Nongenomic effects of estrogen mediate the dose‐related myocardial oxidative stress and dysfunction caused by acute ethanol in female rats (652.19)

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]