Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/handle/11600/53967 http://dx.doi.org/10.1590/1414-431X20176373 |
Resumo: | Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects. |
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Caires, A. [UNIFESP]Fernandes, G. S. [UNIFESP]Leme, A. M. [UNIFESP]Castino, B.Pessoa, E. A. [UNIFESP]Fernandes, S. M.Fonseca, C. D. [UNIFESP]Vattimo, M. F.Schor, N. [UNIFESP]Borges, F. T. [UNIFESP]2020-07-02T18:52:14Z2020-07-02T18:52:14Z2018Brazilian Journal Of Medical And Biological Research. Sao Paulo, v. 51, n. 2, p. -, 2018.0100-879Xhttps://repositorio.unifesp.br/handle/11600/53967http://dx.doi.org/10.1590/1414-431X20176373WOS000417680600001.pdf10.1590/1414-431X20176373WOS:000417680600001Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.Univ Fed Sao Paulo, Disciplina Nefrol, Dept Med, Sao Paulo, SP, BrazilUniv Cruzeiro Sul, Programa Interdisciplinar Ciencias Saude, Inst Ciencias Atividade Fis & Esporte, Sao Paulo, SP, BrazilUniv Sao Paulo, LEMA, Escola Enfermagem, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Enfermagem Clin & Cirurg, Escola Paulista Enfermagem, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Disciplina Nefrol, Dept Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Enfermagem Clin & Cirurg, Escola Paulista Enfermagem, Sao Paulo, SP, BrazilWeb of Science-engAssoc Bras Divulg CientificaBrazilian Journal Of Medical And Biological ResearchGenetically hypertensive ratsAcute kidney injuryCyclosporine-ABosentanMacitentanEndothelin-1Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleSao Paulo512info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000417680600001.pdfapplication/pdf1564324${dspace.ui.url}/bitstream/11600/53967/1/WOS000417680600001.pdf57c71f6c13e994b01f7b29e339cc3c49MD51open accessTEXTWOS000417680600001.pdf.txtWOS000417680600001.pdf.txtExtracted texttext/plain34816${dspace.ui.url}/bitstream/11600/53967/2/WOS000417680600001.pdf.txtd27726c5a5fbccc7272c625096d0c11fMD52open accessTHUMBNAILWOS000417680600001.pdf.jpgWOS000417680600001.pdf.jpgIM Thumbnailimage/jpeg7357${dspace.ui.url}/bitstream/11600/53967/4/WOS000417680600001.pdf.jpgf7419fa15551bc0f604851401c071a82MD54open access11600/539672022-08-01 08:32:00.146open accessoai:repositorio.unifesp.br:11600/53967Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-08-01T11:32Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats |
title |
Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats |
spellingShingle |
Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats Caires, A. [UNIFESP] Genetically hypertensive rats Acute kidney injury Cyclosporine-A Bosentan Macitentan Endothelin-1 |
title_short |
Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats |
title_full |
Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats |
title_fullStr |
Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats |
title_full_unstemmed |
Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats |
title_sort |
Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats |
author |
Caires, A. [UNIFESP] |
author_facet |
Caires, A. [UNIFESP] Fernandes, G. S. [UNIFESP] Leme, A. M. [UNIFESP] Castino, B. Pessoa, E. A. [UNIFESP] Fernandes, S. M. Fonseca, C. D. [UNIFESP] Vattimo, M. F. Schor, N. [UNIFESP] Borges, F. T. [UNIFESP] |
author_role |
author |
author2 |
Fernandes, G. S. [UNIFESP] Leme, A. M. [UNIFESP] Castino, B. Pessoa, E. A. [UNIFESP] Fernandes, S. M. Fonseca, C. D. [UNIFESP] Vattimo, M. F. Schor, N. [UNIFESP] Borges, F. T. [UNIFESP] |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Caires, A. [UNIFESP] Fernandes, G. S. [UNIFESP] Leme, A. M. [UNIFESP] Castino, B. Pessoa, E. A. [UNIFESP] Fernandes, S. M. Fonseca, C. D. [UNIFESP] Vattimo, M. F. Schor, N. [UNIFESP] Borges, F. T. [UNIFESP] |
dc.subject.eng.fl_str_mv |
Genetically hypertensive rats Acute kidney injury Cyclosporine-A Bosentan Macitentan Endothelin-1 |
topic |
Genetically hypertensive rats Acute kidney injury Cyclosporine-A Bosentan Macitentan Endothelin-1 |
description |
Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018 |
dc.date.accessioned.fl_str_mv |
2020-07-02T18:52:14Z |
dc.date.available.fl_str_mv |
2020-07-02T18:52:14Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Brazilian Journal Of Medical And Biological Research. Sao Paulo, v. 51, n. 2, p. -, 2018. |
dc.identifier.uri.fl_str_mv |
https://repositorio.unifesp.br/handle/11600/53967 http://dx.doi.org/10.1590/1414-431X20176373 |
dc.identifier.issn.none.fl_str_mv |
0100-879X |
dc.identifier.file.none.fl_str_mv |
WOS000417680600001.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1590/1414-431X20176373 |
dc.identifier.wos.none.fl_str_mv |
WOS:000417680600001 |
identifier_str_mv |
Brazilian Journal Of Medical And Biological Research. Sao Paulo, v. 51, n. 2, p. -, 2018. 0100-879X WOS000417680600001.pdf 10.1590/1414-431X20176373 WOS:000417680600001 |
url |
https://repositorio.unifesp.br/handle/11600/53967 http://dx.doi.org/10.1590/1414-431X20176373 |
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eng |
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Brazilian Journal Of Medical And Biological Research |
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openAccess |
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- |
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Sao Paulo |
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Assoc Bras Divulg Cientifica |
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Assoc Bras Divulg Cientifica |
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