title: Role of renin-angiotensin system and nuclear factor-kappaB in the obstructed kidney of rats with unilateral ureteral obstruction.
abstract: 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.
authors.affiliation: Department of Urology, Osaka City University, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nakatani
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tamada
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Asai
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Iwai
authors.forename: Taku
authors.initials: T
authors.lastname: Kim
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsujino
authors.forename: Norihiko
authors.initials: N
authors.lastname: Kumata
authors.forename: Junji
authors.initials: J
authors.lastname: Uchida
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tashiro
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kuwabara
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Komiya
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Sumi
authors.forename: Mikio
authors.initials: M
authors.lastname: Okamura
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Miura
mesh_terms: 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*
chemical_list: 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