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Xanthine Oxidase Activation Modulates the Endothelial (Vascular) Dysfunction Related to HgCl2 Exposure Plus Myocardial Infarction in Rats

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Abstract

Heavy metal exposure is associated with cardiovascular diseases such as myocardial infarction (MI). Vascular dysfunction is related to both the causes and the consequences of MI. We investigated whether chronic exposure to low doses of mercury chloride (HgCl2) worsens MI-induced endothelial dysfunction 7 days after MI. Male Wistar rats were divided into four groups: Control (vehicle), HgCl2 (4 weeks of exposure), surgically induced MI and combined HgCl2-MI. Morphological and hemodynamic measurements were used to characterize the MI model 7 days after the insult. Vascular reactivity was evaluated in aortic rings. Chronic HgCl2 exposure did not cause more heart injury than MI alone in terms of the morphological or hemodynamic parameters. Vascular reactivity increased in all groups, but the combination of HgCl2-MI increased the vasorelaxation induced by ACh compared with the HgCl2 and MI groups. Results showed reduced endothelial nitric oxide synthase (eNOS) protein expression in the MI group; increased iNOS activity in the HgCl2-MI group, although without enough magnitude to reverse the reduction in NO bioavailability; and increased phenylephrine response in the HgCl2-MI group due to an increase in ROS production, notably via xanthine oxidase (XO). Results suggest that the combination of 1 month pre-exposure of HgCl2 before MI changed the endothelial generation of oxidative stress induced by mercury exposure from NADPH oxidase pathway to XO (xanthine oxidase)-dependent ROS production.

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Acknowledgements

This study was supported by Grants from No 54685435/2011-FAPES (Fundação de Amparo à Pesquisa do Espírito Santo), No 48511935/2009 PRONEX—FAPES/CNPq (FAPES/Conselho Nacional de Desenvolvimento Cientifico e Tecnológico) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior).

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Authors and Affiliations

  1. Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES, 29040-091, Brazil

    Thaís de O. Faria, Maylla Ronacher Simões, Dalton Valentim Vassallo, Ludimila Forechi, Camila Cruz Pereira Almenara, Bruna Antoniassi Marchezini, Ivanita Stefanon & Paula Frizera Vassallo

  2. Health Science Center of Vitória-EMESCAM, Vitória, ES, 29045-402, Brazil

    Dalton Valentim Vassallo

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  1. Thaís de O. Faria
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  2. Maylla Ronacher Simões
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  3. Dalton Valentim Vassallo
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  5. Camila Cruz Pereira Almenara
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  8. Paula Frizera Vassallo
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Correspondence to Maylla Ronacher Simões.

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Faria, T.d., Simões, M.R., Vassallo, D.V. et al. Xanthine Oxidase Activation Modulates the Endothelial (Vascular) Dysfunction Related to HgCl2 Exposure Plus Myocardial Infarction in Rats. Cardiovasc Toxicol 18, 161–174 (2018). https://doi.org/10.1007/s12012-017-9427-x

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