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The Protective Effect of Estrogen Receptor (ER)‐beta Agonist on Cardiac Function Following Trauma‐Hemorrhage: Downregulation of Cardiomyocyte L‐Type Calcium Current (ICa‐L)
Author(s) -
Yang Shaolong,
Zou Luyun,
Hu Shunhua,
Chatham John C.,
Bland Kirby I.,
Machase Richard B.,
Chaudry Irshad H.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1261
Subject(s) - agonist , medicine , cardiac function curve , endocrinology , resuscitation , downregulation and upregulation , selective estrogen receptor modulator , receptor , estrogen receptor , heart failure , anesthesia , chemistry , biochemistry , cancer , breast cancer , gene
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).