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Mercury Poisoning Presenting With Hypertension: Report of 2 Cases
BRIEF OBSERVATION
ARTICLE IN PRESS
Mercury Poisoning Presenting With Hypertension: Report of 2 Cases Jin Yan, MD a, Yujie Pan a, Ziren Tang b, Yuguo Song a a b
Department of Occupational Medicine and Clinical Toxicology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China; Department of Emergency, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
ABSTRACT BACKGROUND: Mercury poisoning can cause damage to multiple organs. Secondary hypertension, which is usually misdiagnosed and mistreated, has been rarely reported in cases of mercury poisoning. METHODS: We herein present 2 cases of hypertension as the main manifestation of mercury poisoning. RESULTS: Case 1 involved a 42-year-old man with blood pressure of 230/190 mm Hg and urinary mercury level of 131.54 μmol/molCr. The patient had been repeatedly exposed to mercury at his workplace and had been admitted to our department many times. His hypertension quickly normalized after every chelation treatment. Case 2 involved a 10-year-old girl with hypertension (150/110 mm Hg), rash, and convulsions. She was found to have elevated blood levels of renin, angiotensin II, and aldosterone as well as an elevated urinary mercury level. Her hypertension recovered soon after chelation treatment. CONCLUSIONS: Mercury poisoning can cause secondary hypertension as the main clinical manifestation or together with multiorgan damage. Renin-angiotensin system activation may be involved in the occurrence and development of hypertension. © 2019 Elsevier Inc. All rights reserved. All rights reserved. • The American Journal of Medicine (2019) xxx:xxx-xxx KEYWORDS: Hypertension; Mercury poisoning; Misdiagnosis
INTRODUCTION Mercury is a heavy metal found naturally in the environment. It exists in three forms: elemental mercury, inorganic mercury compounds, and organic mercury.1 Mercury poisoning is still a common disease in China. Most cases of mercury poisoning are caused by occupational exposure, accidental ingestion of mercury-containing drugs (some Chinese traditional medicines), or the use of facial cosmetics containing mercury.2
Funding: This work was funded by the National Natural Science Foundation of China (Grant 81773373, 81172614 and Grant 81441089). Conflicts of Interest: None. All authors had access to the data and a role in writing this manuscript. Requests for reprints should be addressed to: Yuguo Song, MD, PhD., Department of Occupational Medicine and Clinical Toxicology, Beijing Chaoyang Hospital, Capital Medical University, NO. 8, Gongtinan Road, Chaoyang District, Beijing 100020, China or to: Ziren Tang, MD, PhD, Department of Emergency, Beijing Chaoyang Hospital, Capital Medical University, NO. 8, Gongtinan Road, Chaoyang District, Beijing 100020, China. E-mail addresses: [email protected], [email protected] 0002-9343/© 2019 Elsevier Inc. All rights reserved. All rights reserved. https://doi.org/10.1016/j.amjmed.2019.03.050
Mercury poisoning induces damage to multiple systems such as the skin, muscular and nervous systems, kidneys, and cardiovascular system. Its clinical manifestations include irritability, fatigue, dizziness, headache, tremor, gingivitis, proteinuria, and toxic encephalopathy.2 Cardiovascular toxicity may present as tachycardia or hypertension. However, hypertension secondary to mercury poisoning has been rarely reported and is usually misdiagnosed and mistreated. We herein report 2 cases of hypertension that resulted from mercury poisoning. The clinical characteristics, clinical treatment, and prognosis are summarized in each case. Unusual presentations such as these may advance our understanding of mercury toxicity as well as the mechanism and treatment of hypertension secondary to mercury poisoning.
