Several review articles have been published on the neurobehavioral actions of
acetaldehyde and other
ethanol metabolites as well as in major
alcohol-related disorders such as
cancer and liver and
lung disease. However, very few reviews dealt with the role of alcohol metabolism in the adverse cardiac and
autonomic effects of alcohol and their potential underlying mechanisms, particularly in vulnerable populations. In this chapter, following a brief overview of the dose-related favorable and adverse cardiovascular effects of alcohol, we discuss the role of
ethanol metabolism in its adverse effects in the brainstem and heart. Notably, current knowledge dismisses a major role for
acetaldehyde in the adverse autonomic and cardiac effects of alcohol because of its low tissue level in vivo. Contrary to these findings in men and male rodents, women and hypertensive individuals are more sensitive to the adverse cardiac effects of similar amounts of alcohol. To understand this discrepancy, we discuss the autonomic and cardiac effects of alcohol and its metabolite
acetaldehyde in a model of
hypertension, the spontaneously hypertensive rat (SHR) and female rats. We present evidence that enhanced
catalase activity, which contributes to cardioprotection in
hypertension (compensatory) and in the presence of
estrogen (inherent), becomes detrimental due to
catalase catalysis of alcohol metabolism to
acetaldehyde. Noteworthy, studies in SHRs and in
estrogen deprived or replete normotensive rats implicate
acetaldehyde in triggering oxidative stress in autonomic nuclei and the heart via (i) the Akt/
extracellular signal-regulated kinases (ERK)/
nitric oxide synthase (NOS) cascade and (ii)
estrogen receptor-alpha (ERα) mediation of the higher
catalase activity, which generates higher
ethanol-derived
acetaldehyde in female heart. The latter is supported by the ability of ERα blockade or
catalase inhibition to attenuate alcohol-evoked myocardial oxidative stress and dysfunction. More mechanistic studies are needed to further understand the mechanisms of this public health problem.