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在酒精性心肌病发生之前,慢性乙醇处理过程中心脏信号转导系统的变化。

Changes in cardiac signal transduction systems in chronic ethanol treatment preceding the development of alcoholic cardiomyopathy.

作者信息

Strasser R H, Nüchter I, Rauch B, Marquetant R, Seitz H

机构信息

University of Heidelberg, Department of Cardiology, Pulmology and Angiology.

出版信息

Herz. 1996 Aug;21(4):232-40.

PMID:8805003
Abstract

Chronic alcohol consumption has been postulated as an important pathogenetic mechanism for the development of alcoholic cardiomyopathy. This form of chronic heart failure shares with other forms of cardiomyopathy the pronounced alterations of the adrenergic signal transduction systems. These alterations include a significant reduction of beta-adrenergic receptors and a reduced responsiveness of the adenylyl cyclase. Changes of other receptor systems such as alpha-adrenergic and muscarinic receptors have not been studied extensively so far. To address the question if changes of the adrenergic signal transduction systems may occur early in the development of alcoholic cardiomyopathy and if alpha 1-adrenergic receptors and muscarinic receptors may be subjected to an altered expression even before severe impairment of the left ventricular function becomes obvious, rats were chronically fed with an alcohol diet containing 35% of total calorie intake as ethanol. In cardiac plasma membranes beta-adrenergic receptors, alpha 1-adrenergic receptors, muscarinic receptors and adenylyl cyclase activities were determined after 4 and 8 weeks of chronic alcohol treatment. After these periods of chronic alcohol diet no signs of overt heart failure such as pleural effusion or increased lung wet weight as parameters for congestion were present. Body weight gain was comparable in the controls and under chronic alcohol treatment in these adolescent rats. Both after 4 and 8 weeks of chronic alcohol treatment the density of cardiac beta-adrenergic receptors remained unchanged and all adenylyl cyclase activities remained fully responsive. In contrast, after 8 weeks of alcohol treatment the developmental increase of cardiac muscarinic receptors in the adolescent rats was greatly impaired resulting in a significantly reduced expression of these receptors even before clinical signs of heart failure. In contrast the density of cardiac alpha 1-adrenergic receptors were significantly reduced already after 4 weeks of chronic alcohol treatment with an additional impairment of the developmental increase after 8 weeks of alcohol treatment. These data characterize for the first time early changes of cardiac receptor system in chronic alcohol treatment which precede the development of overt heart failure. These changes include alpha 1-adrenergic and muscarinic receptors, but in contrast to severe heart failure, leave the beta 1-adrenergic system and the responsiveness of the adenylyl cyclase intact. Additionally these data show the developmentally increased expression of cardiac alpha 1-adrenergic and muscarinic receptors in rat heart.

摘要

长期饮酒被认为是酒精性心肌病发生发展的一种重要发病机制。这种慢性心力衰竭形式与其他类型的心肌病一样,肾上腺素能信号转导系统存在明显改变。这些改变包括β - 肾上腺素能受体显著减少以及腺苷酸环化酶反应性降低。迄今为止,其他受体系统如α - 肾上腺素能受体和毒蕈碱受体的变化尚未得到广泛研究。为了探讨在酒精性心肌病发展早期肾上腺素能信号转导系统是否会发生变化,以及在左心室功能严重受损明显之前,α1 - 肾上腺素能受体和毒蕈碱受体的表达是否会发生改变,将大鼠长期喂食含35%总热量乙醇的酒精饮食。在慢性酒精处理4周和8周后,测定心脏质膜中的β - 肾上腺素能受体、α1 - 肾上腺素能受体、毒蕈碱受体和腺苷酸环化酶活性。在这些慢性酒精饮食期后,没有出现明显心力衰竭的迹象,如胸腔积液或肺湿重增加等充血参数。在这些青春期大鼠中,对照组和慢性酒精处理组的体重增加相当。慢性酒精处理4周和8周后,心脏β - 肾上腺素能受体密度均保持不变,所有腺苷酸环化酶活性均保持充分反应性。相反,酒精处理8周后,青春期大鼠心脏毒蕈碱受体的发育性增加受到极大损害,甚至在心力衰竭临床症状出现之前,这些受体的表达就显著降低。相比之下,慢性酒精处理4周后,心脏α1 - 肾上腺素能受体密度就显著降低,酒精处理8周后其发育性增加进一步受损。这些数据首次描述了慢性酒精处理中心脏受体系统在明显心力衰竭发生之前出现的早期变化。这些变化包括α1 - 肾上腺素能受体和毒蕈碱受体,但与严重心力衰竭不同的是,β1 - 肾上腺素能系统和腺苷酸环化酶的反应性保持完整。此外,这些数据显示了大鼠心脏中α1 - 肾上腺素能受体和毒蕈碱受体在发育过程中的表达增加。

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