Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Department of Pharmacology and Toxicology, The Brody School of Medicine, East Carolina University, Greenville, NC, USA.
Adv Exp Med Biol. 2019;1193:1-33. doi: 10.1007/978-981-13-6260-6_1.
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.
已有几篇综述文章分别论述了乙醛和其他乙醇代谢物的神经行为作用，以及癌症、肝脏和肺部疾病等主要与酒精相关的疾病。然而，很少有综述涉及酒精代谢在酒精对心脏和自主神经的不良作用及其潜在机制中的作用，特别是在脆弱人群中。在这一章中，简要概述了酒精剂量相关的心血管有利和不利影响后，我们讨论了乙醇代谢在其对脑干和心脏的不利影响中的作用。值得注意的是，由于乙醛在体内的组织水平较低，目前的知识排除了乙醛在酒精的不良自主神经和心脏作用中的主要作用。与男性和雄性啮齿动物的这些发现相反，女性和高血压个体对相似量的酒精的不良心脏作用更为敏感。为了理解这种差异，我们在高血压模型，自发性高血压大鼠（SHR）和雌性大鼠中讨论了酒精及其代谢物乙醛对自主神经和心脏的作用。我们提供的证据表明，增强的过氧化氢酶活性有助于高血压（代偿性）和雌激素存在下（固有）的心脏保护，但由于过氧化氢酶催化酒精代谢为乙醛，这种活性变得有害。值得注意的是，SHR 和去雌激素或补充正常血压大鼠的研究表明，乙醛通过（i） Akt/细胞外信号调节激酶（ERK）/一氧化氮合酶（NOS）级联和（ii）雌激素受体-α（ERα）介导的更高的过氧化氢酶活性，在自主神经核和心脏中引发氧化应激，从而触发氧化应激。后者得到了 ERα 阻断或过氧化氢酶抑制减弱酒精引起的心肌氧化应激和功能障碍的能力的支持。需要更多的机制研究来进一步了解这一公共卫生问题的机制。
