Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats

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dc.citation.issue2
dc.citation.volume51
dc.contributor.authorCaires, A. [UNIFESP]
dc.contributor.authorFernandes, G. S. [UNIFESP]
dc.contributor.authorLeme, A. M. [UNIFESP]
dc.contributor.authorCastino, B.
dc.contributor.authorPessoa, E. A. [UNIFESP]
dc.contributor.authorFernandes, S. M.
dc.contributor.authorFonseca, C. D. [UNIFESP]
dc.contributor.authorVattimo, M. F.
dc.contributor.authorSchor, N. [UNIFESP]
dc.contributor.authorBorges, F. T. [UNIFESP]
dc.coverageSao Paulo
dc.date.accessioned2020-07-02T18:52:14Z
dc.date.available2020-07-02T18:52:14Z
dc.date.issued2018
dc.description.abstractCyclosporin-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.en
dc.description.affiliationUniv Fed Sao Paulo, Disciplina Nefrol, Dept Med, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Cruzeiro Sul, Programa Interdisciplinar Ciencias Saude, Inst Ciencias Atividade Fis & Esporte, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Sao Paulo, LEMA, Escola Enfermagem, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Enfermagem Clin & Cirurg, Escola Paulista Enfermagem, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Disciplina Nefrol, Dept Med, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Enfermagem Clin & Cirurg, Escola Paulista Enfermagem, Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1590/1414-431X20176373
dc.identifier.citationBrazilian Journal Of Medical And Biological Research. Sao Paulo, v. 51, n. 2, p. -, 2018.
dc.identifier.doi10.1590/1414-431X20176373
dc.identifier.fileWOS000417680600001.pdf
dc.identifier.issn0100-879X
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/53967
dc.identifier.wosWOS:000417680600001
dc.language.isoeng
dc.publisherAssoc Bras Divulg Cientifica
dc.relation.ispartofBrazilian Journal Of Medical And Biological Research
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectGenetically hypertensive ratsen
dc.subjectAcute kidney injuryen
dc.subjectCyclosporine-Aen
dc.subjectBosentanen
dc.subjectMacitentanen
dc.subjectEndothelin-1en
dc.titleEndothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive ratsen
dc.typeinfo:eu-repo/semantics/article
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