DIRECT AND REFLEX FUNCTIONS OF AFFERENT RENAL NERVES

传入肾神经的直接和反射功能

• 批准号: 3367376
• 负责人: NICHOLAS G MOSS
• 金额: $ 15.78万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3367376
• 关键词: afferent nerve; angiotensin II; baroreceptors; body fluids; calcitonin gene related peptide; electrophysiology; homeostasis; kidney circulation; kidney function; laboratory rat; neurotransmitters; norepinephrine; radioimmunoassay; saluresis; single cell analysis; substance P; sympathetic nervous system

The renal nerves play a central role in the neurogenic control of body fluid homeostasis. The overall objective of this study is to investigate the role of afferent renal nerves in this process. Subtypes of renal afferent nerves are responsible to vascular, tubular, and hormonal factors in the kidney, but it is not known if these diverse stimuli exert specific reflex responses in efferent renal sympathetic activity. In addition, the afferent renal nerves belong to a group of nerves that release neuropeptides from their sensory endings. The principal neuropeptides reported in afferent renal nerves are substance P (SP), a natriuretic agent, and calcitonin gene related peptide (CGRP), a vasodilator. These are important modulators of local vascular resistance in many tissues but the functional significance of neuropeptide release in the kidney is not known. Pilot studies have demonstrated significant spillover of neuropeptide into the renal pelvis during activation of renal chemoreceptors and an inhibitory activity on vasoconstriction. The specific aims of these studies are: 1) to investigate the specificity of renorenal and renovisceral reflexes at the single efferent unit level and 2) to investigate the role of neuropeptides released from renal afferent nerves on renal vascular and tubular function. Methods: Aim 1 will involve electrophysiological recordings of sympathetic efferent activity in renal and genitofemoral nerves of anesthetized rats. Activity in individual efferent fibers will be measured and analyzed during a series of interventions designed to stimulate specific groups of renal afferent nerves and systemic arterial baroreceptors. Comparison of the responses of individual fibers to several stimuli will show the specificity of reflexes with respect to the target organ and the initiating afferent fibers. In Aim 2, SP and CGRP will be infused into the renal artery at physiological rates to investigate their action on renal excretory function by clearance techniques and on the renal vasculature from their ability to counteract the renal vasoconstrictor effects of angiotensin II and norepinephrine. The same techniques will be used to study the effects of endogenous SP and CGRP release during stimulation of afferent renal nerves. Selective antagonists will identify the effects of each neuropeptide on hemodynamic and excretory function. Neuropeptide release will be measured by radioimmunoassay and correlated with the activation of selected subtypes of renal afferent nerves. Significance: 1) These studies will provide new data on the specificity of renorenal reflex control of renal function at the single fiber level. 2) The importance of neuropeptide release from renal afferent nerves in the control of renal vascular and excretory function will be investigated for the first time.

肾神经在身体的神经源控制中起着核心作用 液体稳态。 这项研究的总体目的是 研究传入肾神经在此过程中的作用。 亚型 肾脏的神经负责血管，管状和 肾脏中的激素因素，但尚不清楚这些多样 刺激在传出的肾同情中发挥特定的反射反应 活动。 此外，传入的肾神经属于一组 神经肽从其感觉末尾释放的神经。 这 在传入肾神经中报道的主要神经肽是物质 p（sp），亚位毒剂和降钙素基因相关肽（CGRP）， 血管扩张器。 这些是局部血管的重要调节剂 在许多组织中的抗性，但功能意义 肾脏中的神经肽释放尚不清楚。 试点研究 显示出明显的神经肽溢出到肾骨盆中 在激活肾化学感受器和对抑制活性的过程中 血管收缩。 这些研究的具体目的是：1） 调查在 单一发出的单位水平和2）调查 肾血管上肾脏神经释放的神经肽和 管状功能。 方法：AIM 1将涉及电生理学 肾脏和生殖股的交感性传出活性的记录 麻醉大鼠的神经。 单个传出纤维的活性 将在设计的一系列干预措施中测量和分析 刺激特定的肾脏传入神经和全身性的组 动脉压力感受器。 比较个人的反应 对几种刺激的纤维将显示反射的特异性 尊重目标器官和启动传入纤维。 目标 2，SP和CGRP将在生理时注入肾动脉 通过调查其对肾脏排泄功能的行动的比率 清除技术和肾脏脉管系统的能力 抵消血管紧张素II和 去甲肾上腺素。 相同的技术将用于研究效果 刺激传入肾脏期间内源性SP和CGRP释放的 神经。 选择性拮抗剂将识别每个的影响 血液动力学和排泄功能上的神经肽。 神经肽 释放将通过放射免疫测定法进行测量，并与 激活肾脏传入神经的选定亚型。 意义： 1）这些研究将提供有关培训特异性的新数据 在单光纤水平上对肾功能的反射控制。 2） 神经肽从肾脏传入神经释放的重要性 将研究肾血管和排泄功能的控制 首次。