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

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

Author Caires, A. Autor UNIFESP Google Scholar
Fernandes, G. S. Autor UNIFESP Google Scholar
Leme, A. M. Autor UNIFESP Google Scholar
Castino, B. Google Scholar
Pessoa, E. A. Autor UNIFESP Google Scholar
Fernandes, S. M. Google Scholar
Fonseca, C. D. Autor UNIFESP Google Scholar
Vattimo, M. F. Google Scholar
Schor, N. Autor UNIFESP Google Scholar
Borges, F. T. Autor UNIFESP Google Scholar
Abstract 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.
Keywords Genetically hypertensive rats
Acute kidney injury
Cyclosporine-A
Bosentan
Macitentan
Endothelin-1
xmlui.dri2xhtml.METS-1.0.item-coverage Sao Paulo
Language English
Date 2018
Published in Brazilian Journal Of Medical And Biological Research. Sao Paulo, v. 51, n. 2, p. -, 2018.
ISSN 0100-879X (Sherpa/Romeo, impact factor)
Publisher Assoc Bras Divulg Cientifica
Extent -
Origin http://dx.doi.org/10.1590/1414-431X20176373
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000417680600001
URI https://repositorio.unifesp.br/handle/11600/53967

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