CASE 1 A 42-year-old man was admitted to our department with a 16-year history of intermittent dizziness that had become aggravated during the past month. Twenty years before
ARTICLE IN PRESS
The American Journal of Medicine, Vol xxx, No xxx, ▪▪ 2019
2
treatment, the patient’s blood pressure had normalized at presentation, the patient had become engaged in individual 120–130/60–80 mm Hg (Figure 1), and his symptoms of dizalchemy in a personal factory (300–500 m2), where he extracted ziness and headache had improved. As shown in Figure 1, gold from mineral powder with mercury (10 kg of mercury with the decrease of urinary mercury concentration, the used for each alchemic extraction). Gold amalgam solution patient’s blood pressure quickly normalized as his urinary was obtained by elutriation, and mercury was extruded for mercury concentration decreased. He was instructed to recycling. He worked 2 weeks every month for 7 to 8 hours avoid additional exposure to per day. He occasionally wore a mercury. cotton mask but used no other CLINICAL SIGNIFICANCE personal protective equipment in the workplace. Sixteen years The possibility of mercury poisoning should CASE 2 before admission (4 years after be excluded in the diagnosis and treatment beginning his alchemic work), A 10-year-old girl was hospiof unknown hypertension with a history of the patient developed dizziness talized in our department betoxic exposure. and occasional epistaxis. He excause of a 3-month history of After chelation treatment, the hypertension perienced no fever, cough, nauhypertension, skin rash, and secondary to mercury poisoning rapidly recovers. sea, insomnia, or hand convulsions. Three months prefibrillation. His blood pressure viously, the patient had presented was 230/190 mm Hg and was diwith erythematous papules and agnosed with primary hypertension. He began taking oral pruritus mainly on her trunk and extremities. Her hands exhibnimodipine but not regularly. His blood pressure was not ited glove-like peeling with burning pain. Her blood pressure well controlled, and his dizziness and headache remained. was measured at 150/110 mm Hg. She had also developed Six years before the current presentation, the patient paroxysmal convulsions; when her eyes turned upward, her visited our department because his workmates had developed limbs twitched and consciousness was lost. These symptoms similar symptoms of dizziness and headache and were were relieved several minutes after onset and occurred rediagnosed with mercury poisoning. The patient’s blood peatedly more than 10 times every day. The patient also had pressure was 230/180 mm Hg, and his urinary mercury blurred vision and progressive exacerbation of visual opacity. level was 131.54 μmol/molCr (reference range, 0.00– She was admitted to several hospitals for treatment, but none 2.25 μmol/molCr). He began regular treatment with intrawere successful. The results of a computed tomography (CT) muscular dimercaptopropane sulfonate (DMPS) at 0.25 g and magnetic resonance imaging (MRI) of the head, performed daily for 3 days. After 2 courses of this mercury removal outside our hospital, were normal. A skin biopsy showed that treatment, his blood pressure substantially decreased, flucthe muscle fibers had lost their angular appearance and that tuating within the range of 100/90 to 140/90 mm Hg; his inflammatory cells were scattered throughout the interstitium. 24-hour urinary mercury excretion decreased from 5503.4 to Her blood potassium level was 2.83 to 3.25 mmol/L (reference 2197.1 μg/d; and his dizziness and headache improved. After range, 3.5–5.5 mmol/L). Her plasma renin activity in the 5 courses of DMPS treatment, he had clinically recovered horizontal and vertical positions was N 12 μg/L.h (reference and had a normal urinary mercury level. range, 0.05–0.79 μg/L.h) and N 12 μg/L.h (reference range, The patient resumed working in the described smelting 0.93–6.56 μg/L.h), respectively. Her blood level of angiotensin workshop after discharge. He was repeatedly admitted to II in the horizontal and vertical positions was 70.9 ng/L our department 3 times within 5 years for mercury poisoning (reference range, 28.2–52.2 ng/L) and 481.0 ng/L (reference characterized by hypertension and an elevated urinary mercury range, 55.3–115.3 ng/L), respectively. Her blood aldosterone level. His hypertension quickly normalized after each chelalevel in the horizontal and vertical positions was 232.1 ng/L tion treatment. One month before admission, the patient (reference range, 48.5–123.5 ng/L) and 285.2 ng/L (reference presented with recurrence of dizziness but no other abnormalities such as insomnia, hand fibrillation, or oral ulceration. His blood pressure was 150/90 mm Hg and his urinary mercury level was elevated at 12.676 μmol/molCr. Physical examination revealed no other abnormalities and normal vital signs. He had clear consciousness and was in good spirits without scleral yellowing or skin rash. Routine laboratory tests showed normal blood and urine parameters. His 24hour urinary mercury excretion was 208.2 μg/d (reference Figure 1 Changes in urinary mercury level and blood pressure range, 0.0–45.0 μg/d), and his blood mercury level was in Case 1. With the decrease of urinary mercury concentration, 0.002 mg/L (reference range, 0.000–0.015 mg/L). the patient’s blood pressure quickly normalized. C= course of The patient was treated with intramuscular DMPS at 0.25 g chelation treatment; DBP= diastolic blood pressure; SBP= daily for 3 days. His urinary mercury excretions on the first systolic blood pressure; UMC= urinary mercury 3 days after one course of chelation treatment were 502.4, concentration. 208.2, and 102.5 μg/d, respectively. After 2 courses of
