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Aldehyde Dehydrogenase Inhibition Ameliorates Cardiac Dysfunction and Exacerbates Hypotension Caused by Alcohol in Female Rats
Author(s) -
Yao Fanrong,
AbdelRahman Abdel A.
Publication year - 2020
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.14225
Subject(s) - cyanamide , aldh2 , oxidative stress , aldehyde dehydrogenase , endocrinology , medicine , alcohol dehydrogenase , malondialdehyde , alcohol , catalase , chemistry , ethanol , pharmacology , biochemistry , enzyme
Background Aldehyde dehydrogenase 2 (ALDH2) protects against alcohol‐evoked cardiac dysfunction in male rodents, but its role in the estrogen (E 2 )‐dependent hypersensitivity of female rats to alcohol‐evoked myocardial oxidative stress and dysfunction is not known. Methods We addressed this question by studying the effect of cyanamide (ALDH2 inhibitor) on cardiac function, blood pressure, alcohol‐metabolizing enzyme (alcohol dehydrogenase, cytochrome P450 2E1, catalase, and ALDH2) activities, and cardiac redox status (reactive oxygen species, ROS; malondialdehyde, MDA) in the absence or presence of ethanol (EtOH) in female sham‐operated (SO) and ovariectomized (OVX) rats. Results Cyanamide attenuated the EtOH‐evoked myocardial dysfunction (reduced d P /d t max and LVDP) in SO rats. EtOH, cyanamide, or their combination did not alter d P /d t max or LVDP in OVX rats. Cyanamide induced cardiac oxidative stress and abrogated the subsequent alcohol‐evoked increases in ROS and MDA levels in SO rats. Neither EtOH nor cyanamide influenced ROS or MDA levels in OVX rats. Importantly, cyanamide exaggerated EtOH‐evoked hypotension in SO and uncovered this hypotensive response in OVX rats, which implicates ALDH2 in the vasodilating effect of EtOH. Conclusions Contrary to our hypothesis, cyanamide attenuated the E 2 ‐dependent cardiac dysfunction caused by alcohol, likely by preconditioning the heart to oxidative stress, while exacerbating the vasodilating effect of alcohol. The latter might predispose to syncope when cyanamide and alcohol are combined in females.