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Cardiac afferents and renal function in heart failure

心力衰竭中的心脏传入和肾功能

基本信息

批准号：
10558561
负责人：
Hanjun Wang
金额：
$ 57.17万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-18 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10558561
关键词：
Ablation Acute myocardial infarction Affect Afferent Neurons American Capsaicin Cardiac Cardiac Output Cardiorenal syndrome Cardiovascular Diseases Cardiovascular system Cells Central venous pressure Chest Chronic Clinical Complication Congestive Heart Failure Conscious Coupled Data Denervation Development Diastolic blood pressure Epidemic Exhibits Fiber Functional disorder Genetic Grant Heart Heart Injuries Heart failure Hypothalamic structure Injury to Kidney Ischemia Kidney Kidney Failure Laboratories Left Low Cardiac Output Measures Mediating Medical Metabolic Modeling Morbidity - disease rate Myocardial Infarction Nerve Neural Pathways Neurons Neurotoxins Newly Diagnosed Pathogenesis Pathway interactions Patients Persons Plasma Play Prognosis Progressive Disease Rat Transgene Rattus Reflex action Reflex control Renal Blood Flow Renal function Renin-Angiotensin-Aldosterone System Resiniferatoxin Rodent Model Role Sensory Societies Spinal Spinal Ganglia Syndrome TRPV1 gene Techniques Testing Therapeutic Thinking United States Vascular resistance Vasoconstrictor Agents Vasopressins Venous Ventricular Vertebral column Work analog conventional therapy cytokine designer receptors exclusively activated by designer drugs genetic approach hemodynamics hypoperfusion improved innovation kidney dysfunction kidney vascular structure magnocellular mortality neural novel novel therapeutics paraventricular nucleus prevent receptor renal ischemia systemic inflammatory response therapy development vasoconstriction

项目摘要

Project Summary Chronic heart failure (CHF) is a growing epidemic in western societies. In the United States alone, approximately 6 million people live with CHF. In late stage CHF, renal failure is a complication that results in worsening heart failure. Patients exhibiting the cardio-renal syndrome have an extremely poor prognosis. Medical therapy for this syndrome has been ineffective. A new way of thinking about the mechanisms responsible for worsening renal function in CHF is necessary. During the previous cycle of this grant we elucidated an important neural pathway that not only mediates cardiac remodeling but also drives a massive increase in cardiac, renal and global sympathetic nerve activity in CHF. Ablation of this pathway markedly improves survival in the post MI-CHF rodent model. The Cardiac Sympathetic Afferent Reflex (CSAR) is mediated, in large part, by epicardial, TRPV1 receptor-expressing sensory endings whose cell bodies reside in the thoracic dorsal root ganglia. Here, we propose to build on our previous work by demonstrating an important role for cardiac spinal afferents in mediating renal dysfunction in severe CHF. Based on our preliminary data and using a novel TRPV1 Cre rat coupled with chemogenetic excitation and inhibition we will demonstrate the important role that these afferents play in the pathogenesis of the cardio-renal syndrome. We will furthermore utilize the ultrapotent neurotoxin resiniferatoxin (RTX; TRPV1 specific) to therapeutically salvage renal function in CHF. These studies are highly relevant to the clinical situation and will pave the way for a novel and innovative alternative to conventional therapy.

项目摘要慢性心力衰竭(CHF)在西方社会是一种日益流行的疾病。仅在美国，大约有600万人患有CHF。在慢性心力衰竭晚期，肾功能衰竭是一种并发症，可导致心力衰竭恶化。表现为心肾综合征的患者预后极差。对这种综合症的药物治疗一直无效。关于机构学的一种新思路对CHF患者肾功能恶化负责是必要的。在这笔赠款的上一个周期中，我们阐明了一条重要的神经通路，它不仅介导心脏重构，而且还驱动大量的 CHF患者的心、肾和全心交感神经活动增加。显著消融这条通路改善MI-CHF后啮齿动物模型的存活率。心脏交感传入反射(CSAR)是在很大程度上，由心外膜介导的TRPV1受体表达的感觉终末，其细胞体驻留在胸背根神经节。在这里，我们建议在以前工作的基础上，演示一个重要的心脏脊髓传入神经在严重充血性心力衰竭肾功能障碍中的作用。根据我们的初步数据并使用一种新型的TRPV1 Cre大鼠，结合化学发生的兴奋和抑制，我们将展示这些传入物质在心肾综合征的发病机制中起着重要作用。我们将进一步利用超强神经毒素树脂毒素(RTX；TRPV1特异性)治疗挽救肾功能以瑞士法郎计算。这些研究与临床情况高度相关，并将为新的和传统疗法的创新替代方案。

项目成果

期刊论文数量（20）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mineralocorticoids: the secret of muscle reflex dysfunction in hypertension?

盐皮质激素：高血压肌反射功能障碍的秘密？

DOI：
10.1152/ajpheart.00501.2017
发表时间：
2017
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
0
作者：
Wang,Han-Jun
通讯作者：
Wang,Han-Jun

Time-dependent alteration in the chemoreflex post-acute lung injury.

DOI：
10.3389/fphys.2022.1009607
发表时间：
2022
期刊：
FRONTIERS IN PHYSIOLOGY
影响因子：
4
作者：
Kamra, Kajal;Karpuk, Nikolay;Adam, Ryan;Zucker, Irving H.;Schultz, Harold D.;Wang, Han-Jun
通讯作者：
Wang, Han-Jun

Integrative Physiological Aspects of Brain RAS in Hypertension.