Cadmium exposure activates NADPH oxidase, renin–angiotensin system and cyclooxygenase 2 pathways in arteries, inducing hypertension and vascular damage
Exposure to high concentrations of cadmium (Cd), widely used in many industries and found in air, food and contaminated water, is not uncommon. Cd damages the cardiovascular system, but the vascular mechanisms involved are not fully understood. This study investigated the mechanisms involved in cardiovascular damage after exposure to high Cd concentrations. Three-month-old male Wistar rats were treated intraperitoneally for 14 days with distilled water (Untreated group) or 1 mg/kg cadmium chloride (Cd group). We investigated the systolic blood pressure (SBP) and vascular reactivity of mesenteric resistance arteries (MRA) and the aorta by analysing contractile and relaxation responses in the absence and presence of the endothelium; we also evaluated pathways involved in vascular tone regulation. Superoxide anion production, COX-2 protein expression and in situ detection of COX-2, AT-1, and NOX-1 were evaluated. Oxidative status, creatinine level and angiotensin-converting enzyme (ACE) activity in plasma were also evaluated. Fourteen-day exposure to a high Cd concentration induced hypertension associated with vascular dysfunction in MRA and the aorta. In both vessels, there was increased participation of cyclooxygenase 2 (COX2), angiotensin II type 1 (AT1) receptor and NOX1. MRA also presented endothelial dysfunction, denoted by impaired acetylcholine-mediated relaxation. All vascular changes were accompanied by increased reactive oxygen species production and COX2, NOX1 and AT1 receptor expression in vascular tissue. Overall, high Cd concentrations induced cardiovascular damage: hypertension, endothelial dysfunction and vascular damage in conductance and resistance arteries, NADPH oxidase, renin–angiotensin system and COX2 pathway activation.
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Elsevier
2020
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Online Access: | http://hdl.handle.net/10261/228542 http://dx.doi.org/10.13039/501100003593 http://dx.doi.org/10.13039/501100002322 http://dx.doi.org/10.13039/501100001807 http://dx.doi.org/10.13039/501100004263 http://dx.doi.org/10.13039/501100010598 http://dx.doi.org/10.13039/501100011033 |
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dig-cial-es-10261-2285422021-04-15T11:39:16Z Cadmium exposure activates NADPH oxidase, renin–angiotensin system and cyclooxygenase 2 pathways in arteries, inducing hypertension and vascular damage Gomes Pinheiro Júnior, José Eudes Zambelli Moraes, Paola Diaz Rodriguez, Marina Ronacher Simões, Maylla Cibin, Francielli Pinton, Simone Barbosa Junior, Fernando Peçanha, Franck Maciel Vassallo, Dalton Valentim Miguel, Marta Wiggers, Giulia Alessandra Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brasil) Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul Universidade Federal do Pampa Fundação de Amparo à Pesquisa do Estado de São Paulo Agencia Estatal de Investigación (España) Ministerio de Ciencia, Innovación y Universidades (España) Exposure to high concentrations of cadmium (Cd), widely used in many industries and found in air, food and contaminated water, is not uncommon. Cd damages the cardiovascular system, but the vascular mechanisms involved are not fully understood. This study investigated the mechanisms involved in cardiovascular damage after exposure to high Cd concentrations. Three-month-old male Wistar rats were treated intraperitoneally for 14 days with distilled water (Untreated group) or 1 mg/kg cadmium chloride (Cd group). We investigated the systolic blood pressure (SBP) and vascular reactivity of mesenteric resistance arteries (MRA) and the aorta by analysing contractile and relaxation responses in the absence and presence of the endothelium; we also evaluated pathways involved in vascular tone regulation. Superoxide anion production, COX-2 protein expression and in situ detection of COX-2, AT-1, and NOX-1 were evaluated. Oxidative status, creatinine level and angiotensin-converting enzyme (ACE) activity in plasma were also evaluated. Fourteen-day exposure to a high Cd concentration induced hypertension associated with vascular dysfunction in MRA and the aorta. In both vessels, there was increased participation of cyclooxygenase 2 (COX2), angiotensin II type 1 (AT1) receptor and NOX1. MRA also presented endothelial dysfunction, denoted by impaired acetylcholine-mediated relaxation. All vascular changes were accompanied by increased reactive oxygen species production and COX2, NOX1 and AT1 receptor expression in vascular tissue. Overall, high Cd concentrations induced cardiovascular damage: hypertension, endothelial dysfunction and vascular damage in conductance and resistance arteries, NADPH oxidase, renin–angiotensin system and COX2 pathway activation. Supported by National Council for Scientific and Technological Development – CNPq [CNPq 307399/2017-6]; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) Fundação de Amparo à Pesquisa do Rio Grande do Sul - FAPERGS/Brazil [PQG:19/2551-0001810-0]; Programa Nacional de Cooperação Acadêmica; Pró-reitoria de Pesquisa - Universidade Federal do Pampa [Nº 