Up-regulation of intrarenal renin-agiotensin system contributes to renal damage in high-salt induced hypertension rats

Kidney Blood Press Res. 2014;39(6):526-35. doi: 10.1159/000368463. Epub 2014 Nov 29.

Abstract

Background/aims: To investigate the change of intrarenal renin-agiotensin system (RAS) and its role in high-salt induced hypertension.

Methods: Wistar rats were divided into normal-salt (NS), high-salt diet (HS) and high-salt diet with Losartan group (HS+L), for 6 weeks. Systolic blood pressure (SBP) was monitored. Blood and urine samples were collected every 2 weeks. Angiotensinogen (AGT) was measured by ELISA. AGT mRNA and protein were measured by real-time PCR and immunohistochemistry. Renin activity and angiotensin II (Ang II) were measured by radioimmunoassay.

Results: HS versus NS group, SBP increased from 2(nd) week (P<0.05), urinary protein increased at 6(th) week (P<0.05). Although plasma renin, AGT and Ang II had no significant changes (P>0.05), renal cortex renin, AGT, and Ang II increased significantly in HS (P<0.05). In HS+L, Losartan failed to reduce SBP (P>0.05) but abolished the increase of proteinuria (P<0.01), renal cortex renin, AGT, Ang II and urinary AGT reduced (P<0.05) while plasma renin, AGT and Ang II enhanced (P<0.05) when compared with HS. Urinary AGT was positively correlated with renal AGT (r=0.592, P <0.01) and Ang II (r=0.726, P <0.01).

Conclusion: Inappropriate response of the renal RAS to a high salt diet may contribute to hypertension and renal damage, and urinary AGT could reflect intrarenal RAS activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / blood
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Angiotensinogen / metabolism
  • Animals
  • Diet
  • Hypertension, Renal / chemically induced*
  • Hypertension, Renal / pathology*
  • Kidney / pathology*
  • Losartan / therapeutic use
  • Male
  • Proteinuria / chemically induced
  • Proteinuria / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar
  • Renin / blood
  • Renin-Angiotensin System / genetics*
  • Sodium Chloride, Dietary / adverse effects*
  • Up-Regulation

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • RNA, Messenger
  • Sodium Chloride, Dietary
  • Angiotensinogen
  • Angiotensin II
  • Renin
  • Losartan