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Cardiac and Renal Effects of Atrasentan in Combination with Enalapril and Paricalcitol in Uremic Rats

BACKGROUND/AIMS: The search for new therapies providing cardiorenal protection in chronic kidney disease (CKD) has led to treatments that combine conventional renin-angiotensin-aldosterone-system inhibitors with other drugs that exhibit potential in disease management. METHODS: In rats made uremic b...

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Autores principales: Ritter, Cynthia, Zhang, Sarah, Finch, Jane L., Liapis, Helen, Suarez, Edu, Ferder, Leon, Delmez, James, Slatopolsky, Eduardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225010/
https://www.ncbi.nlm.nih.gov/pubmed/25300759
http://dx.doi.org/10.1159/000355811
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author Ritter, Cynthia
Zhang, Sarah
Finch, Jane L.
Liapis, Helen
Suarez, Edu
Ferder, Leon
Delmez, James
Slatopolsky, Eduardo
author_facet Ritter, Cynthia
Zhang, Sarah
Finch, Jane L.
Liapis, Helen
Suarez, Edu
Ferder, Leon
Delmez, James
Slatopolsky, Eduardo
author_sort Ritter, Cynthia
collection PubMed
description BACKGROUND/AIMS: The search for new therapies providing cardiorenal protection in chronic kidney disease (CKD) has led to treatments that combine conventional renin-angiotensin-aldosterone-system inhibitors with other drugs that exhibit potential in disease management. METHODS: In rats made uremic by renal ablation, we examined the effects of addition of the endothelin-A receptor antagonist atrasentan to a previously examined combination of enalapril (angiotensin converting enzyme inhibitor) and paricalcitol (vitamin D receptor activator) on cardiac and renal parameters. The effects of the individual and combined drugs were examined after a 3-month treatment. RESULTS: A decrease in systolic blood pressure, serum creatinine and proteinuria, and improvement of renal histology in uremic rats were attributed to enalapril and/or paricalcitol treatment; atrasentan alone had no effect. In heart tissue, individual treatment with the drugs blunted the increase in cardiomyocyte size, and combined treatment additively decreased cardiomyocyte size to normal levels. Perivascular fbrosis was blunted in uremic control rats with atrasentan or enalapril treatment. CONCLUSIONS: We found distinct cardiac and renal effects of atrasentan. Combination treatment with atrasentan, enalapril and paricalcitol provided positive effects on cardiac remodeling in uremic rats, whereas combination treatment did not offer further protective effects on blood pressure, proteinuria or renal histology.
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spelling pubmed-42250102015-09-19 Cardiac and Renal Effects of Atrasentan in Combination with Enalapril and Paricalcitol in Uremic Rats Ritter, Cynthia Zhang, Sarah Finch, Jane L. Liapis, Helen Suarez, Edu Ferder, Leon Delmez, James Slatopolsky, Eduardo Kidney Blood Press Res Article BACKGROUND/AIMS: The search for new therapies providing cardiorenal protection in chronic kidney disease (CKD) has led to treatments that combine conventional renin-angiotensin-aldosterone-system inhibitors with other drugs that exhibit potential in disease management. METHODS: In rats made uremic by renal ablation, we examined the effects of addition of the endothelin-A receptor antagonist atrasentan to a previously examined combination of enalapril (angiotensin converting enzyme inhibitor) and paricalcitol (vitamin D receptor activator) on cardiac and renal parameters. The effects of the individual and combined drugs were examined after a 3-month treatment. RESULTS: A decrease in systolic blood pressure, serum creatinine and proteinuria, and improvement of renal histology in uremic rats were attributed to enalapril and/or paricalcitol treatment; atrasentan alone had no effect. In heart tissue, individual treatment with the drugs blunted the increase in cardiomyocyte size, and combined treatment additively decreased cardiomyocyte size to normal levels. Perivascular fbrosis was blunted in uremic control rats with atrasentan or enalapril treatment. CONCLUSIONS: We found distinct cardiac and renal effects of atrasentan. Combination treatment with atrasentan, enalapril and paricalcitol provided positive effects on cardiac remodeling in uremic rats, whereas combination treatment did not offer further protective effects on blood pressure, proteinuria or renal histology. 2014-09-19 2014 /pmc/articles/PMC4225010/ /pubmed/25300759 http://dx.doi.org/10.1159/000355811 Text en Copyright © 2014 S. Karger AG, Basel http://creativecommons.org/licenses/by/2.0/%22 This is an Open Access article licensed under the terms of the Creative Commons Attribution- NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license (http://www.karger.com/OA-license) ), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
spellingShingle Article
Ritter, Cynthia
Zhang, Sarah
Finch, Jane L.
Liapis, Helen
Suarez, Edu
Ferder, Leon
Delmez, James
Slatopolsky, Eduardo
Cardiac and Renal Effects of Atrasentan in Combination with Enalapril and Paricalcitol in Uremic Rats
title Cardiac and Renal Effects of Atrasentan in Combination with Enalapril and Paricalcitol in Uremic Rats
title_full Cardiac and Renal Effects of Atrasentan in Combination with Enalapril and Paricalcitol in Uremic Rats
title_fullStr Cardiac and Renal Effects of Atrasentan in Combination with Enalapril and Paricalcitol in Uremic Rats
title_full_unstemmed Cardiac and Renal Effects of Atrasentan in Combination with Enalapril and Paricalcitol in Uremic Rats
title_short Cardiac and Renal Effects of Atrasentan in Combination with Enalapril and Paricalcitol in Uremic Rats
title_sort cardiac and renal effects of atrasentan in combination with enalapril and paricalcitol in uremic rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225010/
https://www.ncbi.nlm.nih.gov/pubmed/25300759
http://dx.doi.org/10.1159/000355811
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