Role of the juxtaglomerular apparatus in hypertension and progressive renal impairment

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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.