Abstract-In Sprague-Dawley rats, renal angiotensin (Ang) type 2 receptors (AT 2 Rs) mediate natriuresis in response to renal interstitial (RI) D 1 -like receptor stimulation or RI Ang III infusion. After D 1 -like receptor activation, apical membrane (AM) but not total renal proximal tubule cell AT 2 R expression is increased, suggesting that AM AT 2 R translocation may be important for natriuresis. Key Words: sodium Ⅲ natriuresis Ⅲ angiotensin III Ⅲ AT 2 receptor Ⅲ AT 1 receptor Ⅲ translocation T he renin-angiotensin system is a coordinated hormonal cascade of crucial importance in cardiovascular and renal function. In recent years, an emphasis has been placed on delineating the role of the intrarenal renin-angiotensin system in the regulation of blood pressure (BP) 1,2 and sodium (Na ϩ ) balance. [3][4][5] The majority of the effects of the intrarenal reninangiotensin system are mediated by 2 angiotensin receptors, angiotensin (Ang) type 1 (AT 1 R) and Ang II type II (AT 2 R). Renal AT 1 Rs, as a consequence of their antinatriuretic actions, are required for the development of Ang II-dependent hypertension, because the presence of systemic extrarenal AT 1 Rs alone is not sufficient to sustain hypertensive responses to Ang II infusion. 1 Furthermore, AT 1 Rs in renal proximal tubule cells (RPTCs), as opposed to other sites along the nephron, are primarily responsible for this response. 6 In Sprague-Dawley rats, renal AT 2 Rs have been reported to mediate natriuresis in response to renal interstitial (RI) AT 1 R blockade or Ang III infusion. 3 Inhibition of the conversion of Ang II to Ang III in the kidney abolishes natriuresis mediated by renal AT 2 Rs, indicating that Ang III is the preferred agonist of this response. 4 Thus, RPTC AT 1 Rs and AT 2 Rs are major determinants of BP and Na ϩ responses in normal and hypertensive animals.The intrarenaldopaminergic system also plays an important role in the regulation of Na ϩ balance. Dopamine, synthesized by the RPTCs, mediates diuresis and natriuresis via D 1 -like receptor (D 1 R) activation. 7,8 A physiological interaction between the intrarenal renin-angiotensin system and dopaminergic systems has been reported in normal Sprague-Dawley rats. In response to a high-salt diet, RI D 1 R activation with fenoldapam results in natriuresis and diuresis that is abolished by selective pharmacological inhibition of renal AT 2 Rs with PD-123319 (PD). 9 Furthermore, fenoldapam-induced natriuresis is accompanied by an increase in apical plasma membrane (AM) but not total RPTC AT 2 R expression, as quantified by Western blot analysis. 9 Thus, D 1 R-mediated natriuresis depends on functional renal AT 2 Rs, and one of the mechanisms involves RPTC AT 2 R translocation.Spontaneously hypertensive rats (SHRs) develop hypertension as they age and are widely used as a model to study the development and maintenance of human primary (essential) hypertension. 10 Before the onset of hypertension, SHRs
