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 2 – Values of systolic blood pressure (SBP in mmHg) measured by tail plethysmography in Wistar rats and spontaneously hypertensive rats (SHRs) before and after treatment for 30 days with HgCl 2 . Wistar CT n = 5 Wistar Hg n = 5 SHR CT n = 5 SHR Hg n = 5 SBP – Day 0 (mmHg) 123 ± 13 131 ± 15 205 ± 15 198 ± 22 SBP – Day 7 (mmHg) 119 ± 4 132 ± 9 221 ± 18 197 ± 18 SBP – Day 14 (mmHg) 115 ± 10 135 ± 9 219 ± 9 199 ± 29 SBP – Day 21 (mmHg) 132 ± 17 142 ± 14 200 ± 13 199 ± 9 SBP – Day 30 (mmHg) 117 ± 6 143 ± 11 220 ± 21 232 ± 19 # Results represent the mean ± SD; n: number of animals used. One-way ANOVA, post hoc Tukey’s for all groups. # p < 0.05 vs. SHR treated with mercury at day 0 Table 3 – Hemodynamic parameters from untreated and mercury (HgCl 2 )-treated Wistar rats and spontaneously hypertensive rats (SHRs) Wistar Control n = 6 Wistar HgCl 2 -treated n = 7 SHR Control n = 6 SHR HgCl 2 -treated n = 7 SBP (mmHg) 105 ± 10 97 ± 11 105 ± 7 113 ± 8 DBP (mmHg) 71 ± 10 67 ± 11 58 ± 5 68 ± 11 HR (bpm) 324 ± 88 325 ± 58 343 ± 32 341 ± 34 LVSP (mmHg) 114 ± 20 107 ± 16 117 ± 22 112 ± 8 LVEDP (mmHg) 0.256 ± 1 3.31 ± 1* 1.11 ± 0.2 0.493 ± 0.5 +dP/dt LV (mmHg/s) 8627 ± 3378 8500 ± 2419 7360 ± 1854 7001 ± 1921 -dP/dt LV -6270 ± 1232 -6249 ± 1234 -7169 ± 1173 -6524 ± 1131 RVSP (mmHg) 32 ± 10 29 ± 5 29 ± 5 33 ± 5 RVEDP (mmHg) -1.080 ± 1 1.10 ± 2 -0.472 ± 1 0.459 ± 0.3 +dP/dt RV (mmHg/s) 3339 ± 2202 1758 ± 435 2776 ± 1056 2171 ± 405 – dP/dt RV (mmHg/s) -2560 ± 1553 -1387 ± 469 -1833 ± 478 -1695 ± 368 Changes in systolic (SBP) and diastolic (DBP) pressure, heart rate (HR), left and right ventricle systolic pressure (LVSP, RVSP), left and right ventricle end diastolic pressure (LVEDP, RVEDP) and positive (+dP/dt) and negative first-time derivatives (-dP/dt) from the left and right ventricles of Control and HgCl 2 -treated rats. The results represent the mean ± SD. n-Number of animals used. One-way ANOVA, post hoc Tukey’s. *p < 0.05 vs Wistar Control. The reduction of NO bioavailability is a hallmark resulting from the increase in ROS generation contributing to the development of cardiovascular diseases such as atherosclerosis and hypertension. 10,11,34 The interaction of superoxide anionwith NO generates peroxynitrite that decreases NO bioavailability increasing vascular reactivity. 20-22 In fact, our previous studies have associated mercury exposure with increased oxidative stress and the reduction of NO bioavailability. 15,19 In addition, it has been shown that an increase of the local ACE activity could increase NADPH oxidase activity 16 40 and ROS in the aortas of normotensive and SHRs. Therefore, we investigated whether mercury effects alter the renin-angiotensin system and oxidative stress in the organs and tissues of hypertensive and normotensive rats. The increase in ACE activity induced by mercury could lead to increased activity of NADPH oxidase, which could, in turn, increase the release of ROS, generating an oxidative stress, as observed in this study. Considering that both Hg and increased ACE activity can induce oxidative stress, we should observe a correlation between the amount of oxidative stress and ACE activity measured by MDA. An interesting aspect is that ACE activity levels and MDA concentrations showed similar behavior in plasma and organs investigated. Also, it is of note that both ACE activity and MDA concentrations showed more expressive changes in HgCl 2 - treated SHRs. Similarly, inorganic mercury treatment aggravated hypertension in SHRs, suggesting that a pre-existing hypertensive condition enhances inorganic mercury action. ROS are damped in the plasma of all locations where they are produced, and consequently, it is expected an increase in MDA. We have shown that plasma ACE activity increases after acute exposure to low mercury concentrations and reduces after exposure to high concentrations. 18,39 However, we might speculate that in the SHR group, when exposed to mercury, tissues that produce more ROS, such as the aorta, lung and kidney, ACE activity is reduced. Similarly, in the brain tissue, which concentrates mercury, ACE activity also decreased. LVEDP increments in Wistar rats could be explained by the local increase in ACE activity and oxidative stress in the heart. These two factors might explain the small, but significant increase in LVEDP, probably induced by a calcium overload. Althoughwe cannot give aproper explanation for all the events, it can be suggested that mercury, even at concentrations that do not affect arterial pressure and weight gain in normotensive rats, affects ACE activity and oxidative stress. However, in hypertensive animals, inorganic mercury actions were more expressive. These findings give rise to questions that are not addressed by our results: can exposure tomercury inhibit ACE activity in situations where it is already increased? Does ACE activity in different organs 377