RT Journal Article
T1 Role of endogenous hydrogen sulfide in nerve-evoked relaxation of pig terminal bronchioles
A1 Fernandes, Vítor S.
A1 Recio Visedo, María Paz
A1 López-Oliva Muñoz, María Elvira
A1 Martínez Sainz, María Del Pilar
A1 Fernandes Ribeiro, Ana Sofía
A1 Barahona Gomáriz, María Victoria
A1 Martínez Gómez, Ana Cristina
A1 Benedito Castellote, Sara
A1 Agis Torres, Ángel
A1 Cabañero, Alberto
A1 Muñoz, Gemma M.
A1 García Sacristán, Albino
A1 Orensanz Muñoz, Luis Miguel
A1 Hernández Rodríguez, Medardo Vicente
AB Hydrogen sulfide (H2S) is a gasotransmitter employed for intra- and inter-cellular communication in almost all organ systems. This study investigates the role of endogenous H2S in nerve-evoked relaxation of pig terminal bronchioles with 260 μm medium internal lumen diameter. High expression of the H2S synthesis enzyme cystathionine γ-lyase (CSE) in the bronchiolar muscle layer and strong CSE-immunoreactivity within nerve fibers distributed along smooth muscle bundles were observed. Further, endogenous H2S generated in bronchiolar membranes was reduced by CSE inhibition. In contrast, cystathionine β-synthase expression, another H2S synthesis enzyme, however was not consistently detected in the bronchiolar smooth muscle layer. Electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked smooth muscle relaxation. Inhibition of CSE, nitric oxide (NO) synthase, soluble guanylyl cyclase (sGC) and of ATP-dependent K+, transient receptor potential A1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels reduced the EFS relaxation but failed to modify the GYY4137 response. Raising extracellular K+ concentration inhibited the GYY4137 relaxation. Large conductance Ca2+-activated K+ channel blockade reduced both EFS and GYY4137 responses. GYY4137 inhibited the contractions induced by histamine and reduced to a lesser extent the histamine-induced increases in intracellular [Ca2+]. These results suggest that relaxation induced by EFS in the pig terminal bronchioles partly involves the H2S/CSE pathway. H2S response is produced via NO/sGC-independent mechanisms involving K+ channels and intracellular Ca2+ desensitization-dependent pathways. Thus, based on our current results H2S donors might be useful as bronchodilator agents for the treatment of lung diseases with persistent airflow limitation, such as asthma and chronic obstructive lung disease.
PB Elsevier
SN 1094-5539
YR 2016
FD 2016-12-01
LK https://hdl.handle.net/20.500.14352/97722
UL https://hdl.handle.net/20.500.14352/97722
LA eng
NO Fernandes, V. S., Recio, P., López-Oliva, E., Martínez, M. P., Ribeiro, A. S., Barahona, M. V., Martínez, A. C., Benedito, S., Agis-Torres, Á., Cabañero, A., Muñoz, G. M., García-Sacristán, A., Orensanz, L. M., & Hernández, M. (2016). Role of endogenous hydrogen sulfide in nerve-evoked relaxation of pig terminal bronchioles. Pulmonary pharmacology & therapeutics, 41, 1–10. https://doi.org/10.1016/j.pupt.2016.09.003
DS Docta Complutense
RD 2 oct 2024