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A growing number of studies show an association between lead or mercury exposure and cardiovascular effects. We investigated the cardiovascular effects of single metal exposure or co\u2010exposure to methylmercury [MeHg(I)], inorganic mercury [Hg(II)] and lead [Pb(II)]. Male Wistar rats received four different metal mixtures for 28\u2009days through the drinking water. The ratios of the metals were based on reference and environmental exposure values. Blood and pulse pressure, cardiac output and electrical activity of the heart were selected as end\u2010points. While exposure to only MeHg(I) increased the systolic blood pressure and decreased cardiac output, the effects were reversed with combined exposures (antagonism). In contrast to these effects, combined exposures negatively affected the electrical activity of the heart (synergism). Thus, it appears that estimates of blood total Hg levels need to be paired with estimates of what species of mercury dominate exposure as well as whether lead co\u2010exposure is present to link total blood Hg levels to cardiovascular effects. Based on current human exposure data and our results, there may be an increased risk of cardiac events as a result of combined exposures to Hg(II), MeHg(I) and Pb(II). This increased risk needs to be clarified by analyzing lead and Hg exposure data in relation to cardiac electrical activity in epidemiological studies. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3092","type":"journal-article","created":{"date-parts":[[2014,12,19]],"date-time":"2014-12-19T05:30:20Z","timestamp":1418967020000},"page":"918-926","source":"Crossref","is-referenced-by-count":35,"title":["Combined exposure to lead, inorganic mercury and methylmercury shows deviation from additivity for cardiovascular toxicity in rats"],"prefix":"10.1002","volume":"35","author":[{"given":"Tanja M.","family":"Wildemann","sequence":"first","affiliation":[{"name":"Toxicology Graduate Program University of Saskatchewan  44 Campus Drive Saskatoon SK Canada S7N 5B3"},{"name":"Department of Soil Science University of Saskatchewan  51 Campus Drive Saskatoon SK Canada S7N 5A8"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn P.","family":"Weber","sequence":"additional","affiliation":[{"name":"Toxicology Graduate Program University of Saskatchewan  44 Campus Drive Saskatoon SK Canada S7N 5B3"},{"name":"Department of Veterinary Biomedical Sciences University of Saskatchewan  52 Campus Drive Saskatoon SK Canada S7N 5B4"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven D.","family":"Siciliano","sequence":"additional","affiliation":[{"name":"Toxicology Graduate Program University of Saskatchewan  44 Campus Drive Saskatoon SK Canada S7N 5B3"},{"name":"Department of Soil Science University of Saskatchewan  51 Campus Drive Saskatoon SK Canada S7N 5A8"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,12,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0810823"},{"key":"e_1_2_8_3_1","unstructured":"ATSDR (Agency for Toxic Substances and Disease Registry).2007.Toxicological Profile for Lead ATSDR:Atlanta Georgia US."},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.56.651.1"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.02110s5689"},{"key":"e_1_2_8_6_1","first-page":"250","article-title":"Association of blood and hair mercury with blood pressure and vascular reactivity","volume":"108","author":"Bautista LE","year":"2009","journal-title":"WMJ"},{"key":"e_1_2_8_7_1","volume-title":"Veterinary Echocardiography","author":"Boon JA","year":"2011"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1103828"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2004.09.007"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/03610928908830065"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10651-005-5687-x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(98)00402-0"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajim.20476"},{"key":"e_1_2_8_14_1","first-page":"2831","article-title":"Lead dietary exposure in the European population","volume":"10","author":"EFSA (European Food Safety Authority)","year":"2012","journal-title":"EFSA J."},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2012.2985"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2007.06.036"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1003279"},{"key":"e_1_2_8_18_1","first-page":"132","article-title":"Sixty\u2010first report of the Joint FAO\/WHO Expert Committee on Food Additives","volume":"922","author":"FAO\/WHO (Food and Agriculture Organization of the United Nations\/World Health Organization)","year":"2004","journal-title":"WHO Technical Report Series"},{"key":"e_1_2_8_19_1","first-page":"605","article-title":"Safety evaluation of certain food additives and contaminants","volume":"63","author":"FAO\/WHO (Food and Agriculture Organization of the United Nations\/World Health Organization)","year":"2011","journal-title":"WHO Food Additives Series"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2011.05.001"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-069X-5-29"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(98)00011-3"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/15287390802240918"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-200301000-00011"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijheh.2012.03.001"},{"key":"e_1_2_8_26_1","doi-asserted-by":"crossref","unstructured":"HaraA ThijsL AsayamaK GuY\u2010M JacobsL ZhangZ\u2010Y LiuY\u2010P NawrotTS StaessenJA.2014.Blood pressure in relation to environmental lead exposure in the National Health and Nutrition Examination Survey 2003 to 2010. 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