权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

CHOLINERGIC ACTIVATION: AUTOMATICITY AND CONDUCTION

胆碱能激活：自动性和传导

基本信息

批准号：
3340183
负责人：
JEROD M LOEB
金额：
$ 8.82万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1982
资助国家：
美国
起止时间：
1982-07-01 至 1987-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3340183
关键词：
acetylcholine arrhythmia atrioventricular node cholinergic agents heart circulation heart contraction heart pharmacology

项目摘要

The cardiovascular effects of acetylcholine include alterations in automaticity, conduction, coronary blood flow and contractility. Although marked differences are apparent with respect to these actions, little consensus regarding mechanism has been reached. The present investigation is directed toward an analysis of differences between muscarinic effects on cardiac automaticity and conduction. Recent evidence suggests that potential inhomogeneities in muscarinic receptor behavior might underlie some of these differences. Moreover, we have found that cholinergic efficacy at the sinus node is profoundly modulated by the perfusion characteristics of acetylcholine delivered through the sinus node artery. Whether this factor contributes to differences in cholinergic responsiveness is, however, unknown. Thus, experiments are planned which will analyze potential interrelationships between pharmacological and mechanical effects of acetylcholine on the sinus and AV nodes. Agonist and/or antagonist drugs will be administered via the sinus and AV node arteries under rigidly controlled perfusion conditions. The differences between muscarinic responses to vagal stimulation and exogenous agonist administration will be explored. Additional experiments will ascertain whether differences in complex autonomic interactions (ie: accentuated antagonism) are responsible for differences in cholinergic efficacy at the sinus and AV nodes. The information derived from these studies will be of importance in delineating more clearly the complex effects of parasympathetic activation on the heart. Further understanding of parasympathetic mechanisms involved in normal cardiac function (automaticity and conduction) is essential for a complete understanding of the alterations in neural control evident in pathophysiological states. The possibility for the existence of inhomogeneities in muscarinic receptor subtypes within the heart may provide the impetus for the development of new pharmacologic agents which could selectively influence cholinergic function in the heart.

乙酰胆碱对心血管的影响包括：自律性、传导、冠状动脉血流量和收缩性。虽然这些行动之间存在明显差异，但差异不大就机制问题达成了共识。本研究是针对毒蕈碱作用之间的差异进行分析，心脏自律性和传导。最近的证据表明毒蕈碱受体行为的潜在不均匀性可能是其中的一些差异。此外，我们还发现，窦房结处的功效受到灌注的深刻调节通过窦房结动脉输送的乙酰胆碱的特征。这个因素是否会导致胆碱能神经元然而，反应是未知的。因此，计划进行的实验将分析药理学和乙酰胆碱对窦和房室结的机械作用。激动剂和/或拮抗剂药物将通过窦和AV给药在严格控制的灌注条件下的结动脉。的迷走神经刺激和外源性刺激的毒蕈碱反应之间的差异将探索激动剂施用。其他实验将确定复杂自主交互的差异（即：增强的拮抗作用）是导致胆碱能神经递质的差异的原因。窦和房室结的疗效。从这些研究中获得的信息将对更清楚地描绘了副交感神经激活的复杂效应在心脏上进一步了解副交感神经机制在正常心脏功能（自律性和传导）中，完全理解神经控制的变化，病理生理状态。存在的可能性心脏内毒蕈碱受体亚型的不均一性可能为开发新的药物制剂提供动力，可以选择性地影响心脏的胆碱能功能。