RENAL NERVES AND CENTRAL MONOAMINES IN HYPERTENSION

高血压中的肾神经和中枢单胺

• 批准号: 3449463
• 负责人: RICHARD H ALPER
• 金额: $ 5.08万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 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/3449463
• 关键词: afferent nerve; brain stem; denervation; dopamine; hypothalamus; kidney circulation; nerve; neurochemistry; neurotransmitters; norepinephrine; renal artery obstruction; serotonin; vascular resistance

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

传入肾神经在心血管调节中的作用是 有争议的。 尽管有大量数据，但几乎没有达成共识 传入肾神经刺激的心血管后果。 研究 但是，确实建议肾血管高血压被肾脏逆转 去神经，因为反射降低了传出性交感神经和动脉 压力。 这可能是由下丘脑去甲肾上腺素介导的。 迄今为止 与传入肾神经有关的实验证据很少 中央单胺代谢的活性，尽管间接证据 确实存在。 在有意识的大鼠中，肾狭窄（RST）之后 脱落和卡托普利，以及心动激肽的肾内输注 增加动脉压和交感神经活动。 这些影响 事先对肾脏的脱落来废除。 这两个型号将 允许研究中央单胺在传入肾脏中的功能作用 有意识大鼠的神经依赖性心血管反应。 该项目将尝试提供有关该项目的重要新信息 单胺在特定大脑区域的能力改变了各种 心血管参数。 第一批研究将描述 肾脏的神经保护和剥夺的综合和代谢 下丘脑和脑干单胺。 第二个研究将 描述RST和肾内心动激素对中央生物源的影响 胺动力学。 这些实验旨在提供有关 特定的中央部位和神经递质介导心血管 对传入肾神经依赖性刺激的反应。 最终研究 将使用初始实验中的数据并探索其功能 重要性。 这是通过进行特定的本地中断来完成的 在神经化学研究中涉及的神经递质途径中。 在局部中央注射利多卡因，特定受体 激动剂，拮抗剂和神经毒素或离散的电解病变， 心血管对RST和/或肾内心动激素的反应将是 观察到。 通过这种方式，对网站和网站的系统描述 与中心介导的传入肾神经有关的神经递质 反射和心血管生理学将发展。 这将提供 深入了解中心，心血管和神经机制 高血压的发病机理