ABC | Volume 112, Nº4, April 2019

Original Article Effects of Chronic Exposure to Mercury on Angiotensin-Converting Enzyme Activity and Oxidative Stress in Normotensive and Hypertensive Rats Dalton Valentim Vassallo, 1,2 Maylla Ronacher Simões, 1 Karina Giuberti, 1 Bruna Fernandes Azevedo, 1 Rogerio Faustino Ribeiro Junior, 1 Mercedes Salaices, 3,4 Ivanita Stefanon 1 Departamento de Ciências Fisiológicas - Universidade Federal do Espírito Santo, 1 Vitória, ES – Brazil Centro de Ciências da Saúde de Vitória - Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória (EMESCAM), 2 Vitória, ES – Brazil Departamento de Farmacologia - Universidade Autônoma de Madri – Espanha Instituto de Investigación Sanitária Hospital La Paz, 3 Madri – Spain CIBER de Enfermidades Cardiovasculares, 4 Madri – Spain Mailing Address: Maylla Ronacher Simões • Departamento de Ciências Fisiológicas - Universidade Federal do Espírito Santo - Av. Marechal Campos, 1468. Postal Code 29043-900, Maruípe, Vitória, ES – Brazil E-mail: yllars@hotmail.com, mayllaronacher@gmail.com Manuscript received April 27, 2018, revised manuscript July 04, 2018, accepted August 02, 2018 DOI: 10.5935/abc.20180271 Abstract Background: Mercury’s deleterious effects are associated with increased cardiovascular risk. Objective: To determine whether chronic exposure to inorganic mercury increases the activity of angiotensin-converting enzyme and its relationship with oxidative stress in several organs and tissues. Methods: We studied male Wistar and spontaneously hypertensive rats (SHR) (3-month-old) exposed or not to HgCl 2 for 30 days. At the end of treatment, we investigated the following: changes in body weight, hemodynamic parameters, angiotensin‑converting enzyme (ACE) activity and oxidative stress in the heart, aorta, lung, brain and kidney in hypertensive compared to normotensive animals. A value of p < 0.05 was considered significant. Results: Chronic exposure to HgCl 2 did not affect weight gain in either group. Systolic blood pressure, measured weekly, did not increase in Wistar rats but showed a small increase in SHR rats. We also observed increases in left ventricular end-diastolic pressure and ACE activity in the plasma and hearts of normotensive rats. In the SHR+Hg group, ACE activity increased in plasma but decreased in kidney, lung, heart, brain and aorta. Oxidative stress was assessed indirectly by malondialdehyde (MDA) production, which increased in Hg-treated rats in both plasma and heart. In the SHR+Hg group, MDA increased in heart and aorta and decreased in lungs and brain. Conclusion: These results suggest that chronic exposure to inorganic mercury aggravates hypertension and produces more expressive changes in ACE activity and oxidative stress in SHRs. Such exposure affects the cardiovascular system, representing a risk factor for the development of cardiovascular disorders in normotensive rats and worsening of pre-existing risks for hypertension. (Arq Bras Cardiol. 2019; 112(4):374-380) Keywords: Mercury Poisoning; Oxidative Stress/radiation effects; Peptidyl-Dipeptidase A; Hypertension; Rats. Introduction Mercury is a toxic metal that causes harmful effects on the cardiovascular system. Blood concentrations levels of 8 ng/ mL are found in exposed individuals, 1,2 which might have a relationship with hypertension development. 3 Several reports showed that mercury induces oxidative stress and might damage several organs and systems. 4-9 In addition, increased mercury exposure has been associated with cardiovascular diseases, such as hypertension, carotid atherosclerosis, myocardial infarction and coronary heart disease. 10,11 Moreover, oxidative stress is reported to be an efficient mechanism for generation of oxidized low‑density lipoprotein and subsequently atherosclerosis; 12,13 then, generation of advanced glycation end-products and participation of inflammatory cells take place, sustaining vascular injury. 14 One of the main harmful actions of mercury is the generation of oxygen free radicals. NADPH oxidase activation and cyclooxygenase (COX) stimulation induced by mercury may trigger the production of reactive oxygen species (ROS). 11,15,16 Moreover, in animal models chronic mercury exposure for 30 days promoted contractility dysfunction in isolated hearts as a result of decreased Na + -K + -ATPase (NKA) activity, reduction in sodium/calcium exchanger (NCX) and sarco/endoplasmic reticulum calcium ATPase (SERCA) activity and increased phospholamban (PLB) expression. 17 Although no effects on blood pressure, heart rate or left ventricular systolic pressure have been reported, mercury causes a small increase in left ventricular end-diastolic pressure in rats. 17 374