Rosiglitazone, a Ligand to PPARγ, Improves Blood Pressure and Vascular Function through Renin-Angiotensin System Regulation
Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPARγ) ligand, has been reported to act as insulin sensitizer and exert cardiovascular actions. In this work, we hypothesized that RGZ exerts a PPARγ–dependent regulation of blood pressure through modulation of angiotensin-conv...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
|
| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2019/1371758 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832550064129572864 |
|---|---|
| author | María Sánchez-Aguilar Luz Ibarra-Lara Leonardo Del Valle-Mondragón María Esther Rubio-Ruiz Alicia G. Aguilar-Navarro Absalom Zamorano-Carrillo Margarita del Carmen Ramírez-Ortega Gustavo Pastelín-Hernández Alicia Sánchez-Mendoza |
| author_facet | María Sánchez-Aguilar Luz Ibarra-Lara Leonardo Del Valle-Mondragón María Esther Rubio-Ruiz Alicia G. Aguilar-Navarro Absalom Zamorano-Carrillo Margarita del Carmen Ramírez-Ortega Gustavo Pastelín-Hernández Alicia Sánchez-Mendoza |
| author_sort | María Sánchez-Aguilar |
| collection | DOAJ |
| description | Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPARγ) ligand, has been reported to act as insulin sensitizer and exert cardiovascular actions. In this work, we hypothesized that RGZ exerts a PPARγ–dependent regulation of blood pressure through modulation of angiotensin-converting enzyme (ACE)-type 2 (ACE2)/angiotensin-(1-7)/angiotensin II type-2 receptor (AT2R) axis in an experimental model of high blood pressure. We carried on experiments in normotensive (Sham) and aortic coarctation (AoCo)-induced hypertensive male Wistar rats. Both sham and AoCo rats were treated 7 days with vehicle (V), RGZ (5 mg/kg/day), or RGZ+BADGE (120 mg/kg/day) post-coarctation. We measured blood pressure and vascular reactivity on aortic rings, as well as the expression of renin-angiotensin system (RAS) proteins. We found that RGZ treatment in AoCo group decreases blood pressure values and improves vascular response to acetylcholine, both parameters dependent on PPARγ-stimulation. RGZ lowered serum angiotensin II (AngII) but increased Ang-(1-7) levels. It also decreased 8-hydroxy-2′-deoxyguanosine (8-OH-2dG), malondialdehyde (MDA), and improved the antioxidant capacity. Regarding protein expression of RAS, RGZ decreases ACE and angiotensin II type 1 receptor (AT1R) and improved ACE2, AT2R, and Mas receptor in AoCo rats. Additionally, an in silico analysis revealed that 5′UTR regions of RAS and PPARγ share motifs with a transcriptional regulatory role. We conclude that RGZ lowers blood pressure values by increasing the expression of RAS axis proteins ACE2 and AT2R, decreasing the levels of AngII and increasing levels of Ang-(1-7) in a PPARγ-dependent manner. The in silico analysis is a valuable tool to predict the interaction between PPARγ and RAS. |
| format | Article |
| id | doaj-art-56560442f7104d71aa20feb70e93b59d |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-56560442f7104d71aa20feb70e93b59d2025-02-03T06:07:46ZengWileyPPAR Research1687-47571687-47652019-01-01201910.1155/2019/13717581371758Rosiglitazone, a Ligand to PPARγ, Improves Blood Pressure and Vascular Function through Renin-Angiotensin System RegulationMaría Sánchez-Aguilar0Luz Ibarra-Lara1Leonardo Del Valle-Mondragón2María Esther Rubio-Ruiz3Alicia G. Aguilar-Navarro4Absalom Zamorano-Carrillo5Margarita del Carmen Ramírez-Ortega6Gustavo Pastelín-Hernández7Alicia Sánchez-Mendoza8Department of Pharmacology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 México, Ciudad de México, MexicoDepartment of Pharmacology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 México, Ciudad de México, MexicoDepartment of Pharmacology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 México, Ciudad de México, MexicoDepartment of Physiology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 México, Ciudad de México, MexicoDepartment of Molecular Medicine, Laboratory of Computational Biophysics and Biochemistry, ENMH-IPN, Guillermo Massieu Helguera No. 239, Fracc. La Escalera Ticoman, Gustavo A. Madero, 07320, Ciudad de México, MexicoDepartment of Molecular Medicine, Laboratory of Computational Biophysics and Biochemistry, ENMH-IPN, Guillermo Massieu Helguera No. 239, Fracc. La Escalera Ticoman, Gustavo A. Madero, 07320, Ciudad de México, MexicoDepartment of Pharmacology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 México, Ciudad de