20180615102630]; FAPES/CNPq/PRONEX [Nº 80598773] and Spanish Goverment by the Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) [AGL2017-89213]. JEGPJr and PZM were supported by CAPES/Brazil, MDR by FAPERGS/Brazil (Fundação de Amparo à Pesquisa do Rio Grande do Sul). Peer reviewed 2021-02-04T09:50:48Z 2021-02-04T09:50:48Z 2020 artículo http://purl.org/coar/resource_type/c_6501 Toxicology Letters 333: 80-89 (2020) 0378-4274 http://hdl.handle.net/10261/228542 10.1016/j.toxlet.2020.07.027 http://dx.doi.org/10.13039/501100003593 http://dx.doi.org/10.13039/501100002322 http://dx.doi.org/10.13039/501100001807 http://dx.doi.org/10.13039/501100004263 http://dx.doi.org/10.13039/501100010598 http://dx.doi.org/10.13039/501100011033 en #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/AGL2017-89213-R AGL2017-89213-R/AEI/10.13039/501100011033 https://doi.org/10.1016/j.toxlet.2020.07.027 Sí none Elsevier |
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Exposure to high concentrations of cadmium (Cd), widely used in many industries and found in air, food and contaminated water, is not uncommon. Cd damages the cardiovascular system, but the vascular mechanisms involved are not fully understood. This study investigated the mechanisms involved in cardiovascular damage after exposure to high Cd concentrations. Three-month-old male Wistar rats were treated intraperitoneally for 14 days with distilled water (Untreated group) or 1 mg/kg cadmium chloride (Cd group). We investigated the systolic blood pressure (SBP) and vascular reactivity of mesenteric resistance arteries (MRA) and the aorta by analysing contractile and relaxation responses in the absence and presence of the endothelium; we also evaluated pathways involved in vascular tone regulation. Superoxide anion production, COX-2 protein expression and in situ detection of COX-2, AT-1, and NOX-1 were evaluated. Oxidative status, creatinine level and angiotensin-converting enzyme (ACE) activity in plasma were also evaluated. Fourteen-day exposure to a high Cd concentration induced hypertension associated with vascular dysfunction in MRA and the aorta. In both vessels, there was increased participation of cyclooxygenase 2 (COX2), angiotensin II type 1 (AT1) receptor and NOX1. MRA also presented endothelial dysfunction, denoted by impaired acetylcholine-mediated relaxation. All vascular changes were accompanied by increased reactive oxygen species production and COX2, NOX1 and AT1 receptor expression in vascular tissue. Overall, high Cd concentrations induced cardiovascular damage: hypertension, endothelial dysfunction and vascular damage in conductance and resistance arteries, NADPH oxidase, renin–angiotensin system and COX2 pathway activation. |
author2 |
Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil) |
author_facet |
Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil) Gomes Pinheiro Júnior, José Eudes Zambelli Moraes, Paola Diaz Rodriguez, Marina Ronacher Simões, Maylla Cibin, Francielli Pinton, Simone Barbosa Junior, Fernando Peçanha, Franck Maciel Vassallo, Dalton Valentim Miguel, Marta Wiggers, Giulia Alessandra |
format |
artículo |
author |
Gomes Pinheiro Júnior, José Eudes Zambelli Moraes, Paola Diaz Rodriguez, Marina Ronacher Simões, Maylla Cibin, Francielli Pinton, Simone Barbosa Junior, Fernando Peçanha, Franck Maciel Vassallo, Dalton Valentim Miguel, Marta Wiggers, Giulia Alessandra |
spellingShingle |
Gomes Pinheiro Júnior, José Eudes Zambelli Moraes, Paola Diaz Rodriguez, Marina Ronacher Simões, Maylla Cibin, Francielli Pinton, Simone Barbosa Junior, Fernando Peçanha, Franck Maciel Vassallo, Dalton Valentim Miguel, Marta Wiggers, Giulia Alessandra Cadmium exposure activates NADPH oxidase, renin–angiotensin system and cyclooxygenase 2 pathways in arteries, inducing hypertension and vascular damage |
author_sort |
Gomes Pinheiro Júnior, José Eudes |
title |
Cadmium exposure activates NADPH oxidase, renin–angiotensin system and cyclooxygenase 2 pathways in arteries, inducing hypertension and vascular damage |
title_short |
Cadmium exposure activates NADPH oxidase, renin–angiotensin system and cyclooxygenase 2 pathways in arteries, inducing hypertension and vascular damage |
title_full |
Cadmium exposure activates NADPH oxidase, renin–angiotensin system and cyclooxygenase 2 pathways in arteries, inducing hypertension and vascular damage |
title_fullStr |
Cadmium exposure activates NADPH oxidase, renin–angiotensin system and cyclooxygenase 2 pathways in arteries, inducing hypertension and vascular damage |
title_full_unstemmed |
Cadmium exposure activates NADPH oxidase, renin–angiotensin system and cyclooxygenase 2 pathways in arteries, inducing hypertension and vascular damage |
title_sort |
cadmium exposure activates nadph oxidase, renin–angiotensin system and cyclooxygenase 2 pathways in arteries, inducing hypertension and vascular damage |
publisher |
Elsevier |
publishDate |
2020 |
url |
http://hdl.handle.net/10261/228542 http://dx.doi.org/10.13039/501100003593 http://dx.doi.org/10.13039/501100002322 http://dx.doi.org/10.13039/501100001807 http://dx.doi.org/10.13039/501100004263 http://dx.doi.org/10.13039/501100010598 http://dx.doi.org/10.13039/501100011033 |
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