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

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