P2-6 - The Glucagon-Like Peptide-1 Receptor Agonist Inhibits Hypoxia-Induced Pulmonary Hypertension in Mice

Abstract

Introduction: The Glucagon-like peptide-1 receptor (GLP-1R) agonist, liraglutide is an incretin hormone mimetics, a drug for diabetes mellitus. Recently, it is reported that the GLP-1R agonist inhibits endothelial dysfunction, inflammation, and cell proliferation, which are the major molecular findings for pathophysiology of pulmonary arterial hypertension (PAH). However, it is unclear whether the GLP-1R agonist ameliorates PAH. Objective: To investigate the effect of a GLP-1R agonist on the development of PAH. Methods: 8 week-old C57BL6/J mice were injected liraglutide (0.3 mg/kg/day) or saline for total 5 weeks. One week after starting injection, mice were placed in room air or exposed to chronic hypoxia (10% O2) for further 4 weeks. Results: Right ventricular systolic pressure of hypoxia + liraglutide group were significantly reduced compared with that of hypoxia + saline group (30.0 ± 1.5 mmHg vs 34.3 ± 2.2 mmHg, P < .01, n = 7). Right ventricular/body weight ratio of hypoxia + liraglutide group were significantly smaller than that of hypoxia + saline group (P < .01). The expression of eNOS mRNA and the protein expression of phospho-eNOS in the lung was significantly augmented by liraglutide administration under hypoxia (P < .05). Conclusion: The GLP-1R agonist liraglutide reduces right ventricular pressure in hypoxia-induced PAH mice model. This effect is suggested to be through the eNOS activation in pulmonary artery.