title: Attenuation of hypertension and renal damage in renovascular hypertensive rats by iron restriction.
abstract: Iron is a catalyst in the formation of reactive oxygen species. Oxidative stress is associated with the pathogenesis of both human and experimental animal models of renovascular hypertension. We hypothesized that iron is involved in the pathogenesis of renovascular hypertension and that iron restriction may affect the pathogenesis of renovascular hypertension via the inhibition of oxidative stress. Herein, we investigated the effect of iron restriction on hypertension and renal damage in a rat model of two-kidney one-clip (2K1C) renovascular hypertension. Renovascular hypertension was induced by 2K1C in male Sprague-Dawley rats. At the day of clipping, 2K1C rats were divided into untreated (2K1C) and dietary iron-restricted groups (2K1C+IR). The 2K1C rats showed hypertension after the day of clipping, whereas dietary iron restriction attenuated the development of hypertension. Vascular hypertrophy and the increased fibrotic area were suppressed in the 2K1C+IR group. The clipped kidney developed renal atrophy in both the 2K1C and 2K1C+IR groups after clipping. However, the unclipped kidney showed renal hypertrophy in the 2K1C and 2K1C+IR groups, and the extent was less in the 2K1C+IR group. The 2K1C rats exhibited glomerulosclerosis and tubulointerstitial fibrosis in the unclipped kidney, whereas these changes were attenuated by an iron-restricted diet. Importantly, proteinuria was decreased in the 2K1C+IR group, along with decreased urinary 8-hydroxy-2'-deoxyguanosine excretion and superoxide production of the unclipped kidney. Moreover, the expression of nuclear mineralocorticoid receptor in the unclipped kidney of the 2K1C rats was attenuated by iron restriction. These data indicate a novel effect of iron restriction on hypertension and renal damage in renovascular hypertension.
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Oboshi
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sawada
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Iwasaku
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okuhara
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Akiyo
authors.initials: A
authors.lastname: Eguchi
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirotani
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Mano
authors.affiliation: Department of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsujino
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Masuyama
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology; D006978:Hypertension, Renovascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D000090463:Iron Deficiencies; D019266:Iron, Dietary; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D019266:Iron, Dietary; D018161:Receptors, Mineralocorticoid; D013481:Superoxides; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine