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Complete disruption of all nitric oxide synthase genes causes markedly accelerated renal lesion formation following unilateral ureteral obstruction in mice in vivo
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نویسنده
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morisada n. ,nomura m. ,nishii h. ,furuno y. ,sakanashi m. ,sabanai k. ,toyohira y. ,ueno s. ,watanabe s. ,tamura m. ,matsumoto t. ,tanimoto a. ,sasaguri y. ,shimokawa h. ,kusuhara k. ,yanagihara n. ,shirahata a. ,tsutsui m.
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منبع
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journal of pharmacological sciences - 2010 - دوره : 114 - شماره : 4 - صفحه:379 -389
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چکیده
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The role of nitric oxide (no) derived from all three no synthases (noss) in renal lesion formation remains to be fully elucidated. we addressed this point in mice lacking all noss. renal injury was induced by unilateral ureteral obstruction (uuo). uuo caused significant renal lesion formation (tubular apoptosis,interstitial fibrosis,and glomerulosclerosis) in wild-type,singly,and triply nos-/- mice. however,the extents of renal lesion formation were markedly and most accelerated in the triply nos-/- genotype. uuo also elicited the infiltration of inflammatory macrophages,up-regulation of transforming growth factor (tgf)-β1,and induction of epithelial mesenchymal transition (emt) in all of the genotypes; however,the extents were again largest by far in the triply nos-/- genotype. importantly,long-term treatment with the angiotensin ii type 1 (at 1)-receptor blocker olmesartan significantly prevented the exacerbation of those renal structural changes after uuo in the triply nos -/- genotype,along with amelioration of the macrophage infiltration,tgf-β1 levels,and emt. these results provide the first evidence that the complete disruption of all nos genes results in markedly accelerated renal lesion formation in response to uuo in mice in vivo through the at 1-receptor pathway,demonstrating the critical renoprotective role of all noss-derived no against pathological renal remodeling. ©2010 the japanese pharmacological society.
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کلیدواژه
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Angiotensin; Knockout mouse; Nitric oxide synthase; Renal remodeling; Unilateral ureteral obstruction
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آدرس
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department of pediatrics,school of medicine,university of occupational and environmental health,kitakyushu 807-8555, Japan, department of urology,school of medicine,university of occupational and environmental health,kitakyushu 807-8555, Japan, department of urology,school of medicine,university of occupational and environmental health,kitakyushu 807-8555, Japan, department of pharmacology,school of medicine,university of occupational and environmental health,kitakyushu 807-8555, Japan, department of pharmacology,graduate school of medicine,university of the ryukyus,okinawa 903-0215, Japan, department of pharmacology,school of medicine,university of occupational and environmental health,kitakyushu 807-8555, Japan, department of pharmacology,school of medicine,university of occupational and environmental health,kitakyushu 807-8555, Japan, department of pharmacology,school of medicine,university of occupational and environmental health,kitakyushu 807-8555, Japan, department of pediatrics,school of medicine,university of occupational and environmental health,kitakyushu 807-8555, Japan, department of internal medicine,school of medicine,university of occupational and environmental health,kitakyushu 807-8555, Japan, department of urology,school of medicine,university of occupational and environmental health,kitakyushu 807-8555, Japan, department of pathology,kagoshima university,graduate school of medical and dental sciences,kagoshima 890-8544, Japan, department of pathology,school of medicine,university of occupational and environmental health,kitakyushu 807-8555, Japan, department of cardiovascular medicine,tohoku university,graduate school of medicine,sendai 980-8574, Japan, department of pediatrics,school of medicine,university of occupational and environmental health,kitakyushu 807-8555, Japan, department of pharmacology,school of medicine,university of occupational and environmental health,kitakyushu 807-8555, Japan, department of pediatrics,school of medicine,university of occupational and environmental health,kitakyushu 807-8555, Japan, department of pharmacology,school of medicine,university of occupational and environmental health,kitakyushu 807-8555,japan,department of pharmacology,graduate school of medicine,university of the ryukyus,okinawa 903-0215, Japan
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Authors
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