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

RENAL NERVES AND CENTRAL MONOAMINES IN HYPERTENSION

高血压中的肾神经和中枢单胺

基本信息

批准号：
3449464
负责人：
RICHARD H ALPER
金额：
$ 4.06万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-07-01 至 1989-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3449464
关键词：
afferent nerve brain stem denervation dopamine hypothalamus kidney circulation laboratory rat nerve neurochemistry neurotransmitters norepinephrine renal artery obstruction serotonin vascular resistance

项目摘要

The role of afferent renal nerves in cardiovascular regulation is controversial. Despite a large body of data, there is little agreement on cardiovascular consequences of afferent renal nerve stimulation. Studies do suggest, however, that renovascular hypertension is reversed by renal denervation, as a reflex decrease in efferent sympathetic tone and arterial pressure. This may be mediated by hypothalamic norepinephrine. To date there is little experimental evidence relating afferent renal nerve activity to central monoamine metabolism, although circumstantial evidence does exist. In conscious rats, renal stenosis (RSt) following sino-aortic deafferentation and captopril, and the intrarenal infusion of bradykinin increase arterial pressure and sympathetic nerve activity. These effects are abolished by prior denervation of the kidney. The two models will permit studies on functional roles of central monoamines in afferent renal nerve-dependent cardiovascular responses in conscious rats. This project will attempt to provide significant new information on the ability of monoamines in specific brain regions to alter various cardiovascular parameters. The first studies will describe effects of renal denervation and deafferentation on the synthesis and metabolism of hypothalamic and brainstem monoamines. A second series of studies will describe the effects of RSt and intrarenal bradykinin on central biogenic amine dynamics. These experiments are intended to provide information on specific central sites and neurotransmitters that mediate cardiovascular responses to afferent renal nerve-dependent stimuli. The final studies will use data from the initial experiments and explore their functional importance. This is accomplished by making specific, local interruptions in neurotransmitter pathways implicated by the neurochemical studies. Following local central injections of lidocaine, specific receptor agonists, antagonists, and neurotoxins, or discrete electrolytic lesions, cardiovascular responses to RSt and/or intrarenal bradykinin will be observed. In this manner a systematic description of sites and neurotransmitters involved in centrally-mediated afferent renal nerve reflexes and cardiovascular physiology will evolve. This will provide insight into central, cardiovascular and neural mechanisms in the pathogenesis of hypertension

肾传入神经在心血管调节中的作用是有争议的。尽管有大量的数据，但几乎没有达成一致的意见肾传入神经刺激的心血管后果。研究然而，确实表明肾血管性高血压可以被肾脏逆转。失神经，作为传出交感神经张力和动脉的反射性减少压力。这可能是由下丘脑去甲肾上腺素调节的。到目前为止很少有实验证据表明与肾传入神经有关。中枢单胺代谢活性，尽管有间接证据确实存在。清醒大鼠窦主动脉后肾狭窄(RST) 去传入、卡托普利和肾内注射缓激肽增加动脉压和交感神经活性。这些影响通过预先失去肾脏的神经而被消灭。这两款车型将中枢单胺类神经递质在传入肾功能作用的研究进展清醒大鼠的神经依赖性心血管反应。这个项目将试图提供关于大脑特定区域中的单胺类物质改变各种心血管参数。第一项研究将描述肾去神经和去传入对肾上腺皮质激素合成和代谢的影响下丘脑和脑干单胺。第二系列研究将描述RST和肾内缓激肽在中枢生物发生中的作用胺类动力学。这些实验旨在提供以下方面的信息调节心血管的特定中枢部位和神经递质对肾神经传入依赖刺激的反应。期末研究将使用来自初始实验的数据并探索它们的功能重要性。这是通过进行特定的本地中断来实现的在神经化学研究所涉及的神经递质通路中。在局部中心注射利多卡因后，特异性受体激动剂、拮抗剂和神经毒素，或离散的电解性损伤， RST和/或肾内缓激肽的心血管反应将是观察到的。以这种方式系统地描述遗址和中枢性肾传入神经所涉及的神经递质反射和心血管生理学将会进化。这将提供对中枢、心血管和神经机制的洞察高血压的发病机制