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ARTICLE IN PRESS Yan et al
Mercury Poisoning With Hypertension
range, 63.0–239.6 ng/L), respectively. Her levels of β2microglobulin in urine and blood were 495.7 mg/L and 1557.5 ng/ml, respectively. Upon admission to our department, the patient’s blood pressure was 150/90 mm Hg and her heart rate was 118 beats/min. The skin on her hands, wrists, legs, and feet was red, hot, and rough with signs of scratching. Neurological examination showed no abnormalities. Toxicologic analysis revealed that her urinary mercury level was 0.171 mg/L (reference range, 0.000–0.010 mg/L) before chelation treatment and 1.408 mg/L after chelation treatment. She had normal urinary lead and arsenic levels. On further inquiry regarding her medical history, we found that the patient and her classmates had long played with mercury pearls on their palms in their classroom. Additional investigation revealed mercury poisoning in dozens of her classmates and teachers. The patient was treated with 5 courses of intramuscular DMPS (0.125 g daily for 3 days) as well as symptomatic treatment until her urinary mercury level was normal. After 2 courses of chelation treatment, her blood pressure quickly dropped to normal without the use of antihypertensive drugs, her convulsions disappeared, and her skin rash improved.
3 enzyme activity and increased RAS activation.4 In Case 2, we also found increased blood levels of renin, angiotensin, and aldosterone, suggesting that activation of the RAS is one mechanism of the occurrence and development of hypertension. In addition, some studies have suggested that the potential mechanisms of mercury-related hypertension are increased oxidative stress,1 promotion of free radical stress and lipid peroxidation,5,6 inactivation of paraoxonase,6 endothelial dysfunction,6 and inhibited activation of nuclear factor-κB.1 Hypertension secondary to mercury poisoning often leads to misdiagnosis and delay of appropriate treatment.7 We suggest that the possibility of mercury poisoning should be excluded in the diagnosis and treatment of unknown hypertension with a history of toxic exposure.
CONCLUSIONS Mercury poisoning can present either with hypertension as the main sign or together with multiorgan damage. RAS activation may be involved in the occurrence and development of hypertension. After chelation treatment, the hypertension secondary to mercury poisoning rapidly resolves.
DISCUSSION Rare reports have described mercury poisoning that clinically manifested as hypertension. Our report shows that mercury poisoning can present mainly as hypertension as seen in Case 1 or as hypertension accompanied by serious symptoms as seen in Case 2. The characteristics of hypertension secondary to mercury poisoning as seen in our patients can be summarized as follows: 1) the hypertension can rapidly normalize after mercury removal treatment and recur after reexposure to mercury; 2) the elevated blood levels of renin, angiotensin, and aldosterone in Case 2 indicate that the renin-angiotensin system (RAS) may be involved in the occurrence and development of hypertension; and 3) the prognosis of hypertension secondary to mercury poisoning is good. The mechanisms of mercury toxicity involving the cardiovascular system have not been fully elucidated.3 Mercury exposure reportedly leads to increased angiotensin-converting
References 1. Virtanen JK, Rissanen TH, Voutilainen S, et al. Mercury as a risk factor for cardiovascular diseases. J Nutr Biochem 2007;18(2):75-85. 2. Wang HB, Niu WK. Diagnosis and treatment of mercury poisoning. Chinese J Ind Med 2009;18(3):238-41. 3. Wildemann TM, Siciliano SD, Weber LP. The mechanisms associated with the development of hypertension after exposure to lead, mercury species or their mixtures differs with the metal and the mixture ratio. Toxicology 2016;339:1-8. 4. Rizzetti DA, Da ST, Escobar AG, et al. Mercury-induced vascular dysfunction is mediated by angiotensin II AT-1 receptor upregulation. Environ Res 2018;162:287-96. 5. Zalups RK. Molecular interactions with mercury in the kidney. Pharmacol Rev 2000;52(1):113-43. 6. Fernandes AB, Barros FL, Pecanha FM, et al. Toxic effects of mercury on the cardiovascular and central nervous systems. J Biomed Biotechnol 2012;2012, 949048. 7. Gao Z, Ying X, Yan J, et al. Acute mercury vapor poisoning in a 3-monthold infant: A case report. Clin Chim Acta 2017;465:119-112.
