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.

Arsenic, Reactive Oxygen, and Endothelial Dysfunction

“…Clarification of these mechanisms will have potentially far-reaching implications in relation to the understanding of iatrogenic effects of arsenic during treatment of acute promyelocytic leukemia, and also the initiation and progression of hypertension and vascular disease due to environmental exposure. Notably, heavy metal environmental contaminants such as mercury, cadmium, and chromium are all associated with endothelial dysfunction and cardiovascular risk through mechanisms involving oxidative stress and Nox2 (Wiggers et al, 2008;Almenara et al, 2013;Kukongviriyapan et al, 2014).…”

Endothelial dysfunction in subjects with chronic cadmium exposure

“…Cd altered endothelial cell integrity by disruption of cadherin-cadherin bonds, resulting in the increased permeability of vascular endothelium (Pearson et al, 2003). Cd exposure promoted NADPH oxidase expression in rat aorta, inducing oxidative stress in endothelial cells and impairing relaxation response to acetylcholine (Almenara et al, 2013). Oxidation of tetrahydrobiopterin (BH 4 ), a NOS cofactor, to BH 2 uncouples eNOS (Vásquez-Vivar et al, 2003), leading to production of superoxide.…”

“…Cd induced hypertension in rats, which involved oxidative stress and suppression of eNOS expression in blood vessels leading to impaired acetylcholineinduced vasorelaxation (Yoopan et al, 2008;Donpunha et al, 2011). Rats treated with Cd had increased response to vasopressor phenylephrine, and increased expression of NADPH oxidase in endothelial cells (Almenara et al, 2013). However, the change in endothelial function markers by Cd had never been reported in human.…”

The Association of Blood Concentrations of Healvy Metals and Blood Pressure in Residents Living Near Janghang Copper Smelter in Korea

“…Sang-Yong Eom 1) , Dong-Hyuk Yim 1) , Sun-In Moon 1) , Bolormaa Ochirpurev 1) , Young-Sook Choi 2) , Choong-Hee Park 3) , Guen-Bae Kim 3) , Seung-Do Yu 3) , Byung-Sun Choi 4) , Jung-Duck Park 4) , Yong-Dae Kim 1) , Heon Kim Table 5. General linear models for systolic and diastolic blood pressure in female subjects …”

“…, 임동혁 1) , 문선인 1) , 버룰마 1) , 최영숙 2) , 박충희 3) , 김근배 3) , 유승도 3) , 최병선 4) , 박정덕 4) , 김용대 1) , 김헌 1) 충북대학교 의과대학 예방의학교실 1) , 식품의약품안전처 의료기기안전국 허가심사팀 2) 국립환경과학원 환경건강연구부 환경보건연구과 3) , 중앙대학교 의과대학 예방의학교실 4) …”