México, MexicoDepartment of Pharmacology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 México, Ciudad de México, MexicoDepartment of Pharmacology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 México, Ciudad de México, MexicoRosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPARγ) ligand, has been reported to act as insulin sensitizer and exert cardiovascular actions. In this work, we hypothesized that RGZ exerts a PPARγ–dependent regulation of blood pressure through modulation of angiotensin-converting enzyme (ACE)-type 2 (ACE2)/angiotensin-(1-7)/angiotensin II type-2 receptor (AT2R) axis in an experimental model of high blood pressure. We carried on experiments in normotensive (Sham) and aortic coarctation (AoCo)-induced hypertensive male Wistar rats. Both sham and AoCo rats were treated 7 days with vehicle (V), RGZ (5 mg/kg/day), or RGZ+BADGE (120 mg/kg/day) post-coarctation. We measured blood pressure and vascular reactivity on aortic rings, as well as the expression of renin-angiotensin system (RAS) proteins. We found that RGZ treatment in AoCo group decreases blood pressure values and improves vascular response to acetylcholine, both parameters dependent on PPARγ-stimulation. RGZ lowered serum angiotensin II (AngII) but increased Ang-(1-7) levels. It also decreased 8-hydroxy-2′-deoxyguanosine (8-OH-2dG), malondialdehyde (MDA), and improved the antioxidant capacity. Regarding protein expression of RAS, RGZ decreases ACE and angiotensin II type 1 receptor (AT1R) and improved ACE2, AT2R, and Mas receptor in AoCo rats. Additionally, an in silico analysis revealed that 5′UTR regions of RAS and PPARγ share motifs with a transcriptional regulatory role. We conclude that RGZ lowers blood pressure values by increasing the expression of RAS axis proteins ACE2 and AT2R, decreasing the levels of AngII and increasing levels of Ang-(1-7) in a PPARγ-dependent manner. The in silico analysis is a valuable tool to predict the interaction between PPARγ and RAS.http://dx.doi.org/10.1155/2019/1371758 |
| spellingShingle | María Sánchez-Aguilar Luz Ibarra-Lara Leonardo Del Valle-Mondragón María Esther Rubio-Ruiz Alicia G. Aguilar-Navarro Absalom Zamorano-Carrillo Margarita del Carmen Ramírez-Ortega Gustavo Pastelín-Hernández Alicia Sánchez-Mendoza Rosiglitazone, a Ligand to PPARγ, Improves Blood Pressure and Vascular Function through Renin-Angiotensin System Regulation PPAR Research |
| title | Rosiglitazone, a Ligand to PPARγ, Improves Blood Pressure and Vascular Function through Renin-Angiotensin System Regulation |
| title_full | Rosiglitazone, a Ligand to PPARγ, Improves Blood Pressure and Vascular Function through Renin-Angiotensin System Regulation |
| title_fullStr | Rosiglitazone, a Ligand to PPARγ, Improves Blood Pressure and Vascular Function through Renin-Angiotensin System Regulation |
| title_full_unstemmed | Rosiglitazone, a Ligand to PPARγ, Improves Blood Pressure and Vascular Function through Renin-Angiotensin System Regulation |
| title_short | Rosiglitazone, a Ligand to PPARγ, Improves Blood Pressure and Vascular Function through Renin-Angiotensin System Regulation |
| title_sort | rosiglitazone a ligand to pparγ improves blood pressure and vascular function through renin angiotensin system regulation |
| url | http://dx.doi.org/10.1155/2019/1371758 |
| work_keys_str_mv | AT mariasanchezaguilar rosiglitazonealigandtoppargimprovesbloodpressureandvascularfunctionthroughreninangiotensinsystemregulation AT luzibarralara rosiglitazonealigandtoppargimprovesbloodpressureandvascularfunctionthroughreninangiotensinsystemregulation AT leonardodelvallemondragon rosiglitazonealigandtoppargimprovesbloodpressureandvascularfunctionthroughreninangiotensinsystemregulation AT mariaestherrubioruiz rosiglitazonealigandtoppargimprovesbloodpressureandvascularfunctionthroughreninangiotensinsystemregulation AT aliciagaguilarnavarro rosiglitazonealigandtoppargimprovesbloodpressureandvascularfunctionthroughreninangiotensinsystemregulation AT absalomzamoranocarrillo rosiglitazonealigandtoppargimprovesbloodpressureandvascularfunctionthroughreninangiotensinsystemregulation AT margaritadelcarmenramirezortega rosiglitazonealigandtoppargimprovesbloodpressureandvascularfunctionthroughreninangiotensinsystemregulation AT gustavopastelinhernandez rosiglitazonealigandtoppargimprovesbloodpressureandvascularfunctionthroughreninangiotensinsystemregulation AT aliciasanchezmendoza rosiglitazonealigandtoppargimprovesbloodpressureandvascularfunctionthroughreninangiotensinsystemregulation |