title: Cadmium exposure induces vascular injury due to endothelial oxidative stress: the role of local angiotensin II and COX-2.
abstract: Cadmium is an environmental pollutant that is closely linked with cardiovascular diseases, such as atherosclerosis and hypertension. Moreover, cadmium can induce an increase in oxidative stress. One of the main sites affected by oxidative stress is the aorta, which consequently develops atherosclerosis. However, there are few reports demonstrating aortic effects induced by small concentrations of cadmium that are similar to those found in the blood resulting from occupational exposure. Furthermore, several studies have reported on chronic cadmium exposure, and the results of these studies may have been influenced by the secondary effects induced by this metal, such as hypertension. Therefore, we investigated the effects of acute cadmium exposure on the vascular reactivity to phenylephrine of aortic rings isolated from male Wistar rats. Cadmium increased phenylephrine reactivity without changing the vasorelaxation induced by acetylcholine and sodium nitroprusside. Endothelial damage or incubation with L-NAME shifted the phenylephrine concentration-response curves leftward in arteries incubated with or without cadmium, but the curves were shifted to a lesser degree after cadmium incubation. Enalapril, losartan, the nonselective COX inhibitor indomethacin, the TXA(2) synthase inhibitor furegrelate, the selective COX-2 inhibitor NS 398, the TP receptor antagonist SQ 29.548, the EP1 receptor antagonist SC 19.220, superoxide dismutase, and the NADPH oxidase inhibitor apocynin partially reverted the cadmium-induced effects on the reactivity to phenylephrine. Cadmium exposure increased vasoconstrictor activity by reducing NO bioavailability owing to the increased production of ROS by NADPH oxidase. The results of the tested cadmium concentration, which is below the reference values, suggest that acute cadmium exposure may induce vascular injury through endothelial oxidative stress. These data contribute to the evidence indicating that cadmium is a high risk to public health.
authors: Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, 29040-091 Vitória, ES, Brazil. Electronic address: jhulikeliangeli@gmail.com.
authors: Jhuli Keli
authors: JK
authors: Angeli
authors: Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, 29040-091 Vitória, ES, Brazil.
authors: Camila Almenara
authors: CA
authors: Cruz Pereira
authors: Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, 29040-091 Vitória, ES, Brazil.
authors: Thaís
authors: T
authors: de Oliveira Faria
authors: Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, 29040-091 Vitória, ES, Brazil.
authors: Ivanita
authors: I
authors: Stefanon
authors: Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, 29040-091 Vitória, ES, Brazil.
authors: Alessandra Simão
authors: AS
authors: Padilha
authors: Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, 29040-091 Vitória, ES, Brazil; Escola de Ensino Superior da Santa Casa de Misericórdia de Vitória, EMESCAM, Vitória, ES, Brazil.
authors: Dalton Valentim
authors: DV
authors: Vassallo
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002104:Cadmium / Q000633:toxicity*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress; D010656:Phenylephrine / Q000494:pharmacology; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation
chemical_list: D004785:Environmental Pollutants; D014662:Vasoconstrictor Agents; D002104:Cadmium; D000804:Angiotensin II; D010656:Phenylephrine; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat
keywords: Aorta; COX-2; Free radicals; Local renin–angiotensin system; ROS