Abstract-We explored the effects of direct renal interstitial stimulation of dopamine D 1 -like receptors with fenoldopam, a selective D 1 -like receptor agonist, on renal sodium excretion and angiotensin type-2 (AT 2 ) receptor expression and cellular distribution in rats on a high-sodium intake. In contrast to vehicle-infused rats, sodium excretion increased in fenoldopam-infused rats during each of three 1-hour experimental periods (Ͻ0.001 Key Words: angiotensin Ⅲ dopamine Ⅲ receptors Ⅲ sodium excretion Ⅲ natriuresis Ⅲ receptor trafficking Ⅲ kidney T he kidney is endowed with 2 local hormonal systems that play a major role in the regulation of sodium (Na ϩ ) transport across the renal proximal tubule (RPT): the reninangiotensin system and the dopaminergic system. In vitro studies show that angiotensin II (Ang II), the major effector peptide of the renin-angiotensin system, acts at angiotensin type-1 (AT 1 ) receptors on RPT cell membranes to increase Na ϩ transport across the cell from the lumen into the interstitial space and peritubular capillaries by stimulating Na ϩ -hydrogen (H ϩ ) exchanger-3 (NHE-3) and Na ϩ ,K ϩ -ATPase activities, respectively. 1 On the other hand, dopamine (DA), synthesized in and secreted from RPT cells, activates D 1 -like receptors (D 1 and D 5 receptor subtypes) on RPT cells to inhibit Na ϩ reabsorption by inhibiting NHE-3 and Na ϩ ,K ϩ -ATPase activities. 2,3 Although these 2 hormonal systems act in opposite directions on RPT Na ϩ transport in vitro, little is known regarding the physiological interactions of intrarenal Ang II and DA in the control of Na ϩ excretion in vivo. Approximately 50% of basal Na ϩ excretion is mediated by the paracrine action of renal DA on RPT D 1 -like receptors. 4,5 However, the mechanisms of receptor interaction that govern DA-induced natriuresis are incompletely understood. DA downregulates AT 1 receptors (AT 1 Rs) in the RPT. 6 However, Ang II binds to angiotensin type-2 (AT 2 ) receptors (AT 2 Rs), as well as AT 1 Rs, and the effects of DA on AT 2 Rs are unknown.AT 2 Rs are expressed in the RPT but have a low degree of renal expression compared with that of AT 1 Rs. 7 The present study explores the direct renal interstitial (RI) stimulation of D 1 receptors with fenoldopam, a selective D 1 -like receptor agonist, and its effects on renal Na ϩ excretion and AT 2 R expression in the rat. We demonstrate that natriuresis induced by stimulation of renal D 1 -like receptors requires AT 2 R expression and recruitment to the RPT plasma membrane. In the presence of AT 2 R inhibition, D 1 -like receptor stimulation is not able to induce renal Na ϩ excretion.

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