Enhanced cardiac sympathetic afferent reflex in CHF

CHF 患者心脏交感神经传入反射增强

• 批准号: 6815913
• 负责人: WEI WANG
• 金额: $ 24.13万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2004-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6815913
• 关键词: afferent nerve; angiotensin II; baroreceptors; baroreflex; biological models; cardiovascular function; chemoreceptors; congestive heart failure; exercise; free radical oxygen; free radicals; heart pharmacology; hormone regulation /control mechanism; laboratory rat; lidocaine; myocardial ischemia /hypoxia; neuropathology; neuropharmacology; neuroregulation; neurotoxins; neurotransmitters; oxidative stress; oxidizing agents; reflex; sympathetic nervous system; afferent nerve; angiotensin II; baroreceptors; baroreflex; biological models; cardiovascular function; chemoreceptors; congestive heart failure; exercise; free radical oxygen; free radicals; heart pharmacology; hormone regulation /control mechanism; laboratory rat; lidocaine; myocardial ischemia /hypoxia; neuropathology; neuropharmacology; neuroregulation; neurotoxins; neurotransmitters; oxidative stress; oxidizing agents; reflex; sympathetic nervous system

DESCRIPTION (provided by applicant): Heart failure is characterized by an elevation in sympathetic tone. The mechanisms responsible for the sympatho-excitation in heart failure are not completely understood. Recent studies from this laboratory indicate that the cardiac "sympathetic afferent" reflex is enhanced and the baroreceptor reflex is blunted in heart failure. The augmented cardiac sympathetic afferent reflex and the blunted baroreceptor reflex are mediated by increases in central angiotensin II in heart failure. So far the mechanism(s) responsible for these reflex interactions in the heart failure state are not completely clear. Based on preliminary data we hypothesize that the augmentation of the cardiac sympathetic afferent reflex is mediated by central angiotensin II and reactive oxidant stress in the heart failure state. To better understand the mechanisms responsible for augmentation of the cardiac sympathetic afferent reflex we propose the following specific aims: 1) To determine if reactive oxygen species mediates the augmented cardiac sympathetic afferent reflex by elevated central angiotensin II in heart failure; 2) To determine if the cardiac sympathetic afferent reflex blunts the baroreceptor reflex and if the blunted baroreflex in animals with heart failure is restored by removal of cardiac sympathetic afferent input with epicardial application of lidocaine or depletion of cardiac sympathetic afferent neurotransmitters by the epicardial application of the ultrapotent neurotoxin resiniferatoxin, and to determine if central angiotensin II and free radicals play an important role in the blunted baroreceptor reflex by activation of the cardiac sympathetic afferent pathway in rats with heart failure; 3) To determine if the cardiac sympathetic afferent reflex augments the chemoreceptor reflex and if the enhanced chemoreceptor reflex in animals with heart failure is restored by removal of cardiac sympathetic afferent input with epicardial application of lidocaine or resiniferatoxin and to determine if central angiotensin II and free radicals play an important role in the chemoreceptor reflex by activation of cardiac sympathetic afferents in rats with heart failure; and finally 4) To determine if exercise training normalizes the enhanced cardiac sympathetic afferent reflex, the augmented chemoreceptor reflex, and the blunted baroreceptor reflex in rats with heart failure by decreasing angiotensin II and free radicals. These reflex interactions regulate sympathetic outflow in heart failure. The abnormal sympatho-excitation in the heart failure state is likely to be mediated by a variety of peripheral inputs with important modulation by central substances. If the cardiac sympathetic afferent reflex and baroreceptor reflex are two of the reflexes which contribute to sympathetic activation in heart failure, a comprehensive understanding of neuro-humoral regulation of this reflex may result in more definitive and rational therapy targeted to the sympathetic nervous system in this disease state.

描述（由申请人提供）：心力衰竭的特征是同情语调的高程。尚未完全理解导致心力衰竭交感神经的机制。该实验室的最新研究表明，心脏“心力衰竭”的心力衰竭会增强心脏“交感神经”反射。增强的心脏交感传入反射和钝化的压力感受器反射是通过心力衰竭中央血管紧张素II的增加来介导的。到目前为止，在心力衰竭状态下负责这些反射相互作用的机制尚不完全清楚。基于初步数据，我们假设心脏衰竭状态下的中央血管紧张素II和反应性氧化剂应激介导心脏交感传入反射的增强。为了更好地理解负责增强心脏交感传入反射的机制，我们提出了以下特定目的：1）确定活性氧是否通过心力衰竭中升高的中央血管紧张素II介导增强的心脏交感神经传入反射； 2）确定心脏交感神经反射是否会钝化压力感受器反射，以及是否通过去除心脏症的心脏交感神经输入来恢复心力衰竭的动物中的压力反射，并在心外膜上施用lidocaine或通过心脏deption剂量施加心脏症或通过心脏交感神经交感神经交感神经促进剂的extifters neurotanters sneurotinters sneurotinters sneurotinters sepatife neurotenters seminent s risterters a并确定中央血管紧张素II和自由基是否通过激活心力衰竭的大鼠心脏交感神经传入途径在钝化的压力感受器反射中起重要作用； 3）确定心脏交感神经的反射是否会增强化学感受器反射，以及是否通过去除心外膜的心外膜输入的心脏交感神经输入来恢复具有心力衰竭的动物的化学感受器反射，并通过lidocaine或radicection扮演中心蛋白II扮演的角色，并确定Chargiotect emector ii the Chargiotect a Chentice in II nectie in II nectie symection incemptrial ii soctorec wemection in II nytical symection在心力衰竭的老鼠传入；最后4）为了确定运动训练是否使增强的心脏交感神经传入反射，增强的化学感受器反射以及通过减少血管紧张素II和自由基的心力衰竭的大鼠中钝化的压力感受器反射。这些反射相互作用调节心力衰竭的交感神经流出。心力衰竭状态下的异常交感神经激发可能是由各种中央物质调节的多种外围输入介导的。如果心脏交感神经反射和压力感受器反射是有助于心力衰竭交感神经激活的两种反射，那么对这种反射的神经幽默调节的全面理解可能会导致对这种疾病状态的交感神经系统的更确定和合理的治疗。