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

Ischemic heart disease remains the leading cause of morbidityand mortality in aged women, with a 2‐ to 3‐fold increased incidencefollowing menopause. Clinical trials have failed to demonstrate cardioprotectivebenefit from chronic estrogen (E2) replacement therapy, yet protective effects of E2 occur in adult animal models and are in part mediated by non‐genomic estrogen receptor α (ERα) signaling. The role of ERβ is less clear. The purpose of the present study was to determine the efficacy of acute ERβ activation on reducing cardiac ischemia/reperfusion (I/R) injury in aged E2‐deficient female rats. Hearts were isolated from adult (6mo; n=9), aged (24mo; n=13), and aged ovariectomized (OVX; n=14) F344 rats. Hearts were perfused in Langendorff mode and subjected to 47 min of global I and 60 min of R. Rats were acutely treated with the ERβ‐agonist diarylpropionitrile (DPN) 45 min prior to I/R (5μg/kg, s.c.), and mRNA isolated to determine ERβ expression. Here, for the first time, our data suggest that acute treatment with DPN does not affect functional recovery following I/R injury in adult, aged, or aged OVX female rats. Additionally, we were unable to detect ERβ mRNA in the adult or aged female rat myocardium. These data indicate that acute ERβ activation does not impact I/R injury in the female rat heart and bring into question the relevance of non‐genomic ERβ signaling during I/R injury. Funding Source: NIH R01 HL091097