ETHANOL AND ADENOSINERGIC ACTIONS IN THE HEART

乙醇和腺苷在心脏中的作用

基本信息

批准号：
2457495
负责人：
RICHARD ALLAN FENTON
金额：
$ 7.66万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-08-01 至 1999-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2457495
关键词：
G protein adenosine alcoholism /alcohol abuse beta antiadrenergic agent cardiotonic agents drug interactions ethanol heart contraction high performance liquid chromatography laboratory rat neurotransmitter receptor receptor coupling statistics /biometry toxicant interaction western blottings

项目摘要

APPLICANT'S ABSTRACT: Alcohol abuse is a societal problem which exists with citizens from adolescence to the elderly. Chronic alcohol consumption has significant detrimental impact on the cardiovascular system, including the development of alcoholic heart muscle disease (AHMD). Subclinical depression of heart function observed with alcohol use is also associated with arrhythmogenesis, including ventricular tachycardia which may degenerate to fibrillation and sudden death. Circulating levels of the beta-adrenergic neurotransmitter, norepinephrine, are elevated with acute and chronic alcoholism. Beta- adrenergic overdrive is cardiotoxic, by inducing Ca2+ overload, and arrhythmogenic, by eliciting triggered automaticity. Adenosine normally released from the heart is an agent which attenuates the functional expression of beta-adrenoceptor activation (antiadrenergic action). Preliminary evidence presented herein indicates that the antiadrenergic action of adenosine is enhanced in the alcohol-treated heart. It is HYPOTHESIZED that the enhanced antiadrenergic action of adenosine provides protection for the heart against the action of high levels of norepinephrine observed in chronic alcoholism, thereby attenuating Ca2+ overload and arrhythmogenesis. The GOAL of this project is to study the mechanism(s) by which ethanol enhances the antiadrenergic action of adenosine. The experiments utilize techniques for assessing contractile function and receptor transduction at the organ and membrane levels. The Specific Aims are to determine, with the isolated perfused heart and cardiomyocyte preparations, the effects of chronic ethanol treatment on the antiadrenergic action of adenosine with respect to contractile function (LVP, left ventricular pressure; +dPt max, the rate of pressure development; -dP/dT max, the rate of relaxation) and G protein expression. Results obtained from the proposed experiments will enhance our understanding of processes which, in the future, may be utilized to reduce injury in the alcoholic myocardium.

申请人的摘要：酗酒是一个存在的社会问题从青春期到老年人的公民。慢性酒精消费对心血管产生重大不利影响系统，包括酗酒心肌疾病的发展（ahmd）。酒精观察到心脏功能的亚临床抑郁症使用也与心律失常有关，包括心室心动过速可能会退化为原纤维和猝死。 β-肾上腺素能神经递质的循环水平，去甲肾上腺素，急性和慢性酒精中毒升高。 β- 肾上腺素过度驱动是心脏毒性的，通过诱导Ca2+过载和心律失常，通过引发触发自动化。腺苷通常发自内心释放的是衰减功能的代理 β-肾上腺素受体激活的表达（抗氧化作用）。本文提供的初步证据表明抗氧化能力在酒精处理的心脏中，腺苷的作用增强了。这是假设腺苷增强的抗氧化能力作用为心脏提供保护，以防止高水平的作用在慢性酒精中毒中观察到的去甲肾上腺素，从而衰减Ca2+ 过载和心律失常。该项目的目的是研究乙醇增强抗氧化作用的机制腺苷。实验利用技术评估收缩器官和膜水平的功能和受体转导。具体目的是用孤立的灌注心脏确定心肌细胞制剂，慢性乙醇治疗对腺苷关于收缩的抗氧化能力作用功能（LVP，左心压； +DPT最大，压力速率发展; -dp/dt max，放松速率）和G蛋白表达。从提出的实验中获得的结果将增强我们对将来可能会利用的过程的理解减少酒精心肌的受伤。