title: Zinc-Excess Intake Causes the Deterioration of Renal Function Accompanied by an Elevation in Systemic Blood Pressure Primarily Through Superoxide Radical-Induced Oxidative Stress.
abstract: Using rats fed 22 g/d of a control diet containing 0.005% zinc (Zn) or 2 Zn-excess diets containing 0.05% or 0.2% Zn for 4 weeks, we examined the mechanisms involved in the deterioration of renal function induced by Zn-excess intake. An increase in Zn intake elevated mean blood pressure (BP) and reduced renal blood flow (RBF) and inulin clearance in a dose-dependent manner. This decline in inulin clearance may be derived from a fall in RBF. Administration of the nitric oxide (NO) synthase inhibitor, Nω-nitro-l-arginine methyl ester, markedly increased mean BP and significantly decreased RBF in the 3 groups of rats. Administration of the exogenous superoxide radical (OO-) scavenger, tempol, significantly decreased mean BP and substantially increased RBF in all groups of rats. These observations suggest that both an elevation in systemic BP and a reduction in RBF seen in the 2 Zn-excess diet groups result from a decrease in the action of the vasodilator, NO, through the formation of peroxynitrite based on the nonenzymatic reaction of NO and increased OO-Indeed, the activity of the endogenous OO-scavenger, copper/Zn-superoxide dismutase, was significantly reduced in the vessel wall of rats fed 2 Zn-excess diets versus a control diet. 8-Hydroxy-2'-deoxyguanosine formation caused by OO-generation was notably elevated in the kidneys of rats fed 2 Zn-excess diets relatively to rats fed a control diet. Thus, Zn-excess intake leads to the aggravation of renal function concomitantly with an increase in systemic BP predominantly through the oxidative stress caused by OO<sup/>.
authors.affiliation: Department of Public Health and Environmental Medicine, Faculty of Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan hryanagisawa@jikei.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yanagisawa
authors.affiliation: Community Health Science Center, Saitama Medical University, Moroyama, Iruma-gun, Saitama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: School of Medical Technology and Health, Saitama Medical University, Hidaka City, Saitama, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nodera
authors.affiliation: School of Medical Technology and Health, Saitama Medical University, Hidaka City, Saitama, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Miyajima
authors.affiliation: Department of Public Health and Environmental Medicine, Faculty of Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Public Health and Environmental Medicine, Faculty of Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Kido
authors.affiliation: Department of Public Health and Environmental Medicine, Faculty of Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
authors.forename: Machi
authors.initials: M
authors.lastname: Suka
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001013:Aorta, Thoracic; D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D019587:Dietary Supplements / Q000506:poisoning*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000009:adverse effects; D016166:Free Radical Scavengers / Q000627:therapeutic use; D000075322:Heavy Metal Poisoning / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006978:Hypertension, Renovascular / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D007444:Inulin / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D000072105:Superoxide Dismutase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015032:Zinc / Q000506:poisoning*
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D007444:Inulin; D019001:Nitric Oxide Synthase; C000606292:Sod1 protein, rat; D000072105:Superoxide Dismutase-1; D003849:Deoxyguanosine; D015032:Zinc
keywords: blood pressure; oxidative stress; renal function; zinc