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Long-term Mercury Exposure Accelerates the Development of Hypertension in Prehypertensive Spontaneously Hypertensive Rats Inducing Endothelial Dysfunction: the Role of Oxidative Stress and Cyclooxygenase-2

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Abstract

Mercury is a metal widely dispersed in nature that when in contact with human organism, it damages the cardiovascular system. Long-term mercury exposure for 30 days induces endothelial dysfunction without blood pressure changes in normotensive adult rats. However, it is not known whether exposure to mercury can exacerbate endothelial dysfunction and hypertension development in predisposed animals. Thus, we aimed to investigate the effects of long-term mercury exposure on the blood pressure (BP) and in the isolated aortas of young normotensive and prehypertensive spontaneously hypertensive rats (SHRs). Four-week-old male Wistar rats and SHRs were treated daily with mercury chloride (HgCl2) (1st dose, 4.6 μg/kg; subsequent dose, 0.07 μg/kg/day, im, 30 days) or vehicle. BP was assessed weekly and the vascular reactivity to phenylephrine was evaluated in isolated aorta from rats exposed or not to mercury. Mercury exposure did not affect BP in young Wistar rats but accelerated the development of hypertension in young SHRs. Vascular reactivity to phenylephrine increased only in the aorta from mercury-exposed SHRs. While HgCl2 exposure in SHRs did not alter nitric oxide production, we observed increased superoxide anion production and decreased superoxide dismutase-1 protein expression, and enhanced cyclooxygenase-2 (COX-2) participation with increased prostaglandin (PGE2) production and decreased prostacyclin. In the Wistar group, mercury exposure did not alter superoxide anion production or the COX-2 pathway. Mercury exposure accelerated the natural course of hypertension in young SHRs and increased oxidative stress associated with reduced participation of antioxidant enzymes, an activated COX-2 pathway, thereby producing endothelial dysfunction, which is a risk factor in prehypertensive individuals.

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Funding

This work was supported by grants from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES—Finance code 001); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Espírito Santo (FAPES—Grant 80600115, 73370215, 80598773). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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  1. Department of Physiological Sciences, Federal University of Espirito Santo, Av. Marechal Campos, 1468, Vitória, ES, 29040-091, Brazil

    Rakel Passos Simões, Paloma Batista Almeida Fardin, Maylla Ronacher Simões, Dalton Valentim Vassallo & Alessandra Simão Padilha

  2. School of Sciences of Santa Casa de Misericórdia de Vitoria- EMESCAM, Vitória, ES, Brazil

    Dalton Valentim Vassallo

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  1. Rakel Passos Simões
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Correspondence to Alessandra Simão Padilha.

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Simões, R.P., Fardin, P.B.A., Simões, M.R. et al. Long-term Mercury Exposure Accelerates the Development of Hypertension in Prehypertensive Spontaneously Hypertensive Rats Inducing Endothelial Dysfunction: the Role of Oxidative Stress and Cyclooxygenase-2. Biol Trace Elem Res 196, 565–578 (2020). https://doi.org/10.1007/s12011-019-01952-8

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