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 (NIH grants R37 GM39519 & R01 HL076165‐03).