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Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Associação Brasileira de Divulgação Científica
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731326/ https://www.ncbi.nlm.nih.gov/pubmed/29267497 http://dx.doi.org/10.1590/1414-431X20176373 |
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author | Caires, A. Fernandes, G.S. Leme, A.M. Castino, B. Pessoa, E.A. Fernandes, S.M. Fonseca, C.D. Vattimo, M.F. Schor, N. Borges, F.T. |
author_facet | Caires, A. Fernandes, G.S. Leme, A.M. Castino, B. Pessoa, E.A. Fernandes, S.M. Fonseca, C.D. Vattimo, M.F. Schor, N. Borges, F.T. |
author_sort | Caires, A. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-5731326 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Associação Brasileira de Divulgação Científica |
record_format | MEDLINE/PubMed |
spelling | pubmed-57313262017-12-28 Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats Caires, A. Fernandes, G.S. Leme, A.M. Castino, B. Pessoa, E.A. Fernandes, S.M. Fonseca, C.D. Vattimo, M.F. Schor, N. Borges, F.T. Braz J Med Biol Res Research Articles 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. Associação Brasileira de Divulgação Científica 2017-12-11 /pmc/articles/PMC5731326/ /pubmed/29267497 http://dx.doi.org/10.1590/1414-431X20176373 Text en https://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Caires, A. Fernandes, G.S. Leme, A.M. Castino, B. Pessoa, E.A. Fernandes, S.M. Fonseca, C.D. Vattimo, M.F. Schor, N. Borges, F.T. 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 |
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_short | 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 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731326/ https://www.ncbi.nlm.nih.gov/pubmed/29267497 http://dx.doi.org/10.1590/1414-431X20176373 |
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