ARTICLE IN PRESS
Mercury Poisoning Presenting With Hypertension: Report of 2 Cases Jin Yan, MD a, Yujie Pan a, Ziren Tang b, Yuguo Song a a b
Department of Occupational Medicine and Clinical Toxicology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China; Department of Emergency, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
ABSTRACT BACKGROUND: Mercury poisoning can cause damage to multiple organs. Secondary hypertension, which is usually misdiagnosed and mistreated, has been rarely reported in cases of mercury poisoning. METHODS: We herein present 2 cases of hypertension as the main manifestation of mercury poisoning. RESULTS: Case 1 involved a 42-year-old man with blood pressure of 230/190 mm Hg and urinary mercury level of 131.54 μmol/molCr. The patient had been repeatedly exposed to mercury at his workplace and had been admitted to our department many times. His hypertension quickly normalized after every chelation treatment. Case 2 involved a 10-year-old girl with hypertension (150/110 mm Hg), rash, and convulsions. She was found to have elevated blood levels of renin, angiotensin II, and aldosterone as well as an elevated urinary mercury level. Her hypertension recovered soon after chelation treatment. CONCLUSIONS: Mercury poisoning can cause secondary hypertension as the main clinical manifestation or together with multiorgan damage. Renin-angiotensin system activation may be involved in the occurrence and development of hypertension. © 2019 Elsevier Inc. All rights reserved. All rights reserved. • The American Journal of Medicine (2019) xxx:xxx-xxx KEYWORDS: Hypertension; Mercury poisoning; Misdiagnosis
INTRODUCTION Mercury is a heavy metal found naturally in the environment. It exists in three forms: elemental mercury, inorganic mercury compounds, and organic mercury.1 Mercury poisoning is still a common disease in China. Most cases of mercury poisoning are caused by occupational exposure, accidental ingestion of mercury-containing drugs (some Chinese traditional medicines), or the use of facial cosmetics containing mercury.2
Funding: This work was funded by the National Natural Science Foundation of China (Grant 81773373, 81172614 and Grant 81441089). Conflicts of Interest: None. All authors had access to the data and a role in writing this manuscript. Requests for reprints should be addressed to: Yuguo Song, MD, PhD., Department of Occupational Medicine and Clinical Toxicology, Beijing Chaoyang Hospital, Capital Medical University, NO. 8, Gongtinan Road, Chaoyang District, Beijing 100020, China or to: Ziren Tang, MD, PhD, Department of Emergency, Beijing Chaoyang Hospital, Capital Medical University, NO. 8, Gongtinan Road, Chaoyang District, Beijing 100020, China. E-mail addresses: [email protected], [email protected] 0002-9343/© 2019 Elsevier Inc. All rights reserved. All rights reserved. https://doi.org/10.1016/j.amjmed.2019.03.050
Mercury poisoning induces damage to multiple systems such as the skin, muscular and nervous systems, kidneys, and cardiovascular system. Its clinical manifestations include irritability, fatigue, dizziness, headache, tremor, gingivitis, proteinuria, and toxic encephalopathy.2 Cardiovascular toxicity may present as tachycardia or hypertension. However, hypertension secondary to mercury poisoning has been rarely reported and is usually misdiagnosed and mistreated. We herein report 2 cases of hypertension that resulted from mercury poisoning. The clinical characteristics, clinical treatment, and prognosis are summarized in each case. Unusual presentations such as these may advance our understanding of mercury toxicity as well as the mechanism and treatment of hypertension secondary to mercury poisoning.
