Contribution of chymase-dependent angiotensin II formation to the progression of tubulointerstitial fibrosis in obstructed kidneys in hamsters

Yu Yan Fan, Akira Nishiyama, Yoshihide Fujisawa, Hiroyuki Kobori, Daisuke Nakano, Junji Matsuura, Naoki Hase, Hirofumi Hitomi, Hideyasu Kiyomoto, Hidenori Urata, Masakazu Kohno

研究成果: Article査読

24 被引用数 (Scopus)

抄録

Recent studies indicate a role of chymase in the regulation of angiotensin II (AngII) formation in cardiovascular and renal tissues. We investigated a possible contribution of chymase to AngII formation and to renal fibrosis in unilateral ureteral obstruction (UUO). Eight-week-old Syrian hamsters were subjected to UUO and treated with vehicle, the specific chymase inhibitor (CI) 4-[1-(4-methyl-benzo[b]thiophen-3-ylmethyl)-1H-benzimidazol-2-ylsulfanyl] -butyric acid (50 mg/kg, twice a day, p.o.), or the selective AT 1-receptor blocker olmesartan (10 mg/kg per day, p.o.) for 14 days. UUO-induced renal interstitial fibrosis was associated with increases in renal mRNA levels of α-smooth muscle actin (SMA), type I collagen, and transforming growth factor (TGF)-β. The UUO hamsters showed markedly higher AngII contents and increased AT1-receptor mRNA level in the obstructed kidney than sham-operated ones. In contrast, angiotensin-converting enzyme (ACE) protein expression was significantly lower in UUO hamsters. In UUO hamsters, treatment with CI or olmesartan significantly decreased AngII levels in renal tissue and mRNA levels of α-SMA, type I collagen, and TGF-β and ameliorated tubulointerstitial injury. On the other hand, neither CI nor olmesartan changed systolic blood pressure, renal ACE, and AT 1-receptor protein levels. These data suggest that chymase-dependent intrarenal AngII formation contributes to the pathogenesis of interstitial fibrosis in obstructed kidneys of hamsters.

本文言語English
ページ(範囲)82-90
ページ数9
ジャーナルJournal of Pharmacological Sciences
111
1
DOI
出版ステータスPublished - 2009

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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