Pulmonary hypertension associated with diazoxide: the SUR1 paradox
The ATP-sensitive potassium channels and their regulatory subunits, sulfonylurea receptor 1 (SUR1/Kir6.2) and SUR2/Kir6.1, contribute to the pathophysiology of pulmonary hypertension (PH). Loss-of-function pathogenic variants in the ABCC8 gene, which encodes for SUR1, have been associated with herit...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
European Respiratory Society
2023-11-01
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| Series: | ERJ Open Research |
| Online Access: | http://openres.ersjournals.com/content/9/6/00350-2023.full |
| _version_ | 1797362059447369728 |
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| author | David Montani Fabrice Antigny Etienne-Marie Jutant Marie-Camille Chaumais Hélène Le Ribeuz Julien Grynblat Charles Khouri Marc Humbert |
| author_facet | David Montani Fabrice Antigny Etienne-Marie Jutant Marie-Camille Chaumais Hélène Le Ribeuz Julien Grynblat Charles Khouri Marc Humbert |
| author_sort | David Montani |
| collection | DOAJ |
| description | The ATP-sensitive potassium channels and their regulatory subunits, sulfonylurea receptor 1 (SUR1/Kir6.2) and SUR2/Kir6.1, contribute to the pathophysiology of pulmonary hypertension (PH). Loss-of-function pathogenic variants in the ABCC8 gene, which encodes for SUR1, have been associated with heritable pulmonary arterial hypertension. Conversely, activation of SUR1 and SUR2 leads to the relaxation of pulmonary arteries and reduces cell proliferation and migration. Diazoxide, a SUR1 activator, has been shown to alleviate experimental PH, suggesting its potential as a therapeutic option. However, there are paradoxical reports of diazoxide-induced PH in infants. This review explores the role of SUR1/2 in the pathophysiology of PH and the contradictory effects of diazoxide on the pulmonary vascular bed. Additionally, we conducted a comprehensive literature review of cases of diazoxide-associated PH and analysed data from the World Health Organization pharmacovigilance database (VigiBase). Significant disproportionality signals link diazoxide to PH, while no other SUR activators have been connected with pulmonary vascular disease. Diazoxide-associated PH seems to be dose-dependent and potentially related to acute effects on the pulmonary vascular bed. Further research is required to decipher the differing pulmonary vascular consequences of diazoxide in different age populations and experimental models. |
| first_indexed | 2024-03-08T16:02:09Z |
| format | Article |
| id | doaj.art-0b1daad67e1742e7ae47fb4de467b6e4 |
| institution | Directory Open Access Journal |
| issn | 2312-0541 |
| language | English |
| last_indexed | 2024-03-08T16:02:09Z |
| publishDate | 2023-11-01 |
| publisher | European Respiratory Society |
| record_format | Article |
| series | ERJ Open Research |
| spelling | doaj.art-0b1daad67e1742e7ae47fb4de467b6e42024-01-08T09:57:43ZengEuropean Respiratory SocietyERJ Open Research2312-05412023-11-019610.1183/23120541.00350-202300350-2023Pulmonary hypertension associated with diazoxide: the SUR1 paradoxDavid Montani0Fabrice Antigny1Etienne-Marie Jutant2Marie-Camille Chaumais3Hélène Le Ribeuz4Julien Grynblat5Charles Khouri6Marc Humbert7 Université Paris-Saclay, Faculty of Medicine, Le Kremlin-Bicêtre, France Université Paris-Saclay, Faculty of Medicine, Le Kremlin-Bicêtre, France CHU de Poitiers, Respiratory Department, INSERM CIC 1402, IS-ALIVE Research Group, University of Poitiers, Poitiers, France INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France Université Paris-Saclay, Faculty of Medicine, Le Kremlin-Bicêtre, France Université Paris-Saclay, Faculty of Medicine, Le Kremlin-Bicêtre, France Univ. Grenoble Alpes, HP2 Laboratory, Grenoble, France Université Paris-Saclay, Faculty of Medicine, Le Kremlin-Bicêtre, France The ATP-sensitive potassium channels and their regulatory subunits, sulfonylurea receptor 1 (SUR1/Kir6.2) and SUR2/Kir6.1, contribute to the pathophysiology of pulmonary hypertension (PH). Loss-of-function pathogenic variants in the ABCC8 gene, which encodes for SUR1, have been associated with heritable pulmonary arterial hypertension. Conversely, activation of SUR1 and SUR2 leads to the relaxation of pulmonary arteries and reduces cell proliferation and migration. Diazoxide, a SUR1 activator, has been shown to alleviate experimental PH, suggesting its potential as a therapeutic option. However, there are paradoxical reports of diazoxide-induced PH in infants. This review explores the role of SUR1/2 in the pathophysiology of PH and the contradictory effects of diazoxide on the pulmonary vascular bed. Additionally, we conducted a comprehensive literature review of cases of diazoxide-associated PH and analysed data from the World Health Organization pharmacovigilance database (VigiBase). Significant disproportionality signals link diazoxide to PH, while no other SUR activators have been connected with pulmonary vascular disease. Diazoxide-associated PH seems to be dose-dependent and potentially related to acute effects on the pulmonary vascular bed. Further research is required to decipher the differing pulmonary vascular consequences of diazoxide in different age populations and experimental models.http://openres.ersjournals.com/content/9/6/00350-2023.full |
| spellingShingle | David Montani Fabrice Antigny Etienne-Marie Jutant Marie-Camille Chaumais Hélène Le Ribeuz Julien Grynblat Charles Khouri Marc Humbert Pulmonary hypertension associated with diazoxide: the SUR1 paradox ERJ Open Research |
| title | Pulmonary hypertension associated with diazoxide: the SUR1 paradox |
| title_full | Pulmonary hypertension associated with diazoxide: the SUR1 paradox |
| title_fullStr | Pulmonary hypertension associated with diazoxide: the SUR1 paradox |
| title_full_unstemmed | Pulmonary hypertension associated with diazoxide: the SUR1 paradox |
| title_short | Pulmonary hypertension associated with diazoxide: the SUR1 paradox |
| title_sort | pulmonary hypertension associated with diazoxide the sur1 paradox |
| url | http://openres.ersjournals.com/content/9/6/00350-2023.full |
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