CASE 1 A 42-year-old man was admitted to our department with a 16-year history of intermittent dizziness that had become aggravated during the past month. Twenty years before
ARTICLE IN PRESS
The American Journal of Medicine, Vol xxx, No xxx, ▪▪ 2019
2
treatment, the patient’s blood pressure had normalized at presentation, the patient had become engaged in individual 120–130/60–80 mm Hg (Figure 1), and his symptoms of dizalchemy in a personal factory (300–500 m2), where he extracted ziness and headache had improved. As shown in Figure 1, gold from mineral powder with mercury (10 kg of mercury with the decrease of urinary mercury concentration, the used for each alchemic extraction). Gold amalgam solution patient’s blood pressure quickly normalized as his urinary was obtained by elutriation, and mercury was extruded for mercury concentration decreased. He was instructed to recycling. He worked 2 weeks every month for 7 to 8 hours avoid additional exposure to per day. He occasionally wore a mercury. cotton mask but used no other CLINICAL SIGNIFICANCE personal protective equipment in the workplace. Sixteen years The possibility of mercury poisoning should CASE 2 before admission (4 years after be excluded in the diagnosis and treatment beginning his alchemic work), A 10-year-old girl was hospiof unknown hypertension with a history of the patient developed dizziness talized in our department betoxic exposure. and occasional epistaxis. He excause of a 3-month history of After chelation treatment, the hypertension perienced no fever, cough, nauhypertension, skin rash, and secondary to mercury poisoning rapidly recovers. sea, insomnia, or hand convulsions. Three months prefibrillation. His blood pressure viously, the patient had presented was 230/190 mm Hg and was diwith erythematous papules and agnosed with primary hypertension. He began taking oral pruritus mainly on her trunk and extremities. Her hands exhibnimodipine but not regularly. His blood pressure was not ited glove-like peeling with burning pain. Her blood pressure well controlled, and his dizziness and headache remained. was measured at 150/110 mm Hg. She had also developed Six years before the current presentation, the patient paroxysmal convulsions; when her eyes turned upward, her visited our department because his workmates had developed limbs twitched and consciousness was lost. These symptoms similar symptoms of dizziness and headache and were were relieved several minutes after onset and occurred rediagnosed with mercury poisoning. The patient’s blood peatedly more than 10 times every day. The patient also had pressure was 230/180 mm Hg, and his urinary mercury blurred vision and progressive exacerbation of visual opacity. level was 131.54 μmol/molCr (reference range, 0.00– She was admitted to several hospitals for treatment, but none 2.25 μmol/molCr). He began regular treatment with intrawere successful. The results of a computed tomography (CT) muscular dimercaptopropane sulfonate (DMPS) at 0.25 g and magnetic resonance imaging (MRI) of the head, performed daily for 3 days. After 2 courses of this mercury removal outside our hospital, were normal. A skin biopsy showed that treatment, his blood pressure substantially decreased, flucthe muscle fibers had lost their angular appearance and that tuating within the range of 100/90 to 140/90 mm Hg; his inflammatory cells were scattered throughout the interstitium. 24-hour urinary mercury excretion decreased from 5503.4 to Her blood potassium level was 2.83 to 3.25 mmol/L (reference 2197.1 μg/d; and his dizziness and headache improved. After range, 3.5–5.5 mmol/L). Her plasma renin activity in the 5 courses of DMPS treatment, he had clinically recovered horizontal and vertical positions was N 12 μg/L.h (reference and had a normal urinary mercury level. range, 0.05–0.79 μg/L.h) and N 12 μg/L.h (reference range, The patient resumed working in the described smelting 0.93–6.56 μg/L.h), respectively. Her blood level of angiotensin workshop after discharge. He was repeatedly admitted to II in the horizontal and vertical positions was 70.9 ng/L our department 3 times within 5 years for mercury poisoning (reference range, 28.2–52.2 ng/L) and 481.0 ng/L (reference characterized by hypertension and an elevated urinary mercury range, 55.3–115.3 ng/L), respectively. Her blood aldosterone level. His hypertension quickly normalized after each chelalevel in the horizontal and vertical positions was 232.1 ng/L tion treatment. One month before admission, the patient (reference range, 48.5–123.5 ng/L) and 285.2 ng/L (reference presented with recurrence of dizziness but no other abnormalities such as insomnia, hand fibrillation, or oral ulceration. His blood pressure was 150/90 mm Hg and his urinary mercury level was elevated at 12.676 μmol/molCr. Physical examination revealed no other abnormalities and normal vital signs. He had clear consciousness and was in good spirits without scleral yellowing or skin rash. Routine laboratory tests showed normal blood and urine parameters. His 24hour urinary mercury excretion was 208.2 μg/d (reference Figure 1 Changes in urinary mercury level and blood pressure range, 0.0–45.0 μg/d), and his blood mercury level was in Case 1. With the decrease of urinary mercury concentration, 0.002 mg/L (reference range, 0.000–0.015 mg/L). the patient’s blood pressure quickly normalized. C= course of The patient was treated with intramuscular DMPS at 0.25 g chelation treatment; DBP= diastolic blood pressure; SBP= daily for 3 days. His urinary mercury excretions on the first systolic blood pressure; UMC= urinary mercury 3 days after one course of chelation treatment were 502.4, concentration. 208.2, and 102.5 μg/d, respectively. After 2 courses of
. .
