ovariectomized (OVX; n = 14) female Fischer 344 rats and subjected to 47 min of global I and 60 min of R. Rats were acutely treated with the ERβ‐agonist diarylpropionitrile (DPN; 5μg/kg) or vehicle 45 min prior to I/R; ERβ mRNA and protein levels were also assessed. Results: Acute treatment with DPN had no effect on functional recovery following I/R injury in adult, aged, or aged OVX female rats. Additionally, we were unable to detect ERβ mRNA or protein in the adult or aged female rat myocardium. Conclusions: Here, for the first time, our data suggest that acute ERβ activation does not impact ischemic tolerance in the adult or aged female Fischer 344 rat myocardium and this likely due to a lack of detectable ERβ.