Abstract: TH-PO899
Mechanisms of High Salt Intake-Increased (Pro)renin Receptor Expression in the Nephron of Dahl Salt-Sensitive Rats
Session Information
- Molecular Mechanisms of CKD - I
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 1903 CKD (Non-Dialysis): Mechanisms
Authors
- Yamakoshi, Seiko, Nikko Medical Center, Dokkyo Medical University, Nikko, Japan
- Ito, Osamu, Tohoku Medical Pharmacetical University Faculty of Medicine, Sendai, Japan
Background
We recently reported that high-salt (HS) intake increased the (P)RR expression by 3-5 fold in several nephron segments of Sprague-Dawley rats (Peptides 63: 156-162, 2015). The present study examined the mechanisms of the HS-intake increased (P)RR expression in 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 xanthine oxidase (XO) inhibitor, febuxostat (Feb, 10mg/kg/day) or mineralocorticoid receptor (MR) antagonist, spironolactone (Spi, 100mg/kg/day). Additionally, deoxycorticosterone acetate (DOCA, 50mg/kg/week) administered to DS rats fed the NS diet for 4weeks. The (P)RR expression in the kidney sections and proximal tubules (PT) was examined by immunoblot and immunohistochemical analyses. XO activity in the CO was measured.
Results
HS intake increased the blood pressure, and Feb and Spi decreased the HS intake-increased blood pressure (p<0.01). HS intake increased the XO activity by 1.7 fold (p<0.01), and febuxostat blocked completely the activity. 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). Feb and Spi inhibited the HS intake-increased (P)RR expression in the cortex by 55% and 89%, respectively (p<0.001). Feb inhibited the HS intake-increased (P)RR expression in the PT by 69% (p<0.001), but Spi did not change the expression. Immunohistochemical analysis revealed that HS intake increased the (P)RR expression in the PT and distal tubules (DT) and that Feb inhibited the expression in the PT, and Spi inhibited the expression in the DT. In addition, DOCA increased the (P)RR expression in the cortex by 80% (p<0.001) and the DT, but not in the PT.
Conclusion
HS intake-increased (P)RR expression is enhanced in the PT and distal tubules 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.