title: Cardiovascular responses to lead are biphasic, while methylmercury, but not inorganic mercury, monotonically increases blood pressure in rats.
abstract: Cardiovascular diseases, such as heart attack and stroke, are the major cause of death worldwide. It is well known that a high number of environmental and physiological risk factors contribute to the development of cardiovascular diseases. Although risk factors are additive, increased blood pressure (hypertension) is the greatest risk factor. Over the last two decades, a growing number of epidemiological studies associate environmental exposure to lead or mercury species with hypertension. However, cardiovascular effects beyond blood pressure are rarely studied and thresholds for effect are not yet clear. To explore effects of lead or mercury species on the cardiovascular system, normal male Wistar rats were exposed to a range of doses of lead, inorganic mercury or methylmercury through the drinking water for four weeks. High-resolution ultrasound was used to measure heart and vascular function (carotid artery blood flow) at baseline and at the end of the exposure, while blood pressure was measured directly in the femoral artery at the end of the 4-week exposure. After 4 weeks, blood pressure responses to lead were biphasic. Low lead levels decreased blood pressure, dilated the carotid artery and increased cardiac output. At higher lead doses, rats had increased blood pressure. In contrast, methylmercury-exposed rats had increased blood pressure at all doses despite dilated carotid arteries. Inorganic mercury did not show any significant cardiovascular effects. Based on the current study, the benchmark dose level 10% (BMDL10s) for systolic blood pressure for lead, inorganic mercury and methylmercury are 1.1, 1.3 and 1.0 μg/kg-bw/d, respectively. However, similar total mercury blood levels attributed to inorganic mercury or methylmercury produced strikingly different results with inorganic mercury having no observable effect on the cardiovascular system but methylmercury increasing systolic and pulse pressures. Therefore, adverse cardiovascular effects cannot be predicted by total blood mercury level alone and the mercury species of exposure must be taken into account.
authors.affiliation: Toxicology Graduate Program, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK S7N 5B3, Canada; Department of Soil Science, University of Saskatchewan, 51 Campus Drive, Saskatoon, SK S7N 5A8, Canada. Electronic address: tanja.wildemann@usask.ca.
authors.forename: Tanja M
authors.initials: TM
authors.lastname: Wildemann
authors.affiliation: Department of Veterinary Biomedical Sciences, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada. Electronic address: n.mir@usask.ca.
authors.forename: Naghmeh
authors.initials: N
authors.lastname: Mirhosseini
authors.affiliation: Toxicology Graduate Program, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK S7N 5B3, Canada; Department of Soil Science, University of Saskatchewan, 51 Campus Drive, Saskatoon, SK S7N 5A8, Canada. Electronic address: steven.siciliano@usask.ca.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Siciliano
authors.affiliation: Toxicology Graduate Program, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK S7N 5B3, Canada; Department of Veterinary Biomedical Sciences, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada. Electronic address: lynn.weber@usask.ca.
authors.forename: Lynn P
authors.initials: LP
authors.lastname: Weber
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D002319:Cardiovascular System / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005263:Femoral Artery / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008627:Mercuric Chloride / Q000097:blood / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000097:blood / Q000633:toxicity*; D009942:Organometallic Compounds / Q000097:blood / Q000633:toxicity*; D017208:Rats, Wistar; D018570:Risk Assessment; D013997:Time Factors; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects
chemical_list: D008767:Methylmercury Compounds; D009942:Organometallic Compounds; D008627:Mercuric Chloride; C004925:methylmercuric chloride; C008261:lead acetate
keywords: Blood pressure; Cardiovascular; Lead acetate; Mercury chloride; Mono-methylmercury chloride; Rats