ABC | Volume 112, Nº4, April 2019

Original Article Vassallo et al Mercury increases ACE activity and oxidative stress Arq Bras Cardiol. 2019; 112(4):374-380 Table 1 – Body Weight (BW), Brain/BW, Heart/BW, Kidney/BW, Lung/BW, Adrenals/BW, Spleen/PC and Liver/PC from HgCl 2 -treated and non‑treated Wistar rats and spontaneously hypertensive rats (SHRs) Wistar Control n = 6 Wistar HgCl 2 -treated n = 8 SHR Control n = 9 SHR HgCl 2 -treated n = 9 Body weight (BW) (g) 399 ± 58.3 384 ± 18.1 216 ± 20.1* † 222 ± 14.4* † Brain/BW (mg/g) 4.58 ± 0.7 4.69 ± 0.5 7.48 ± 0.7* † 7.41 ± 0.5* † Heart/BW (mg/g) 3.06 ± 0.6 3.43 ± 0.2 3.77 ± 0.2 3.81± 0.2 Kidney/BW (mg/g) 6.44 ± 1.7 6.53 ± 0.5 6.78 ± 0.3 6.80 ± 0.6 Lung/BW (mg/g) 3.97 ± 1.5 4.53 ± 0.6 6.48 ± 1.2* † 7.91 ± 1.2* † Results represent mean ± SD; n: number of animals used. One-way ANOVA, post hoc Tukey’s. *p < 0.05 compared with the Wistar control and † p < 0.05 compared with HgCl 2 : treated Wistar rats. Smirnov test. Differences were analysed using one-way ANOVA, followed by a post hoc Tukey test (GraphPad Prism Software, San Diego, CA). A p value < 0.05 was considered significant. Results At 30 days of mercury treatment, Wistar controls, Wistar treated rats, and treated and untreated SHRs had similar body weights, although the SHRs had lower body weights when compared with Wistar rats (Table 1). Table 1 also shows that several organs, including the brain, heart, kidney and lungs, presented similar weights, normalized by body weight, which did not change after mercury treatment. Indirect SBP measured at day zero in awake rats showed that SHRs had a higher mean arterial pressure compared with Wistar rats (Table 2). However, at the end of the treatment, mercury produced a significant increment of blood pressure only in HgCl 2 -treated SHR rats (Table 2). Arterial blood pressures, ventricular pressures and their respective derivatives, and HR measurements in anaesthetized rats were not different between groups (Table 3), but the LVEDP increased after Hg treatment in the Wistar group, as previously reported. 17 It has been reported in animal and human studies that mercury increases free radical production leading to an oxidative stress. 4,24,30,31 We then evaluated the oxidant state in the blood and in several other tissues by measuring MDA levels (Table 4). MDA plasma levels were greater in mercury-treated than in untreated Wistar rats but did not change in SHRs. Mercury treatment increased MDA levels in the heart in both Wistar and SHRs. In the aorta, different from plasma, MDA levels were increased in mercury-treated SHRs but not inWistar rats. For brain and lungs, no changes were observed for MDA levels in mercury-treated Wistar rats, but a reduction occurred in SHRs. For kidneys, mercury treatment reduced MDA levels in both Wistar and SHR mercury-treated groups. Since angiotensin II is reported to increase ROS and mercury increases ACE, 32,33 we investigated whether ACE activity was altered after 30 days of mercury treatment in Wistar and SHR groups. Table 5 shows that plasma ACE levels increased in both groups after mercury treatment. In the hearts of Wistar rats, mercury induced a slight ACE activity increment, but no changes were observed in the aorta, lungs, brain or kidneys. However, in mercury-treated SHRs, ACE activity was reduced in the heart, aorta, lungs, brain and kidneys. Interestingly, ACE activity was higher in the heart, aorta and kidneys and lower in plasma of SHR controls compared with Wistar controls. Discussion The results presented here suggest that Wistar rats and SHRs, submitted to chronic exposure to inorganic mercury for 30 days, have blood concentrations similar to exposed individuals. 1,2 In addition, HgCl 2 -treated SHR, but notWistar rats have increased blood pressure at the end of treatment. The intervention also influenced ACE activity and oxidative stress, by increasing or decreasing them, mainly in SHRs. Previous reports showed that changes resulting from chronic exposure to mercury have been focused on its toxic effects on the cardiovascular system and the associations with hypertension, carotid atherosclerosis, myocardial infarction and coronary heart disease. 9,10,34 Mercury exposure, both acute and chronic, affects the heart and endothelial function, reducing NO bioavailability and increasing ACE and NADPH activities. 15,18,19 Moreover, studies in rats showed that body weight gain and arterial pressure were not affected when chronic exposure was performed, 4,17 suggesting that this treatment was not sufficient, in either amount or time, to produce changes. Our results reproduced those findings, showing no changes in body weight gain; additionally, similar behaviour was observed for the heart, brain, kidneys and lung, reinforcing the suggestion that this treatment is not sufficient to produce these changes, although cardiovascular function began to be affected. Regarding the hemodynamic evaluation, no changes were observed in the left or right ventricle in Wistar rats or SHRs. Only an increment of LVEDP was observed in normotensive rats treated with mercury, indicating some deleterious effects of mercury on ventricular function. 35 Right ventricular pressures were investigated because of our previous report showing that under acute mercury exposure (0.5 mg/kg), there was an increase in right ventricular systolic pressure because of pulmonary hypertension, 3,36-39 which was not observed with chronic treatment in the present study. The fact that lung ACE activity was unaffected in both Wistar groups, although slightly reduced in HgCl 2 -treated SHRs might explain why the right ventricular pressures remained unchanged. 376