Sildenafil Reverses Hypoxic Pulmonary Hypertension in Highland and Lowland Newborn SheepReport as inadecuate




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Resumen

Perinatal exposure to chronic hypoxia induces sustainedhypertension and structural and functional changes in thepulmonary vascular bed. We hypothesized that highland newbornlambs HLNB, 3600 m have a higher pulmonary arterial pressurePAP due in part to a higher activity-expression of phosphodiesterase5 PDE5. We administered sildenafil, a PDE5 inhibitor, duringbasal and hypoxic conditions in the pulmonary hypertensive HLNBand compared them to lowland newborn lambs LLNB, 580 m.Additionally, we compared the vasodilator responses to sildenafil inisolated small pulmonary arteries and the PDE5 mRNA expressionand evaluated the vascular remodeling by histomorphometric analysisin these newborn lambs. Under basal conditions, HLNB had ahigher PAP and cardiac output compared with LLNB. Sildenafildecreased the PAP during basal conditions and completely preventedthe PAP increase during hypoxia in both groups. HLNB showed agreater contractile capacity and a higher maximal dilation to sildenafil.PDE5 mRNA expression did not show significant differencesbetween HLNB and LLNB. The distal pulmonary arteries showed anincreased wall thickness in HLNB. Our results showed that HLNBare more sensitive to sildenafil and therefore could be useful fortreatment of pulmonary hypertension in high-altitude neonates.



Author: Herrera Videla, Emilio; - Ebensperger, Germán; - Krause, Bernardo; - Riquelme González, Raquel; - Reyes, Roberto V.; -

Source: http://repositorio.uchile.cl/



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