MICROPUNCTURE STUDY OF KIDNEY FUNCTION

我们建议继续研究肾脏和肾单位的功能， 调查负责或参与异常的机制， 我们在年轻人中观察到自发性肾血流动力学控制系统 Okamoto-Aoki品系高血压大鼠（SHR）与 血压正常对照组：肾血管阻力升高; 高反应性肾小管-肾小球反馈控制肾小球功能; 肾血管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。 显微穿刺和 微灌注技术将用于测量肾小球功能， 其控制由管球反馈。 血流研究将 评价肾血管阻力的稳态和动态反应 身体和荷尔蒙的影响。 放射性配体研究将量化 肾小球受体三个方案将研究机制 负责过度肾血管收缩;两个协议将 检查肾小管肾小球反馈的过度活动。 研究将 评估反馈活动重置和更具反应性的建议 由于血管收缩激素的肾内活性增加， 如血管紧张素和血栓素和/或血管紧张素和血栓素的相对缺乏， 血管扩张激素如激肽的作用。 的相对 肌源性反应和管球反馈对血液的贡献 将测定年轻SHR的血流自动调节。 的假设 肾血流的更有效的自动调节是由于过度的 肾小管肾小球反馈活性和/或更强的肌源性反应 将被调查。 血管活性激素/自育激素对 血管紧张素内在控制因子的相对强度 将被审查。 研究将测试肾脏过度的假设 血管反应性是由于对收缩系统的更大反应， 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PGE 2和PG 1 2与前列腺素E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。 PGE 2和PG 12的受体将在以下方面表征： 从年轻SHR分离的肾小球。肾小球血栓素的调节 受体将作为肾内浓度的函数进行评估， 血栓素 在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， 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类元激素系统 在人类原发性高血压的标准模型中。

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.