Fasudil attenuates interstitial fibrosis in rat kidneys with unilateral ureteral obstruction.
This study was designed to investigate possible effects of the Rho-kinase inhibitor, fasudil, on the progression of renal failure in rats with unilateral ureteral obstruction. The renal failure markers monitored were the extent of renal interstitial fibrosis and that of macrophage infiltration. In kidneys with unilateral ureteral obstruction, interstitial fibrosis was observed, using Sirius-Red staining, on day 16 after unilateral ureteral obstruction. Macrophage infiltration was observed by immunohistochemistry, using the antibody, ED1. Interstitial fibrosis and macrophage infiltration were significantly attenuated in fasudil-treated animals. The migration of monocytes in vitro elicited by N-formyl-methionyl-leucyl-phenylalanine was potently inhibited by fasudil and its active metabolite, hydroxyfasudil. These results suggest that inhibition of Rho-kinase produces a reduction of macrophage infiltration and represents a new therapeutic strategy for renal fibrosis, a major factor in the progression to end-stage renal failure.
Satoh
Shin-ichi
S
Institute of Life Science Research, Asahi Kasei Corporation, 632-1, Mifuku, Ohito-Cho, Tagata-Gun, Shizuoka 410-2321, Japan. sato.sn@om.asahi-kasei.co.jp
Yamaguchi
Tamami
T
Hitomi
Asako
A
Sato
Norihiro
N
Shiraiwa
Kazumi
K
Ikegaki
Ichiro
I
Asano
Toshio
T
Shimokawa
Hiroaki
H
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005355:Fibrosis / Q000209:etiology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D047428:Protein Kinase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014517:Ureteral Obstruction / Q000150:complications*
D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; C431085:hydroxyfasudil; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049347:fasudil