A2298 Regulatory Mechanisms of (Pro)renin Receptor Expression in the Kidney of Dahl Salt-Sensitive Rats by High Salt Intake

Abstract

Objectives: The present study clarified the mechanisms of the HS-intake increased (P)RR expression in the kidney of Dahl-Salt sensitive (DS) rats. Methods: Male DS rats were fed a normal salt (NS) diet (0.6%NaCl) and a HS diet (8%NaCl) for 4weeks. A part of the rats fed the HS diet were treated orally with angiotensin II type1 receptor antagonist; candesartan (Can, 3 mg/kg/day), mineralocorticoid receptor (MR) antagonist; spironolactone (Spi, 100 mg/kg/day), or xanthine oxidase (XO) inhibitor; febuxostat (Feb, 10 mg/kg/day). Additionally, deoxycorticosterone acetate (DOCA, 50 mg/kg/week) administered to the rats fed the NS diet for 4weeks. The (P)RR expression in the kidney sections, proximal tubules (PT) and distal tubules (DT) was examined by immunoblot and immunohistochemical analyses. Results: HS intake increased the blood pressure, and Spi and Feb decreased the HS intake-increased blood pressure (p < 0.01). HS intake increased the (P)RR expression in the cortex by 22.6 fold (p < 0.001) and the PT by 4.9 fold (p < 0.01). Can, Spi and Feb inhibited the HS intake-increased (P)RR expression in the cortex by 32%, 89% and 55%, respectively (p < 0.001). Feb inhibited the HS intake-increased (P)RR expression in the PT by 69% (p < 0.001), but Can or Spi did not. Immunohistochemical analysis revealed that HS intake increased the (P)RR expression in the PT and DT. Spi inhibited the expression in the DT, whereas Feb inhibited the expression in the PT. In addition, DOCA increased the (P)RR expression in the cortex and DT, but not in the PT. Conclusion: HS intake-increased (P)RR expression is enhanced in the PT and DT of DS rats. The mechanisms of HS intake-increased (P)RR expression may be MR-dependent manner in the DT and XO-dependent manner in the PT.