title: Chronic cadmium treatment promotes oxidative stress and endothelial damage in isolated rat aorta.
abstract: Cadmium is a highly toxic metal that is present in phosphate fertilizers, and the incidence of cadmium poisoning in the general population has increased, mainly due to cigarette smoking. Once absorbed, cadmium accumulates in the tissues, causing harmful effects including high blood pressure, endothelial damage and oxidative stress. Oxidative stress is known to efficiently produce oxidized low-density lipoprotein and consequently atherosclerosis, mainly in the aorta. However, the mechanisms through which endothelial damage is induced by cadmium have not been elucidated. Thus, the aim of this study was to investigate the effects of this metal in the isolated aorta and the possible role of oxidative stress. Rats received 100 mg.L(-1) cadmium chloride (CdCl2) in the drinking water or distilled water alone for four weeks. The pressor effect of cadmium was followed throughout the exposure period by tail plethysmography. At the end of the fourth week, the blood cadmium content was established, and the vascular reactivity of the isolated aorta to phenylephrine, acetylcholine and sodium nitroprusside was analyzed in the context of endothelium denudation and incubation with L-NAME, apocynin, losartan, enalapril, superoxide dismutase (SOD) or catalase. We observed an increased response to phenylephrine in cadmium-treated rats. This increase was abolished by catalase and SOD incubation. Apocynin treatment reduced the phenylephrine response in both treatment groups, but its effect was greater in cadmium-treated rats, and NOX2 expression was greater in the cadmium group. These results suggested that cadmium in blood concentrations similar to those found in occupationally exposed populations is able to stimulate NOX2 expression, contributing to oxidative stress and reducing NO bioavailability, despite enhanced eNOS expression. These findings suggest that cadmium exposure promotes endothelial damage that might contribute to inflammation, vascular injury and the development of atherosclerosis.
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, Espírito Santo, Brazil. camilaalmenaracp@gmail.com
authors.forename: Camila C P
authors.initials: CC
authors.lastname: Almenara
authors.forename: Gilson B
authors.initials: GB
authors.lastname: Broseghini-Filho
authors.forename: Marcus V A
authors.initials: MV
authors.lastname: Vescovi
authors.forename: Jhuli K
authors.initials: JK
authors.lastname: Angeli
authors.forename: Thaís de O
authors.initials: Tde O
authors.lastname: Faria
authors.forename: Ivanita
authors.initials: I
authors.lastname: Stefanon
authors.forename: Dalton V
authors.initials: DV
authors.lastname: Vassallo
authors.forename: Alessandra S
authors.initials: AS
authors.lastname: Padilha
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002104:Cadmium / Q000097:blood / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D003720:Densitometry; D004656:Enalapril / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D013599:Systole / Q000187:drug effects
chemical_list: D000098:Acetophenones; D002104:Cadmium; D009599:Nitroprusside; D010656:Phenylephrine; D004656:Enalapril; C056165:acetovanillone; D002374:Catalase; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D019808:Losartan; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester