title: Increased renal iron accumulation in hypertensive nephropathy of salt-loaded hypertensive rats.
abstract: Although iron is reported to be associated with the pathogenesis of chronic kidney disease, it is unknown whether iron participates in the pathophysiology of nephrosclerosis. Here, we investigate whether iron is involved in the development of hypertensive nephropathy and the effects of iron restriction on nephrosclerosis in salt- loaded stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were given either a normal or high-salt diet for 8 weeks. Another subset of SHRSP were fed a high-salt with iron-restricted diet. SHRSP given a high-salt diet developed severe hypertension and nephrosclerosis. As a result, survival rate was decreased after 8 weeks diet. Importantly, massive iron accumulation and increased iron content were observed in the kidneys of salt-loaded SHRSP, along with increased superoxide production, urinary 8-Hydroxy-2'-deoxyguanosine excretion, and urinary iron excretion; however, these changes were markedly attenuated by iron restriction. Of interest, expression of cellular iron transport proteins, transferrin receptor 1 and divalent metal transporter 1, was increased in the tubules of salt-loaded SHRSP. Notably, iron restriction attenuated the development of severe hypertension and nephrosclerosis, thereby improving survival rate in salt-loaded SHRSP. Taken together, these results suggest a novel mechanism by which iron plays a role in the development of hypertensive nephropathy and establish the effects of iron restriction on salt-induced nephrosclerosis.
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Naito
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sawada
authors.forename: Makiko
authors.initials: M
authors.lastname: Oboshi
authors.forename: Aya
authors.initials: A
authors.lastname: Fujii
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirotani
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Iwasaku
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okuhara
authors.forename: Akiyo
authors.initials: A
authors.lastname: Eguchi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Morisawa
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Ohyanagi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsujino
authors.forename: Tohru
authors.initials: T
authors.lastname: Masuyama
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D027682:Cation Transport Proteins / Q000378:metabolism; D006977:Hypertension, Renal / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007501:Iron / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009393:Nephritis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009400:Nephrosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011990:Receptors, Transferrin / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D007501:Iron; D011990:Receptors, Transferrin; D017673:Sodium Chloride, Dietary; D000099236:Solute Carrier Family 11, Member 2; C545564:Tfrc protein, rat