Regulation of Renal Microcirculation in Ang II-Induced Hypertension

在血管紧张素II诱导的高血压中，压力尿钠排泄设定点转移到更高的压力，可能是由于 肾血管阻力和Na+重吸收增加。传入（Af-Art）和传出小动脉 （Ef-Art）占大多数肾血管阻力;它们控制GFR和管周压，从而影响肾血管阻力。 功能Af-Art抵抗力受有利于血管收缩的因素和那些 有利于血管扩张。我们的初步数据表明，增加Na+输送到连接小管， (CNT)会导致动脉扩张这种作用在这里被称为连接小管肾小球反馈（CTGF） 并且是有利于扩张的生理因素。研究CTGF的作用机制，同时避免其影响 我们建议使用我们开发的一种技术，该技术包括体外灌注一种 显微解剖的Af-Art和粘附的CNT。CNT不仅在Na+吸收和K+吸收中起重要作用， 分泌，而且还合成激肽释放酶，肾素，NO和类花生酸;然而，这些因素的作用， CTGF未知。我们建议测试C7 GF促进Af-Art扩张的一般假设 并因此拮抗血管收缩刺激物如Ang II和TGF。CTGF是由 花生四烯酸代谢产物。在血管紧张素II诱导的高血压期间，CTGF由于血管紧张素II诱导的高血压而增强。 联合作用的血管紧张素Ⅱ，O2'和醛固酮对Na* 转运;然而，在af-art这种刺激， 内皮源性收缩因子和CNT中NO的增加使其变钝。这一假设 将在以下测试中进行测试

In Ang ll-induced hypertension, the pressure natriuresis set point is shifted to a higher pressure, probably due to an increase in renal vascular resistance and Na+ reabsorption. The afferent (Af-Art) and efferent arterioles (Ef-Art) account for most renal vascular resistance; they control GFR and peritubular pressure, and thus renal function. Af-Art resistance is regulated by a balance between factors favoring vasoconstriction and those favoring vasodilatation. Our preliminary data indicate that increased Na+ delivery to the connecting tubule (CNT) causes Af-Art dilatation. This effect will here be called connecting tubule glomerular feedback (CTGF) and is a physiological factor favoring dilatation. To study the mechanism of CTGF while avoiding the influence of systemic factors, we propose to use a technique developed by us that consists of in vitro perfusion of a microdissected Af-Art and adherent CNT. The CNT not only plays an important role in Na+ absorption and K+ excretion but also synthesizes kallikrein, renin, NO and eicosanoids; however, the role of these factors in CTGF is unknown. We propose to test the general hypothesis that C7GF promotes dilatation of the Af-Art and thus antagonizes vasoconstrictor stimuli such as Ang II and TGF. CTGF is mediated by arachidonic acid metabolites. During Ang ll-induced hypertension, CTGF is enhanced due to the combined effects of Ang II, O2'andaldosterone on Na* transport; however, in theAf-Art this stimulation is bluntedby endothelium-derived constricting factors and by increased NO in the CNT. This hypothesis will be tested in the following