β3-adrenoceptor agonism exerts lung protection in a rat model of bronchopulmonary dysplasia

Year: 2026

Authors: Pini A., Nardini P., Zizi V., Molino M., Calvani M., Carrozzo F., Amato R., Guasti D., Biagini D., Di Francesco F., Silvestri L., Franceschini A., Bani D., Imbimbo E., Filippi L.

Autors Affiliation: Univ Florence, Dept Expt & Clin Med, Florence 50139, Italy; Meyer Childrens Hosp IRCCS, Unit Translat & Precis Med, Florence, Italy; Univ Pisa, Dept Chem & Ind Chem, Pisa, Italy; Natl Inst Opt CNR INO, Natl Res Council, Sesto Fiorentino, Italy; Univ Pisa, Dept Clin & Expt Med, Neonatol & Neonatal Intens Care Unit, Pisa 56124, Italy.

Abstract: Background and Purpose Bronchopulmonary dysplasia (BPD) affects premature newborns, particularly those receiving supplemental oxygen therapy. Exposure of underdeveloped lungs to oxygen levels higher than the intrauterine environment causes oxidative stress, impairing alveolarisation, vascularisation and causing fibrosis. The beta 3-adrenoceptor could represent a promising target for BPD treatment because of its oxygen-dependent regulation, ability to reduce oxidative stress and protection against intestinal hyperoxia-induced damage.Experimental Approach In this study, neonatal rat pups were reared under hyperoxia for 2 weeks to induce a BPD-like disease and treated with the beta 3-adrenoceptor agonist BRL37344 (1, 3 or 6 mg kg-1).Key Results Through oxidative stress, hyperoxia decreases pulmonary volume, impairs alveolarisation and vascularisation, and causes fibrosis and type II pneumocyte hyperplasia, thereby reducing survival rates. BRL37344 at 3 mg kg-1 counteracted these alterations, doubling survival rates.Conclusions and Implications Our findings demonstrate a new role for beta 3-adrenoceptors in protecting the lungs from hyperoxic injury, suggesting its pharmacological activation as a strategy for treating Bronchopulmonary dysplasia of prematurity and, possibly, other lung fibrosis-related disorders.

Journal/Review: BRITISH JOURNAL OF PHARMACOLOGY

More Information: This study was co-funded by the Italian Ministry of University and Research (PRIN 2022 D.D. 104, 02/02/2022) through the European Union, NextGenerationEU (OBERON, 2022FYBMEX, Italy); the Meyer Foundation (Meyer Children’s University Hospital, Florence, Italy, n. 0106182); and Intesa San Paolo, Turin, Italy (n. B/202 2/0198).
KeyWords: beta 3-adrenoceptor; bronchopulmonary dysplasia; lung; oxidative stress; PDGRF; prematurity
DOI: 10.1111/bph.70333