REGULATION OF RENAL VASCULAR CELLS IN HYPERTENSION

高血压肾血管细胞的调节

基本信息

批准号：
6030679
负责人：
CRAIG H GELBAND
金额：
$ 8.98万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-07-01 至 2000-06-30
项目状态：
已结题

项目摘要

The relationship between renal blood flow and glomerular filtration rate is well established. A decrease, in renal blood flow lowers glomerular filtration rate triggering water retention and increases in extracellular fluid volume and venous return. Following the Frank-Starling mechanism, increases in cardiac output and arterial pressure are observed. If both renal blood flow and glomerular filtration rate remain suppressed, the initial steps in the development of hypertension have taken place. In spite of the vast literature discussing renal circulation, the mechanisms underlying renal vascular disorders in various forms of hypertension are poorly understood. Since changes in renal blood flow have been implicated in certain vascular disorders, including hypertension and renal vasospasm, this research will help to fill the existing gap of knowledge regarding the relationship between ion channel regulation and vascular reactivity in the renal vasculature. This proposal seeks to obtain new information about the membrane abnormalities associated with renal vascular smooth muscle cells in rat models of genetic and nongenetic hypertension. The general hypothesis for this application is that ion channel function is altered in hypertension and that intracellular modulators, such as Ca2+, may play a role in altered regulation in the hypertensive models. Single smooth muscle cells will be enzymatically dispersed from Wistar-Kyoto (WKY), Sprague-Dawley (SD), Spontaneously Hypertensive (SHR), and DOCA (deoxycorticosterone acetate) hypertensive rat interlobar/arcuate artery of the kidney and the patch clamp technique will be utilized to characterize the properties of Ca2+ and K+ channels in these cells. Determining the pharmacological and biophysical properties of these ionic conductances will serve as a foundation to show the usefulness of isolated SHR and DOCA interlobar/arcuate arterial smooth muscle cells, when compared to control cells from SD and WKY rats, as a model of hypertension for studies involving ion channel regulation by various physiological stimuli. A number of circulating hormones, for example angiotensin II and arginine vasopressin produce significant vasoconstriction and changes in the levels of intracellular Ca2+ in renal arterial smooth muscle. The effects of these agents on membrane potential and whole-cell currents will be quantified. Simultaneously, changes in intracellular [Ca2+] in normo- and hypertensive cells will be measured with a PMT-based indo-1 microfluorometry system. The results provided from these studies should increase our knowledge of the mechanism of hormonal modulation of vascular tone in a clinically relevant tissue, the renal vascular bed and its role in the etiology of hypertension.

肾血流与肾小球滤过率之间的关系已经建立了。减少，在肾血流中降低肾小球过滤率触发水分retention留并增加细胞外流体体积和静脉回流。遵循坦率的宣传机制，观察到心输出量和动脉压的增加。如果这两个肾血流和肾小球滤过率仍然受到抑制，高血压发展的初始步骤已经发生。在大量文献讨论了肾脏循环，这是机制各种形式的高血压的潜在肾脏血管疾病是理解不佳。由于肾脏血流的变化已涉及在某些血管疾病中，包括高血压和肾血管痉挛，这项研究将有助于填补有关有关的现有知识空白离子通道调控与血管反应之间的关系肾脏脉管系统。该建议旨在获取有关的新信息与肾血管平滑肌相关的膜异常遗传和非遗传性高血压大鼠模型中的细胞。将军该应用的假设是离子通道函数在高血压和细胞内调节剂（例如Ca2+）可能会发挥作用在高血压模型中调节改变中的作用。单个平滑肌肉细胞将从Wistar-Kyoto（WKY）中分散为酶细胞， Sprague-Dawley（SD），自发性高血压（SHR）和DOCA （乙酸乙酸乙酸乙酸甘发产）高血压大鼠间盘间/弧形动脉肾脏和斑块夹技术将用于表征这些细胞中Ca2+和K+通道的性质。确定这些离子的药理和生物物理特性电导将作为展示孤立有用性的基础 SHR和DOCA Interlobar/弧形平滑肌细胞，当与SD和WKY大鼠的对照细胞相比，作为高血压的模型用于涉及各种生理的离子通道调节的研究刺激。许多循环激素，例如血管紧张素II和精氨酸加压素产生显着的血管收缩和变化肾动脉平滑肌中细胞内Ca2+的水平。这这些药物对膜电位和全细胞电流的影响被量化。同时，正常的细胞内[Ca2+]的变化和高血压细胞将通过基于PMT的Indo-1进行测量微氟计量系统。这些研究提供的结果应增加我们对血管激素调节机制的了解临床相关的组织，肾血管床及其作用中的音调在高血压的病因中。