Hydrogen sulfide, oxygen, and calcium regulation in developing human airway smooth muscle.

Preterm infants can develop airway hyperreactivity and impaired bronchodilation following supplemental O ₂ (hyperoxia) in early life, making it important to understand mechanisms of hyperoxia effects. Endogenous hydrogen sulfide (H ₂ S) has anti-inflammatory and vasodilatory effects with oxidative stress. There is little understanding of H ₂ S signaling in developing airways. We hypothesized that the endogenous H ₂ S system is detrimentally influenced by O ₂ and conversely H ₂ S signaling pathways can be leveraged to attenuate deleterious effects of O ₂ . Using human fetal airway smooth muscle (fASM) cells, we investigated baseline expression of endogenous H ₂ S machinery, and effects of exogenous H ₂ S donors NaHS and GYY4137 in the context of moderate hyperoxia, with intracellular calcium regulation as a readout of contractility. Biochemical pathways for endogenous H ₂ S generation and catabolism are present in fASM, and are differentially sensitive to O ₂ toward overall reduction in H ₂ S levels. H ₂ S donors have downstream effects of reducing [Ca ²⁺ ] _i responses to bronchoconstrictor agonist via blunted plasma membrane Ca ²⁺ influx: effects blocked by O ₂ . However, such detrimental O ₂ effects are targetable by exogenous H ₂ S donors such as NaHS and GYY4137. These data provide novel information regarding the potential for H ₂ S to act as a bronchodilator in developing airways in the context of oxygen exposure.
(© 2020 Federation of American Societies for Experimental Biology.)