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Enhanced oxidative stress/DAPK3/Akt/ERK signaling accounts for estrogen exacerbation of cardiac dysfunction caused by ethanol in male rats (652.20)
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.652.20
Subject(s) - oxidative stress , malondialdehyde , endocrinology , medicine , protein kinase b , blood pressure , ovariectomized rat , chemistry , reactive oxygen species , lipid peroxidation , cardiac function curve , pharmacology , estrogen , phosphorylation , heart failure , biochemistry
We have previously shown that acute ethanol reduces blood pressure (BP) and cardiac output in female, but not in male, rats. Because these effects of ethanol were estrogen (E 2 )‐dependent, we investigated whether E 2 treatment of male rats uncovers a hypotensive effect for ethanol, and whether left ventricular (LV) dysfunction, due to oxidative damage, contributes to the ethanol‐E 2 hemodynamic interaction. The effect of ethanol (0.5, 1 or 1.5 g/kg; i.v.) on BP, LV function, and oxidative stress markers in male rats treated with E 2 (1 μg/kg i.v.) or the vehicle were investigated. While ethanol had no effect on BP in vehicle‐treated rats, it caused dose‐related falls in BP in E 2 ‐pretreated rats. This was associated with (i) compromised myocardial function as suggested by the reductions in LV developed pressure (LVDP), end diastolic pressure (LVEDP), and rate of rise in LV pressure (LV dP/dt max ), and (ii) oxidative damage as evidenced by the increases in LV generation of reactive oxygen species, protein expression of the malondialdehyde adducts, and phosphorylated death‐associated protein kinase‐3 (DAPK3), Akt, and ERK1/2. Together, E 2 propagates LV dysfunction and hypotension in response to ethanol in male rats via facilitation of the myocardial oxidative stress/lipid peroxidation/DAPK3/Akt/ERK1/2 cascade. Because E 2 was administered acutely, its effects are likely to involve rapid nongenomic mechanisms.Grant Funding Source : Supported by NIAAA [2R01 AA014441‐07].