Role of renin-angiotensin system and nuclear factor-kappaB in the obstructed kidney of rats with unilateral ureteral obstruction.
The present study was conducted to elucidate the role of oxidative stress and nuclear factor-kappaB (NF-kappaB) in the beneficial effects of angiotensin receptor blockade on obstructive nephropathy. Unilateral ureteral occlusion in rats elicited tubulo-interstitial fibrosis with concomitant macrophage infiltration and increased expression of monocyte chemoattractant protein-1. These changes were accompanied by an induction of renal cortical lipid peroxidation and activation of NF-kappaB. Both an AT(1) antagonist, candesartan, and a NF-kappaB inhibitor, pyrrolidine dithiocarbamate, markedly attenuated these changes and to a similar extent. These results suggest that the beneficial effects of angiotensin blockade are mediated by the inhibition of oxidative stress and subsequent NF-kappaB activation in obstructive nephropathy.
Nakatani
Tatsuya
T
Department of Urology, Osaka City University, Japan.
Tamada
Satoshi
S
Asai
Toshihiro
T
Iwai
Yoshihito
Y
Kim
Taku
T
Tsujino
Takashi
T
Kumata
Norihiko
N
Uchida
Junji
J
Tashiro
Koichiro
K
Kuwabara
Nobuyuki
N
Komiya
Toshiyuki
T
Sumi
Tomohiko
T
Okamura
Mikio
M
Miura
Katsuyuki
K
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D005355:Fibrosis; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012084:Renin-Angiotensin System; D013777:Tetrazoles / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
D057911:Angiotensin Receptor Antagonists; D000975:Antioxidants; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D016328:NF-kappa B; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D013777:Tetrazoles; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; C081643:candesartan