Role of the juxtaglomerular apparatus in hypertension and progressive renal impairment

肾小球和肾小管的功能对体液和电解质的稳态很重要，因此对全身血压的调节也很重要。在这个项目中，我们采用了一种体外制剂，在控制的压力下灌注微解剖的传入（Af-Arts）或传出小动脉（Ef-Arts）。血管紧张素I.I型2受体（angiotensin I.I type 2 receptor, AT_2R）最近被克隆出来，但其功能作用尚不清楚。我们发现AT_2R的选择性激活导致Af-Art和Ef-Art的血管舒张。两小动脉的血管舒张程度相似。在Af-Art中，抑制一氧化氮合酶或环加氧酶均不影响扩张，然而，破坏内皮或抑制细胞色素P-450通路，特别是环氧二碳三烯酸（EETs）的合成，可消除扩张。这些结果表明，在Af-Art中，AT_2受体的激活可能通过细胞色素p -450途径引起内皮依赖性血管舒张，可能通过EETs。我们还研究了Ang II在肾脏内作用的异质性。我们发现腔内给药比腔外给药引起更强的血管收缩，仅在浅表而不是近髓心房动脉。此外，Ang ii诱导的血管收缩在浅表强于髓旁af - art。这种异质性对于肾脏维持体液和电解质的稳态可能是重要的。

Glomerular and tubular functions are important for homeostasis of body fluid and electrolytes, and hence for the regulation of systemic blood pressure. In this project we employed an in vitro preparation in which microdissected afferent (Af-Arts) or efferent arterioles (Ef-Arts) are perfused at a controlled pressure.Althought angiotensin I.I type 2 receptor (AT_2R) has recently been cloned, its functional role is not well understood. We found that selective activation of AT_2R causes vasodilation in the both the Af-Art and Ef-Art. The degree of vasodilation was simular in the two arterioles. In the Af-Art the dilation was unaffected by inhibiting either nitric oxide synthase or cycloxygenase, however, it was abolished by either disrupting the endothelium or inhibiting the cytochrome P-450 pathway, particularly the synthesis of epoxyeicosatrienoic acids (EETs). These results suggest that in the Af-Art activation of the AT_2 receptor may cause endothelium-dependent vasodilation via a cytochrome P-450pathway, possibly by EETs. We also studied heterogeneity of Ang II action within the kidney. We found that intraluminal administration of Ang II caused stronger vasoconstriction than extraluminal administration only in the superficial but not juxtamedullary Af-Arts. In addition, Ang II-induced vasoconstriction was stronger in the superficial than juxtamedullary Af-Arts. Such heterogeneities may be important in order for the kidney to maintain homeostasis of body fluid and electrolytes.