Kinin B1 receptor antagonism is equally efficient as angiotensin receptor 1 antagonism in reducing renal fibrosis in experimental obstructive nephropathy, but is not additive.
Background: Renal tubulointerstitial fibrosis is the pathological hallmark of chronic kidney disease. Currently, inhibitors of the renin angiotensin system (RAS) remain the sole therapy in human displaying antifibrotic properties. Further antifibrotic molecules are needed. We have recently reported...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00008/full |
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| author | Antoine eHuart Antoine eHuart Julie eKlein Julie eKlein Julien eGonzalez Julien eGonzalez Bénedicte eBuffin-Meyer Bénedicte eBuffin-Meyer Eric eNeau Eric eNeau Christine eDelage Christine eDelage Denis eCalise David eRibes David eRibes Joost-Peter eSchanstra Joost-Peter eSchanstra Jean-Loup eBascands Jean-Loup eBascands |
| author_facet | Antoine eHuart Antoine eHuart Julie eKlein Julie eKlein Julien eGonzalez Julien eGonzalez Bénedicte eBuffin-Meyer Bénedicte eBuffin-Meyer Eric eNeau Eric eNeau Christine eDelage Christine eDelage Denis eCalise David eRibes David eRibes Joost-Peter eSchanstra Joost-Peter eSchanstra Jean-Loup eBascands Jean-Loup eBascands |
| author_sort | Antoine eHuart |
| collection | DOAJ |
| description | Background: Renal tubulointerstitial fibrosis is the pathological hallmark of chronic kidney disease. Currently, inhibitors of the renin angiotensin system (RAS) remain the sole therapy in human displaying antifibrotic properties. Further antifibrotic molecules are needed. We have recently reported that the delayed blockade of the bradykinin B1 receptor (B1R) reduced the development of fibrosis in two animal models of renal fibrosis. The usefulness of new drugs also resides in outperforming the gold standards and eventually being additive or complementary to existing therapies. Methods: In this study we compared the efficacy of a B1R antagonist (B1Ra) with that of an angiotensin type 1 receptor antagonist (AT1a) in the unilateral ureteral obstruction (UUO) model of renal fibrosis and determined whether bi-therapy presented higher efficacy than any of the drugs alone. Results: B1R antagonism was as efficient as the gold-standard AT1a treatment. However bitherapy did not improve the antifibrotic effects at the protein level. We sought for the reason of the absence of this additive effect by studying the expression of a panel of genes involved in the fibrotic process. Interestingly, at the molecular level the different drugs targeted different players of fibrosis that, however, in this severe model did not result in improved reduction of fibrosis at the protein level. Conclusions: As the B1R is induced specifically in the diseased organ and thus potentially displays low side effects it might be an interesting alternative in cases of poor tolerability to RAS inhibitors. |
| first_indexed | 2024-12-21T21:41:43Z |
| format | Article |
| id | doaj.art-4e17297176794fe3b66062edb954e217 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-21T21:41:43Z |
| publishDate | 2015-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-4e17297176794fe3b66062edb954e2172022-12-21T18:49:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122015-02-01610.3389/fphar.2015.00008121494Kinin B1 receptor antagonism is equally efficient as angiotensin receptor 1 antagonism in reducing renal fibrosis in experimental obstructive nephropathy, but is not additive.Antoine eHuart0Antoine eHuart1Julie eKlein2Julie eKlein3Julien eGonzalez4Julien eGonzalez5Bénedicte eBuffin-Meyer6Bénedicte eBuffin-Meyer7Eric eNeau8Eric eNeau9Christine eDelage10Christine eDelage11Denis eCalise12David eRibes13David eRibes14Joost-Peter eSchanstra15Joost-Peter eSchanstra16Jean-Loup eBascands17Jean-Loup eBascands18CHU-RangueilUniversité Toulouse III Paul-SabatierInserm U1048- Institut of Cardiovascular and Metabolic DiseaseUniversité Toulouse III Paul-SabatierInserm U1048- Institut of Cardiovascular and Metabolic DiseaseUniversité Toulouse III Paul-SabatierInserm U1048- Institut of Cardiovascular and Metabolic DiseaseUniversité Toulouse III Paul-SabatierInserm U1048- Institut of Cardiovascular and Metabolic