Mechanism of cardioprotection following trauma-hemorrhagic shock by a selective estrogen receptor-β agonist: up-regulation of cardiac heat shock factor-1 and heat shock proteins

Abstract

Although 17β-estradiol (E2) administration following trauma-hemorrhage (T-H) improves cardiac function in male rodents, it is not known whether the salutary effects of E2 are mediated via estrogen receptor (ER)-α or ER-β, and whether cardiac heat shock proteins (Hsp) are affected by E2 administration. Male Sprague–Dawley rats underwent T-H (mean BP 40 mmHg for 90 min, then resuscitation). ER-α agonist propyl pyrazole triol (PPT) (5 μg/kg), ER-β agonist diarylpropiolnitrile (DPN) (5 μg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. At 24 h after T-H or sham operation, cardiac output (CO), stroke volume (SV), mean blood pressure, and ± dP/dt max were measured (n = 6 rats per group). Cardiac Hsp32, 60, 70, and 90 mRNA/protein expressions and heat shock factor (HSF)-1 DNA binding activity were determined. One-way ANOVA and Tukey's test were used for statistical analysis. CO, SV and ± dP/dt max decreased significantly after T-H, however, administration of ER-β agonist DPN after T-H restored the above parameters. Moreover, DPN treatment prevented T-H-mediated decrease in Hsp60 mRNA/protein and Hsp90 protein expressions in the heart. Hsp32 and Hsp70 mRNA/protein expression and HSF-1 DNA binding activity in the hearts were increased even above the shams in DPN treated T-H rats. In contrast, no significant change in the above parameters was observed in T-H rats treated with ER-α agonist PPT. Thus, the salutary effects of E2 on cardiac function are mediated via ER-β and ER-β-induced up-regulation of Hsp likely plays a significant role in the E2-mediated cardioprotection after T-H.