Environmental contamination has exposed humans to various metal agents, including mercury. This exposure is more common than expected, and the health consequences of such exposure remain unclear. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing. Many studies show that high exposure to mercury induces changes in the central nervous system, potentially resulting in irritability, fatigue, behavioral changes, tremors, headaches, hearing and cognitive loss, dysarthria, incoordination, hallucinations, and death. In the cardiovascular system, mercury induces hypertension in humans and animals that has wide-ranging consequences, including alterations in endothelial function. The results described in this paper indicate that mercury exposure, even at low doses, affects endothelial and cardiovascular function. As a result, the reference values defining the limits for the absence of danger should be reduced.

Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg/100g; subsequent doses: 0.125μg/100g, intramuscular, 30days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20μg/dL) were used. Lead blood levels of treated rats attained 21.7±2.38μg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension.

Lead (Pb) induces adverse effects when it chronically accumulates in the body, including effects on the nervous and cardiovascular systems. Wistar rats were exposed to lead acetate for 30 days (first dose 4 µg/100 g followed by 0.05 µg/100 g/day, i.m.) to investigate the cardiovascular system impact on the autonomic control. The femoral artery and vein were catheterised to perform hemodynamic evaluations in awake rats: heart rate variability (HRV), baroreflex sensitivity, cardiopulmonary reflex and hemodynamic responses to vagal and sympathetic pharmacological blockade. Rats exposed to Pb exhibited a higher blood pressure and reduced HRV in the time domain when compared to the saline-injected group. Spectral analysis of the HRV in the frequency-domain showed an augmented low-frequency component of the spectrum. Methylatropine and atenolol administration suggest increased sympathetic tone and reduced vagal tone on the control of heart rate. Chronic Pb exposure decreased the sensitivity of the baroreflex without significantly changing the cardiopulmonary reflex. This study demonstrated for the first time in an animal model of a controlled, low-dose chronic lead exposure that cardiovascular changes, such as arterial hypertension, are accompanied by impaired autonomic control of the cardiovascular system, as characterised by reduced baroreflex sensitivity and a sympathovagal imbalance.

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.

The present studies were conducted to changes arising from mercury poisoning in the central nervous system (CNS), with a focus on determining the receptors and neurotransmitters involved. Currently, little is known regarding the neurological basis of the cardiopulmonary effects of mercury poisoning. We evaluated changes in systolic arterial pressure (SAP), diastolic arterial pressure (DAP), respiratory rate (RR) and heart rate (HR) following a 5 μl intracisternal (i.c) injection of mercuric chloride (HgCl(2)) and the participation of the autonomic nervous system in these responses. 58 animals were utilized and distributed randomly into 10 groups and administered a 5 μL intracisternal injection of 0.68 μg/kg HgCl(2) (n=7), 1.2 μg/kg HgCl(2) (n=7), 2.4 μg/kg HgCl(2) (n=7), 60 μg/kg HgCl(2) (n=7), 120 μg/kg HgCl(2) (n=3), saline (control) (n=7), 60 μg/kg HgCl(2) plus prazosin (n=6), saline plus prazosin (n=6), 60 μg/kg HgCl(2) plus metilatropina (n=4) or saline plus metilatropina (n=4)HgCl(2). Anesthesia was induced with halothane and maintained as needed with urethane (1.2 g/kg) administered intravenously (i.v.) through a cannula placed in the left femoral vein. The left femoral artery was also cannulated to record systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR). A tracheotomy was performed to record respiratory rate. Animals were placed in a stereotaxic frame, and the cisterna magna was exposed. After a stabilization period, solutions (saline or HgCl(2)) were injected i.c., and cardiopulmonary responses were recorded for 50 min. Involvement of the autonomic nervous system was assessed through the i.v. injection of hexamethonium (20 mg/kg), prazosin (1 mg/kg) and methylatropine (1 mg/kg) 10 min before the i.c. injection of HgCl(2) or saline. Treatment with 0.68, 1.2, 2.4 μg/kg HgCl(2) or saline did not modify basal cardiorespiratory parameters, whereas the 120 μg/kg dose induced acute toxicity, provoking respiratory arrest and death. The administration of 60 μg/kg HgCl(2), however, induced significant increases (p<0.05) in SAP at the 30°, 40° and 50° min, timepoints and DAP at the 5°, 10°, 20°, 30°, 40° and 50° timepoints. RR was significantly decreased at the 5°, 10°, 20°, 40° and 50° min timepoints; however, there was no change in HR. Hexamethonium administration, which causes non-specific inhibition of the autonomic nervous system, abolished the observed cardiorespiratory effects. Similarly, prazosin, a α(1)-adrenoceptor blocker that specifically inhibits sympathetic nervous system function, abolished HgCl(2) induced increases in SAP and DAP without affecting HR and RR. Methylatropine (1 mg/Kg), a parasympathetic nervous system inhibitor, exacerbated the effects of HgCl(2) and caused slow-onset respiratory depression, culminating in respiratory arrest and death. Our results demonstrate that increases in SAP and DAP induced by the i.c. injection of mercuric chloride are mediated by activation of the sympathetic nervous system.