DiseaseUniversité Toulouse III Paul-SabatierInserm U1048- Institut of Cardiovascular and Metabolic DiseaseUniversité Toulouse III Paul-SabatierUniversité Toulouse III Paul-SabatierCHU-RangueilUniversité Toulouse III Paul-SabatierInserm U1048- Institut of Cardiovascular and Metabolic DiseaseUniversité Toulouse III Paul-SabatierInserm U1048- Institut of Cardiovascular and Metabolic DiseaseUniversité Toulouse III Paul-SabatierBackground: Renal tubulointerstitial fibrosis is the pathological hallmark of chronic kidney disease. Currently, inhibitors of the renin angiotensin system (RAS) remain the sole therapy in human displaying antifibrotic properties. Further antifibrotic molecules are needed. We have recently reported that the delayed blockade of the bradykinin B1 receptor (B1R) reduced the development of fibrosis in two animal models of renal fibrosis. The usefulness of new drugs also resides in outperforming the gold standards and eventually being additive or complementary to existing therapies. Methods: In this study we compared the efficacy of a B1R antagonist (B1Ra) with that of an angiotensin type 1 receptor antagonist (AT1a) in the unilateral ureteral obstruction (UUO) model of renal fibrosis and determined whether bi-therapy presented higher efficacy than any of the drugs alone. Results: B1R antagonism was as efficient as the gold-standard AT1a treatment. However bitherapy did not improve the antifibrotic effects at the protein level. We sought for the reason of the absence of this additive effect by studying the expression of a panel of genes involved in the fibrotic process. Interestingly, at the molecular level the different drugs targeted different players of fibrosis that, however, in this severe model did not result in improved reduction of fibrosis at the protein level. Conclusions: As the B1R is induced specifically in the diseased organ and thus potentially displays low side effects it might be an interesting alternative in cases of poor tolerability to RAS inhibitors.http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00008/fullcombined therapyBradykinin B1 receptorAngiotensin receptor inhibitionlow density arrayrenal fibrosis. |
| spellingShingle | Antoine eHuart Antoine eHuart Julie eKlein Julie eKlein Julien eGonzalez Julien eGonzalez Bénedicte eBuffin-Meyer Bénedicte eBuffin-Meyer Eric eNeau Eric eNeau Christine eDelage Christine eDelage Denis eCalise David eRibes David eRibes Joost-Peter eSchanstra Joost-Peter eSchanstra Jean-Loup eBascands Jean-Loup eBascands Kinin B1 receptor antagonism is equally efficient as angiotensin receptor 1 antagonism in reducing renal fibrosis in experimental obstructive nephropathy, but is not additive. Frontiers in Pharmacology combined therapy Bradykinin B1 receptor Angiotensin receptor inhibition low density array renal fibrosis. |
| title | Kinin B1 receptor antagonism is equally efficient as angiotensin receptor 1 antagonism in reducing renal fibrosis in experimental obstructive nephropathy, but is not additive. |
| title_full | Kinin B1 receptor antagonism is equally efficient as angiotensin receptor 1 antagonism in reducing renal fibrosis in experimental obstructive nephropathy, but is not additive. |
| title_fullStr | Kinin B1 receptor antagonism is equally efficient as angiotensin receptor 1 antagonism in reducing renal fibrosis in experimental obstructive nephropathy, but is not additive. |
| title_full_unstemmed | Kinin B1 receptor antagonism is equally efficient as angiotensin receptor 1 antagonism in reducing renal fibrosis in experimental obstructive nephropathy, but is not additive. |
| title_short | Kinin B1 receptor antagonism is equally efficient as angiotensin receptor 1 antagonism in reducing renal fibrosis in experimental obstructive nephropathy, but is not additive. |
| title_sort | kinin b1 receptor antagonism is equally efficient as angiotensin receptor 1 antagonism in reducing renal fibrosis in experimental obstructive nephropathy but is not additive |
| topic | combined therapy Bradykinin B1 receptor Angiotensin receptor inhibition low density array renal fibrosis. |
| url | http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00008/full |
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