AUTONOMIC RECEPTOR FUNCTION IN LV HYPERTROPHY & FAILURE

首席调查员和她的同事们已经确定 β-肾上腺素能和M受体的几个变化 左心室功能与腺苷环化酶活性 肥大和失败。这些包括：1)测试版的减少- 左侧肾上腺素能受体高亲和力激动剂结合部位 心力衰竭，2)M受体密度降低 左心衰，3)腺苷环化酶活性降低。 左心衰，以及4)减少毒碱抑制。 左心衰患者的腺苷环化酶活性。第一 这个应用程序的目标是描绘生物化学 这些变化背后的机制。这将是 通过1)识别可能改变的受体来完成- β-肾上腺素能受体的光亲和标记蛋白质 双向电泳法鉴定分子 人β-肾上腺素能受体的重量和等电点 左心室肥厚动物的左心室 2)鸟嘌呤核苷酸调节蛋白检测失败 左心室肥厚和衰竭的功能。第二 本应用程序的目标是定义时间进程和概括性 有缺陷的人。这将通过检查1)另一个 左心室肥厚模型，即肾性高血压，2) 高亲和力β-肾上腺素能受体变化的研究进展 M受体激动剂结合、M受体密度和调节 腺苷环化酶活性与左心室功能 左心室肥厚从轻度发展到重度 肥大，3)正常左、右肾上腺素能受体的变化 心室肥厚和衰竭，4)α-受体的变化 肾上腺素能受体。本申请的第三个目标是 测定心肌缺陷的选择性 使用纯化的肌膜制剂，最后进行了研究。 分离心肌细胞以去除大部分非心肌细胞组织 在制备膜之前。有人建议，这些研究 将增强我们在细胞水平上对其中一种 临床心脏病学中最重要的问题，即左 心脏肥厚和心力衰竭。

The principal investigator and her colleagues have identified several alterations in beta-adrenergic and muscarinic receptor function and adenylate cyclase activity in left ventricular hypertrophy and failure. These include: 1) decreases in the beta- adrenergic receptor high affinity agonist binding sites in left ventricular failure, 2) decreases in muscarinic receptor density in left ventricular failure, 3) decreased adenylate cyclase activity in left ventricular failure, and 4) decreased muscarinic inhibition of adenylate cyclase activity in left ventricular failure. The first goal of this application is to delineate the biochemical mechanisms underlying these alterations. This will be accomplished by 1) identifying a potentially altered receptor- protein by photoaffinity labelling of the beta-adrenergic receptor and two dimensional electrophoresis to identify the molecular weight and isoelectric point of the beta-adrenergic receptor in the left ventricular of animals with left ventricular hypertrophy and failure, 2) to examine guanine nucleotide regulatory protein function in left ventricular hypertrophy and failure. The second goal of this application is to define the time course and generality of the defects. This will be accomplished by examining 1) another model of left ventricular hypertrophy, i.e. renal hypertension, 2) the progression of changes in high affinity beta-adrenergic and muscarinic agonist binding, muscarinic density and modulation of adenylate cyclase activity and function as left ventricular hypertrophy progresses from mild to severe left ventricular hypertrophy, 3) changes in adrenergic receptors in normal, left ventricular hypertrophy, and failure, 4) changes in alpha- adrenergic receptors. The third goal of the present application is to determine the selectivity of defects for cardiac muscle by using a purified sarcolemma preparation and finally the study of isolated myocytes to remove most of the non-myocyte tissue before preparing membranes. It is proposed that these studies will enhance our understanding at the cellular level, of one of the most important problems in clinical cardiology, i.e., left ventricular hypertrophy and heart failure.