Premium
Nongenomic effects of estrogen mediate the dose‐related myocardial oxidative stress and dysfunction caused by acute ethanol in female rats (652.19)
Author(s) -
ElMas Mahmoud,
AbdelRahman Abdel
Publication year - 2014
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.28.1_supplement.652.19
Subject(s) - ovariectomized rat , oxidative stress , endocrinology , medicine , malondialdehyde , estrogen , estrogen receptor , chemistry , ethanol , protein kinase b , reactive oxygen species , catalase , phosphorylation , biochemistry , cancer , breast cancer
Acute ethanol lowers blood pressure (BP) and cardiac output in proestrus and after chronic estrogen (E 2 ) replacement in ovariectomized (OVX) female rats. However, whether rapid nongenomic effects of E 2 mediate these hemodynamic effects of ethanol remained unanswered. To test this hypothesis, we investigated the effect of ethanol (0.5, 1 or 1.5 g/kg; i.v.) on left ventricular (LV) function and oxidative markers in OVX rats pretreated 30 min earlier with 1 μg/kg E 2 (OVXE 2 ) or vehicle (OVX) and in proestrus sham‐operated (SO) rats. In SO rats, ethanol caused significant and dose‐ related reductions in BP, rate of rise in LV pressure (LV dP/dt max ), and LV developed pressure (LVDP). The ethanol effects disappeared in OVX rats and were restored in OVXE 2 rats suggesting rapid estrogen receptor signaling mediates the detrimental LV effects of ethanol. The E 2 ‐dependent LV dysfunction caused by ethanol was associated with higher LV: (i) generation of reactive oxygen species, (ii) expression of the malondialdehyde and 4‐hydroxynonenal protein adducts, (iii) Akt and ERK1/2, and (iv) catalase activity. Collectively, it is concluded that rapid estrogen receptor signaling is implicated in the cellular events that lead to the generation of aldehyde protein adducts and Akt/ERK1/2 phosphorylation, which ultimately mediate the estrogen‐dependent LV oxidative stress and dysfunction caused by ethanol in female rats.Grant Funding Source : Supported by NIAAA [2R01 AA014441‐07]