| アブストラクト | 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. |
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| 投稿者 | Montani, David; Antigny, Fabrice; Jutant, Etienne-Marie; Chaumais, Marie-Camille; Le Ribeuz, Helene; Grynblat, Julien; Khouri, Charles; Humbert, Marc |
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| 組織名 | Universite Paris-Saclay, Faculty of Medicine, Le Kremlin-Bicetre, France.;INSERM UMR_S 999, Hopital Marie Lannelongue, Le Plessis Robinson, France.;Assistance Publique-Hopitaux de Paris (AP-HP), Department of Respiratory and;Intensive Care Medicine, Pulmonary Hypertension National Referral Centre, Hopital;Bicetre, DMU 5 Thorinno, Le Kremlin-Bicetre, France.;CHU de Poitiers, Respiratory Department, INSERM CIC 1402, IS-ALIVE Research;Group, University of Poitiers, Poitiers, France.;Assistance Publique-Hopitaux de Paris (AP-HP), Department of Pharmacy, Hopital;Bicetre, Le Kremlin-Bicetre, France.;Universite Paris-Saclay, Faculty of Pharmacy, Saclay, France.;Univ. Grenoble Alpes, HP2 Laboratory, Grenoble, France.;Grenoble Alpes University Hospital, Pharmacovigilance Unit, Grenoble, France. |
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