MICROPUNCTURE STUDY OF KIDNEY FUNCTION

肾功能的微穿刺研究

• 批准号: 2209960
• 负责人: WILLIAM J ARENDSHORST
• 金额: $ 31.39万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2209960
• 关键词: angiotensins; atrial natriuretic peptide; chemoreceptors; familial hypertension; genetic strain; glomerular filtration; kidney circulation; mechanoreceptors; micropuncture; neurohormones; prostaglandins; renal tubular transport; saluresis; spontaneous hypertensive rat; thromboxanes; vasomotion

We propose to continue studies of kidney and nephron function and investigate mechanisms responsible for, or involved in, abnormalities in renal hemodynamic control systems we observe in young spontaneously hypertensive rats of the Okamoto-Aoki strain (SHR) as compared to Wistar-Kyoto normotensive controls: elevated renal vascular resistance; hyperreactive tubuloglomerular feedback control of glomerular function; hyper-reactive renal vasculature to angiotensin and thromboxane; and increased density of glomerular thromboxane receptors. Micropuncture and microperfusion techniques will be used to measure glomerular function and its control by tubuloglomerular feedback. Blood flow studies will evaluate steady-state and dynamic responses of renal vascular resistance to physical and hormonal influences. Radio-ligand studies will quantify glomerular receptors. Three protocols will investigate the mechanism(s) responsible for the excessive renal vasoconstriction; two protocols will examine exaggerated activity of tubuloglomerular feedback. Studies will evaluate the proposal that feedback activity is reset and more reactive due increased intrarenal activity of the vasoconstrictors hormone(s) such as angiotensin and thromboxane and/or a relative deficiency in the effects of vasodilator hormone(s) such as kinins. The relative contribution of myogenic responses and tubuloglomerular feedback to blood flow autoregulation in young SHR will be determined. The hypothesis that more efficient autoregulation of renal blood flow is due to exaggerated tubuloglomerular feedback activity and/or a stronger myogenic response will be investigated. The influence of vasoactive hormones/autacoids on the relative strengths of the intrinsic controllers of vasomotor tone will be examined. Studies will test the postulate that exaggerated renal vascular reactivity is due to greater responses to constrictor systems or weaker responses to dilator systems. Vascular reactivity to, and interactions among, the vasodilator prostanoids PGE2 and PGl2 and the vasoconstrictors angiotensin II and thromboxane will be determined in blood flow studies. Receptors for PGE2 and PGl2 will be characterized in glomeruli isolated from young SHR . Regulation of glomerular thromboxane receptors will be assessed as a function of intrarenal concentrations of thromboxane. Parallel studies in young genetically hypertensive rats and appropriate normotensive controls should provide new, useful and important insights into the role of renal function, and its regulation by intrinsic mechanisms and hormonal and autacoid systems in the development of hypertension in a standard model of human essential hypertension.

我们建议继续研究肾脏和肾单位功能 研究导致或参与异常的机制 我们在年轻人中自发观察到的肾脏血流动力学控制系统 冈本青木品系（SHR）高血压大鼠与 Wistar-Kyoto 正常血压对照：肾血管阻力升高； 肾小球功能的高反应性肾小管肾小球反馈控制； 肾血管系统对血管紧张素和血栓素反应过度；和 肾小球血栓素受体密度增加。 微穿刺和 微灌注技术将用于测量肾小球功能和 它通过肾小管反馈进行控制。 血流研究将 评估肾血管阻力的稳态和动态反应 身体和荷尔蒙的影响。 放射性配体研究将量化 肾小球受体。三个协议将研究其机制 造成肾血管过度收缩；两个协议将 检查肾小球反馈的夸大活动。 研究将 评估反馈活动已重置且更具反应性的提案 由于血管收缩激素的肾内活性增加，例如 如血管紧张素和血栓素和/或相对缺乏 血管舒张激素（如激肽）的作用。 亲戚 生肌反应和肾小球反馈对血液的贡献 年轻 SHR 中的流量自动调节将被确定。 假设 肾血流量更有效的自动调节是由于夸大 小管肾小球反馈活动和/或更强的肌源性反应 将被调查。 血管活性激素/自体激素对血管活性的影响 血管舒缩张力内在控制器的相对强度 将接受检查。 研究将检验夸大肾脏功能的假设 血管反应性是由于对收缩系统或 对扩张器系统的反应较弱。 血管反应性，和 血管扩张剂前列腺素 PGE2 和 PGl2 之间的相互作用 血管收缩剂血管紧张素 II 和血栓素将在 血流研究。 PGE2 和 PGl2 的受体将被表征为 从年轻的 SHR 中分离出肾小球。肾小球血栓素的调节 受体将根据肾内浓度的函数进行评估 血栓素。 对年轻遗传性高血压大鼠和 适当的正常血压控制应提供新的、有用的和 关于肾功能的作用及其调节的重要见解 发育中的内在机制以及激素和自体系统 人类原发性高血压标准模型中的高血压。