ARTICLE IN PRESS Yan et al
Mercury Poisoning With Hypertension
range, 63.0–239.6 ng/L), respectively. Her levels of β2microglobulin in urine and blood were 495.7 mg/L and 1557.5 ng/ml, respectively. Upon admission to our department, the patient’s blood pressure was 150/90 mm Hg and her heart rate was 118 beats/min. The skin on her hands, wrists, legs, and feet was red, hot, and rough with signs of scratching. Neurological examination showed no abnormalities. Toxicologic analysis revealed that her urinary mercury level was 0.171 mg/L (reference range, 0.000–0.010 mg/L) before chelation treatment and 1.408 mg/L after chelation treatment. She had normal urinary lead and arsenic levels. On further inquiry regarding her medical history, we found that the patient and her classmates had long played with mercury pearls on their palms in their classroom. Additional investigation revealed mercury poisoning in dozens of her classmates and teachers. The patient was treated with 5 courses of intramuscular DMPS (0.125 g daily for 3 days) as well as symptomatic treatment until her urinary mercury level was normal. After 2 courses of chelation treatment, her blood pressure quickly dropped to normal without the use of antihypertensive drugs, her convulsions disappeared, and her skin rash improved.
3 enzyme activity and increased RAS activation.4 In Case 2, we also found increased blood levels of renin, angiotensin, and aldosterone, suggesting that activation of the RAS is one mechanism of the occurrence and development of hypertension. In addition, some studies have suggested that the potential mechanisms of mercury-related hypertension are increased oxidative stress,1 promotion of free radical stress and lipid peroxidation,5,6 inactivation of paraoxonase,6 endothelial dysfunction,6 and inhibited activation of nuclear factor-κB.1 Hypertension secondary to mercury poisoning often leads to misdiagnosis and delay of appropriate treatment.7 We suggest that the possibility of mercury poisoning should be excluded in the diagnosis and treatment of unknown hypertension with a history of toxic exposure.
CONCLUSIONS Mercury poisoning can present either with hypertension as the main sign or together with multiorgan damage. RAS activation may be involved in the occurrence and development of hypertension. After chelation treatment, the hypertension secondary to mercury poisoning rapidly resolves.
DISCUSSION Rare reports have described mercury poisoning that clinically manifested as hypertension. Our report shows that mercury poisoning can present mainly as hypertension as seen in Case 1 or as hypertension accompanied by serious symptoms as seen in Case 2. The characteristics of hypertension secondary to mercury poisoning as seen in our patients can be summarized as follows: 1) the hypertension can rapidly normalize after mercury removal treatment and recur after reexposure to mercury; 2) the elevated blood levels of renin, angiotensin, and aldosterone in Case 2 indicate that the renin-angiotensin system (RAS) may be involved in the occurrence and development of hypertension; and 3) the prognosis of hypertension secondary to mercury poisoning is good. The mechanisms of mercury toxicity involving the cardiovascular system have not been fully elucidated.3 Mercury exposure reportedly leads to increased angiotensin-converting
References 1. Virtanen JK, Rissanen TH, Voutilainen S, et al. Mercury as a risk factor for cardiovascular diseases. J Nutr Biochem 2007;18(2):75-85. 2. Wang HB, Niu WK. Diagnosis and treatment of mercury poisoning. Chinese J Ind Med 2009;18(3):238-41. 3. Wildemann TM, Siciliano SD, Weber LP. The mechanisms associated with the development of hypertension after exposure to lead, mercury species or their mixtures differs with the metal and the mixture ratio. Toxicology 2016;339:1-8. 4. Rizzetti DA, Da ST, Escobar AG, et al. Mercury-induced vascular dysfunction is mediated by angiotensin II AT-1 receptor upregulation. Environ Res 2018;162:287-96. 5. Zalups RK. Molecular interactions with mercury in the kidney. Pharmacol Rev 2000;52(1):113-43. 6. Fernandes AB, Barros FL, Pecanha FM, et al. Toxic effects of mercury on the cardiovascular and central nervous systems. J Biomed Biotechnol 2012;2012, 949048. 7. Gao Z, Ying X, Yan J, et al. Acute mercury vapor poisoning in a 3-monthold infant: A case report. Clin Chim Acta 2017;465:119-112.