MICROPUNCTURE STUDY OF KIDNEY FUNCTION

我们建议继续研究肾脏和肾单位的功能，并 调查导致或涉及以下异常的机制 青年自发肾血流动力学控制系统的观察 Okamoto-Aoki品系高血压大鼠(SHR)与 Wistar-京都血压正常对照：肾血管阻力升高； 高反应性肾小球对肾小球功能的反馈控制； 肾血管对血管紧张素和血栓素的高反应性； 肾小球血栓素受体密度增加。显微穿刺术和 微灌注技术将用于测量肾小球功能和 它受肾小管球反馈的控制。血液流动研究将 评价肾血管阻力的稳态和动态反应 身体和荷尔蒙的影响。放射性配基研究将量化 肾小球受体。三项协议将调查这一机制(S) 对过度的肾血管收缩负责；两个方案将 检查肾小管球反馈的夸大活动。研究将会 评估反馈活动已重置且更具反应性的建议 由于肾内血管收缩激素活性增加(S) 作为血管紧张素和血栓素和/或相对缺乏的 血管扩张激素(S)激动素等的作用。相对的 肌源性反应和管球反馈对血液的贡献 幼年自发性高血压患者的血流自动调节将被确定。假设 更有效的肾血流自动调节是由于夸大了 肾小管球反馈活动和/或更强的肌源性反应 将会被调查。血管活性激素/类耳石激素对血管紧张素转换酶活性的影响 血管舒张性张力的内源性控制器的相对强度 将会被检查。研究将检验夸大肾脏的假设 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，以及 血管扩张剂前列腺素E_2和前列腺素G_1_2与血管内皮生长因子的相互作用 血管收缩药血管紧张素II和血栓素II将在 血液流动研究。PGE2和PGl2的受体将在 从幼年自发性高血压大鼠分离的肾小球。肾小球血栓素A的调节 受体将被评估为肾内浓度的函数 血栓素。对年轻的遗传性高血压大鼠和 适当的正常血压控制应该提供新的、有用的和 对肾功能的作用及其调节的重要见解 发育中的内源性机制及激素和类金龟板系统 在人类原发性高血压的标准模型中研究高血压。

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.