Effect of amlodipine on mouse renal interstitial fibrosis

Eur J Pharmacol. 2016 Jun 5;780:136-41. doi: 10.1016/j.ejphar.2016.03.041. Epub 2016 Mar 28.

Abstract

Unilateral ureteral obstruction (UUO) is a well-established method to study interstitial fibrosis of the kidney. In this study, we investigated the effects of a calcium channel blocker, amlodipine, on UUO-induced renal interstitial fibrosis in mice. UUO significantly increased the fibrotic area in the obstructed kidney, but this change was inhibited by amlodipine (6.7mg/kg/day in drinking water). mRNA expression of heat shock protein (HSP) 47 and type IV collagen was increased in the kidneys of UUO mice. Amlodipine reduced the expression of both HSP47 and type IV collagen mRNAs. Phosphorylation of c-jun-N-terminal kinase (JNK) was significantly increased by UUO, but the change was inhibited by amlodipine. Collectively, these results suggest that amlodipine may inhibit the expression of HSP47 and type IV collagen by reducing phosphorylation of JNK and ameliorating the renal interstitial fibrosis induced by UUO.

Keywords: Amlodipine; Fibrosis; Heat shock protein 47; Type IV collagen; Unilateral ureteral obstruction; c-jun-N-terminal kinase (JNK).

MeSH terms

  • Amlodipine / pharmacology*
  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Fibrosis
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice
  • Phosphorylation / drug effects
  • Ureteral Obstruction / complications

Substances

  • Calcium Channel Blockers
  • Amlodipine