Effect of dapagliflozin on pulmonary vascular remodeling in rats with chronic hypoxic pulmonary arterial hypertension

• Published in: Journal of receptors and signal transduction 2024-11, Vol.44 (5-6), p.174-180
• Main Authors: Xu, Yi, Liang, Wenxue, Huo, Juan, Zhang, Ting, Feng, Tianpu, Li, Man, Zhu, Zhemin, Zhou, Ping, Zhu, Shasha, Lu, Yingzhi, Wang, Lei
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; bcl-2-Associated X Protein - metabolism; Benzhydryl Compounds - pharmacology; Disease Models, Animal; Female; Glucosides - pharmacology; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - etiology; Hypertension, Pulmonary - pathology; Hypertrophy, Right Ventricular - drug therapy; Hypertrophy, Right Ventricular - pathology; Hypertrophy, Right Ventricular - physiopathology; Hypoxia - drug therapy; Lung - drug effects; Lung - metabolism; Lung - pathology; Proto-Oncogene Proteins c-bcl-2 - metabolism; Pulmonary Arterial Hypertension - drug therapy; Pulmonary Arterial Hypertension - etiology; Pulmonary Arterial Hypertension - metabolism; Pulmonary Arterial Hypertension - pathology; Pulmonary Artery - drug effects; Pulmonary Artery - metabolism; Pulmonary Artery - pathology; Rats; Rats, Sprague-Dawley; Sodium-Glucose Transporter 2 Inhibitors - pharmacology; Vascular Remodeling - drug effects
• ISSN: 1079-9893; 1532-4281; 1532-4281
• DOI: 10.1080/10799893.2024.2433083

To investigate the effects of sodium-glucose co-transporter 2 inhibitor dapagliflozin on pulmonary vascular remodeling in a rat model of chronic hypoxic pulmonary arterial hypertension. Eighteen female Sprague-Dawley rats were divided into three groups: control (CON), chronic hypoxia (HYP), and chronic hypoxia + dapagliflozin. The HYP and dapagliflozin groups were subjected to hypoxia and received saline or dapagliflozin. The CON group was normoxic and received saline. Body weight and fasting blood glucose were measured, and after 21 days, lung and heart tissues were analyzed for pulmonary artery reconstruction and right ventricular hypertrophy. Western blotting assessed Bax and Bcl-2 protein levels. Chronic hypoxia increased pulmonary artery wall thickness and lung fibrosis and caused right ventricular hypertrophy. Dapagliflozin reduced these changes, decreasing artery wall thickness, fibrosis, and hypertrophy while increasing the Bax/Bcl-2 ratio. Dapagliflozin alleviates chronic hypoxia-induced pulmonary artery wall thickening and lung tissue fibrosis in rats, potentially through proapoptotic effects.