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Time‐dependent mechanisms of ethanol‐evoked acute hypotensive and cardiac depressant effects in conscious female rats
Author(s) -
Ibrahim Badr Mostafa,
Fan Ming,
AbdelRahman Abdel A
Publication year - 2013
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.27.1_supplement.654.16
Subject(s) - catalase , oxidative stress , malondialdehyde , ethanol , acetaldehyde , chemistry , aldh2 , pharmacology , cardiac function curve , aldehyde dehydrogenase , oxidative phosphorylation , alcohol dehydrogenase , antioxidant , endocrinology , reactive oxygen species , medicine , biochemistry , enzyme , heart failure
The molecular mechanisms for the acute hypotensive and cardiac depressant effects of ethanol in proestrus rats are not known. We tested the hypothesis that exacerbated myocardial oxidative stress contribute to the acute ethanol‐evoked myocardial dysfunction and ultimately the hypotensive response in proestrus female rats. Ethanol (1g/kg) or an equal volume of water (control) was administered via nasogastric tube to 48 proestrous rats (divided to 3 ethanol and 3 water groups; n = 6–8), and hemodynamic measurements continued for 30, 60 or 90 min. To elucidate the role of pro‐oxidant and antioxidant mechanisms in the ethanol‐evoked myocardial dysfunction, the catalytic activities of acetaldehyde (ACA) generating [alcohol dehydrogenase (ADH) and catalase] and eliminating (ALDH2) enzymes were measured in the collected cardiac tissues at the specified time points. Further, we measured the levels of markers of oxidative stress (ROS and Nox activity), myocardial kinases (phosphorylated Akt and ERK1/2), and myocardial levels of: (i) the cardiotoxic aldehyde malondialdehyde (MDA), and (ii) 4‐hydroxy‐2‐nonenal (4‐HNE)‐modified proteins. The ex vivo studies revealed: (i) enhanced (ADH), without a change in ALDH2, activity (indicative of elevated ACA levels), (ii) increases in mediators of oxidative stress such as phosphorylated (p) Akt and pERK1/2, Nox activity enhanced along with ROS, (iii), elevated MDA and 4‐HNE‐modified proteins expression. These molecular responses along with the inhibition of myocardial catalase activity coincided with the drastic reductions in cardiac function and BP at 90 min post‐ethanol. The findings implicate local ethanol/ACA metabolizing enzymes in the myocardial oxidative stress, which along with the accumulation of cardiotoxic aldehydes lead to ethanol‐evoked myocardial dysfunction and hypotension in conscious proestrus female rats. Supported by NIAAA Grant 2R01 AA14441–06