Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1782343446232563712 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4225010 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT rittercynthia cardiacandrenaleffectsofatrasentanincombinationwithenalaprilandparicalcitolinuremicrats AT zhangsarah cardiacandrenaleffectsofatrasentanincombinationwithenalaprilandparicalcitolinuremicrats AT finchjanel cardiacandrenaleffectsofatrasentanincombinationwithenalaprilandparicalcitolinuremicrats AT liapishelen cardiacandrenaleffectsofatrasentanincombinationwithenalaprilandparicalcitolinuremicrats AT suarezedu cardiacandrenaleffectsofatrasentanincombinationwithenalaprilandparicalcitolinuremicrats AT ferderleon cardiacandrenaleffectsofatrasentanincombinationwithenalaprilandparicalcitolinuremicrats AT delmezjames cardiacandrenaleffectsofatrasentanincombinationwithenalaprilandparicalcitolinuremicrats AT slatopolskyeduardo cardiacandrenaleffectsofatrasentanincombinationwithenalaprilandparicalcitolinuremicrats |