Sildenafil reverses hypoxic pulmonary hypertension in highland and lowland newborn sheep

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dc.contributor.authorHerrera, Emilio A.
dc.contributor.authorEbensperger, German
dc.contributor.authorKrause, Bernardo J.
dc.contributor.authorRiquelme, Raquel A.
dc.contributor.authorReyes, Roberto V.
dc.contributor.authorCapetillo, Maria
dc.contributor.authorGonzalez, Sergio
dc.contributor.authorParer, Julian T.
dc.contributor.authorLlanos, Anibal J.
dc.date.accessioned2024-01-10T14:21:39Z
dc.date.available2024-01-10T14:21:39Z
dc.date.issued2008
dc.description.abstractPerinatal exposure to chronic hypoxia induces sustained hypertension and structural and functional changes in the pulmonary vascular bed. We hypothesized that highland newborn lambs (HLNB, 3600 m) have a higher pulmonary arterial pressure (PAP) due in part to a higher activity/expression of phosphodiesterase 5 (PDE5). We administered sildenafil, a PDE5 inhibitor, during basal and hypoxic conditions in the pulmonary hypertensive HLNB and compared them to lowland newborn lambs (LLNB, 580 m). Additionally, we compared the vasodilator responses to sildenafil in isolated small Pulmonary arteries and the PDE5 mRNA expression and evaluated the vascular remodeling by histomorphometric analysis in these newborn lambs. Under basal conditions, HLNB had a higher PAP and cardiac output compared with LLNB. Sildenafil decreased the PAP during basal conditions and completely prevented the PAP increase during hypoxia in both groups. HLNB showed a greater contractile capacity and a higher maximal dilation to sildenafil. PDE5 mRNA expression did not show significant differences between HLNB and LLNB. The distal pulmonary arteries showed an increased wall thickness in HLNB. Our results showed that HLNB are more sensitive to sildenafil and therefore could be useful for treatment of pulmonary hypertension in high-altitude neonates.
dc.description.funderWellcome Trust
dc.fechaingreso.objetodigital2024-05-15
dc.format.extent7 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1203/PDR.0b013e31815ef71c
dc.identifier.issn0031-3998
dc.identifier.pubmedidMEDLINE:18091352
dc.identifier.urihttps://doi.org/10.1203/PDR.0b013e31815ef71c
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79742
dc.identifier.wosidWOS:000252645700012
dc.information.autorucMedicina;González S;S/I;99856
dc.issue.numero2
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final175
dc.pagina.inicio169
dc.publisherINT PEDIATRIC RESEARCH FOUNDATION, INC
dc.revistaPEDIATRIC RESEARCH
dc.rightsacceso restringido
dc.subjectINHALED NITRIC-OXIDE
dc.subjectMECONIUM ASPIRATION SYNDROME
dc.subjectHIGH-ALTITUDE
dc.subjectCYCLIC-GMP
dc.subjectINTRAVENOUS SILDENAFIL
dc.subjectARTERIAL-HYPERTENSION
dc.subjectSMOOTH-MUSCLE
dc.subjectPORCINE MODEL
dc.subjectLUNG
dc.subjectPHOSPHODIESTERASES
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleSildenafil reverses hypoxic pulmonary hypertension in highland and lowland newborn sheep
dc.typeartículo
dc.volumen63
sipa.codpersvinculados99856
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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