The Protective Effect of Estrogen Receptor (ER)-beta Agonist on Cardiac Function Following Trauma-Hemorrhage: Downregulation of Cardiomyocyte L-Type Calcium Current (ICa-L).

Although 17β-estradiol (E2) administration after trauma-hemorrhage (T-H) produces salutary effects on cardiac function, the precise mechanism remains unknown. Additional studies have shown that cardiomyocyte I_ca-L increased after T-H and the protective effect of E2 on cardiac function correlated with the attenuation of cardiomyocyte I_ca-L. Although E2 produces various salutary effects, it is not known whether ER-α agonist (PPT) or β agonist (DPN) also attenuates cardiomyocyte I_ca-L. Male rats (250-275 g) underwent T-H (removal of 60% of the circulating blood and fluid resuscitation after 90 min of hypotension) and received PPT, DPN (10 µg/kg, IV) or Cyclodextrin (20.7 mg/kg, IV, control) during resuscitation. Left ventricular (LV) performance was measured at 24 h and cardiomyocytes were then isolated. The whole-cell patch-clamp technique was employed to measure cardiomyocyte I_ca-L. The results indicated that LV performance was decreased and cardiomyocyte I_ca-L increased significantly after T-H; however, DPN restored cardiac function and attenuated the increase of cardiomyocyte I_ca-L. In contrast, the beneficial effects of PPT on cardiac function did not reach a significance level. Thus, the salutary effect of E2 following trauma-hemorrhage appears to be primarily mediated via the ER-β receptor and may be a consequence of attenuation of cardiomyocyte I_ca-L [ABSTRACT FROM AUTHOR]