Regulation of Renal Microcirculation in Ang II-Induced Hypertension

在血管紧张性高血压中，压力钠尿设定点向更高的压力移动，这可能是由于 增加肾血管阻力和钠重吸收。传入(Af-Art)和传出小动脉 (EF-ART)解释了大多数肾血管阻力；它们控制GFR和管周压力，从而控制肾脏 功能。房颤-ART抵抗是由有利于血管收缩的因素和那些 有利于血管扩张的。我们的初步数据显示，钠向连接小管的输送增加 (CNT)导致Af-Art扩张。这种效应在这里被称为连接小管肾小球反馈(CTGF)。 是一种有利于扩张的生理因素。在避免影响的同时研究CTGF的作用机理 我们建议使用我们开发的一种技术，该技术包括体外灌流一种 显微解剖Af-Art和贴壁CNT。碳纳米管不仅在钠和钾的吸收中起重要作用 排泄还合成激肽释放酶、肾素、一氧化氮和二十烷类化合物；然而，这些因素在 CTGF尚不清楚。我们建议检验C7GF促进房颤-ART扩张的普遍假设 从而拮抗血管收缩刺激，如血管紧张素II和转化生长因子。CTGF通过以下方式进行调节 花生四烯酸代谢物。在AngⅡ诱导性高血压期间，CTGF由于 Ang II、O2‘和醛固酮联合作用对Na~*转运的影响 被内皮衍生的收缩因子和CNT中增加的NO所钝化。这一假设 将在以下方面进行测试

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