Congenital diaphragmatic hernia: phosphodiesterase-5 and Arginase inhibitors prevent pulmonary vascular hypoplasia in rat lungs

Simple item page
dc.catalogadoraba
dc.contributor.authorToso, Alberto
dc.contributor.authorAranguiz, Óscar
dc.contributor.authorCespedes, Carlos
dc.contributor.authorNavarrete, Orieta
dc.contributor.authorHernández, Cherie
dc.contributor.authorVio, Carlos P.
dc.contributor.authorLuco Illanes, Matías Fernando
dc.contributor.authorCasanello Toledo, Paola Cecilia
dc.contributor.authorKattan Said, Alberto Javier
dc.date.accessioned2024-01-17T19:36:05Z
dc.date.available2024-01-17T19:36:05Z
dc.date.issued2022
dc.description.abstractBackground Severe pulmonary hypoplasia related to congenital diaphragmatic hernia (CDH) continues to be a potentially fatal condition despite advanced postnatal management strategies. Objective To evaluate the effect of the antenatal sildenafil and 2(S)-amino-6-boronohexanoic acid (ABH-Arginase inhibitor) on lung volume, pulmonary vascular development, and nitric oxide (NO) synthesis in a Nitrofen-induced CDH rat model. Methods Nitrofen-induced CDH rat model was used. Nitrofen was administrated on embryonic day(E) 9,5. At E14, five intervention groups were treated separately: Nitrofen, Nitrofen+Sildenafil, Nitrofen+ABH, Nitrofen+Sildenafil+ABH and Control. At term, offspring's lungs were weighed, some paraffin-embedded for histology, others snap-frozen to analyze eNOS, Arginase I-II expression, and activity. Results In CDH-bearing offsprings, ABH or Sildenafil+ABH preserved the total lung/body-weight index (p < 0.001), preventing pulmonary vascular smooth muscle cell hyperproliferation and improving lung morphometry. Sildenafil+ABH increased 1.7-fold the lung nitrite levels (p < 0.01) without changes in eNOS expression. Sildenafil and ABH improved the number of pulmonary vessels. Conclusion These results suggest that in this CDH rat model, the basal activity of Arginase participates in the lung volume and, together with phosphodiesterase-5, regulates NOS activity in the term fetal lung. The combined treatment (Sildenafil+ABH) could revert some of the pulmonary features in CDH by improving the local NO synthesis and preventing smooth muscle cell hyperproliferation. Impact This study presents Arginase inhibition as a new therapeutic target and the importance of the combined antenatal treatment to improve pulmonary vascular development in a congenital diaphragmatic hernia (CDH) rat model. This study shows that the action of an Arginase inhibitor (ABH) enhances the effects already described for sildenafil in this model. These results reinforce the importance of prenatal treatments' synergy in recovering the hypoplastic lung in the Nitrofen-induced CDH rat model.
dc.fechaingreso.objetodigital2024-01-19
dc.format.extent8 páginas
dc.fuente.origenORCID-ene24
dc.identifier.doi10.1038/s41390-022-02366-4
dc.identifier.eissn1530-0447
dc.identifier.issn0031-3998
dc.identifier.scopusidSCOPUS_ID:85142447724
dc.identifier.urihttps://doi.org/10.1038/s41390-022-02366-4
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/80569
dc.identifier.wosidWOS:000886855800001
dc.information.autorucEscuela de Medicina; Luco Illanes, Matías Fernando; 0000-0002-7698-8065; 7023
dc.information.autorucEscuela de Medicina; Casanello Toledo, Paola Cecilia; 0000-0002-2355-1476; 146772
dc.information.autorucEscuela de Medicina; Kattan Said, Alberto Javier; 0000-0002-2911-5982; 53324
dc.information.autorucEscuela de Medicina; Toso, Alberto; 0000-0002-3809-2567; 238020
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final8
dc.pagina.inicio1
dc.revistaPediatric Research
dc.rightsacceso abierto
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleCongenital diaphragmatic hernia: phosphodiesterase-5 and Arginase inhibitors prevent pulmonary vascular hypoplasia in rat lungs
dc.typeartículo
sipa.codpersvinculados7023
sipa.codpersvinculados146772
sipa.codpersvinculados53324
sipa.codpersvinculados238020
sipa.indexWOS
sipa.indexSCOPUS
sipa.trazabilidadORCID;2024-01-08
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
s41390-022-02366-4_Congenital diaphragmatic hernia.pdf
Size:
2.02 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Artículos de revistas