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Long-Term Chronic Intermittent Hypobaric Hypoxia in Rats Causes an Imbalance in the Asymmetric Dimethylarginine/Nitric Oxide Pathway and ROS Activity: A Possible Synergistic Mechanism for Altitude Pulmonary Hypertension?

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dc.contributor.author Lueneburg, Nicole
dc.contributor.author Siques, Patricia
dc.contributor.author Brito, Julio
dc.contributor.author Arriaza, Karem
dc.contributor.author Pena, Eduardo
dc.contributor.author Klose, Hans
dc.contributor.author León-Velarde, Fabiola
dc.contributor.author Boeger, Rainer H.
dc.date.accessioned 2019-02-22T14:54:33Z
dc.date.available 2019-02-22T14:54:33Z
dc.date.issued 2016
dc.identifier.uri https://hdl.handle.net/20.500.12866/5676
dc.description.abstract Chronic intermittent hypoxia (CIH) and chronic hypoxia (CH) are associated with high-altitude pulmonary hypertension (HAPH). Asymmetric dimethylarginine (ADMA), a NO synthase (NOS) inhibitor, may contribute to HAPH. This study assessed changes in the ADMA/NO pathway and the underlying mechanisms in rat lungs following exposure to CIH or CH simulated in a hypobaric chamber at 428 Torr. Twenty-four adult Wistar rats were randomly assigned to three groups: CIH2x2 (2 days of hypoxia/2 days of normoxia), CH, and NX (permanent normoxia), for 30 days. All analyses were performed in whole lung tissue. L-Arginine and ADMA were analyzed using LC-MS/MS. Under both hypoxic conditions right ventricular hypertrophy was observed (p < 0.01) and endothelial NOS mRNA increased (p < 0.001), but the phosphorylated/nonphosphorylated vasodilator-stimulated phosphoprotein (VASP) ratio was unchanged. ADMA increased (p < 0.001), whereas dimethylarginine dimethylaminohydrolase (DDAH) activity decreased only under CH (p < 0.05). Although arginase activity increased (p < 0.001) and L-arginine exhibited no changes, the L-arginine/ADMA ratio decreased significantly (p < 0.001). Moreover, NOX4 expression increased only under CH (p < 0.01), but malondialdehyde (MDA) increased (up to 2-fold) equally in CIH2x2 and CH (p < 0.001). Our results suggest that ADMA and oxidative stress likely reduce NO bioavailability under altitude hypoxia, which implies greater pulmonary vascular reactivity and tone, despite the more subdued effects observed under CIH. en_US
dc.language.iso eng
dc.publisher Hindawi
dc.relation.ispartofseries Pulmonary Medicine
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Hypobaric Hypoxia en_US
dc.subject Rats en_US
dc.subject Asymmetric Dimethylarginine/Nitric Oxide Pathway en_US
dc.subject ROS Activity en_US
dc.subject Altitude Pulmonary Hypertension en_US
dc.title Long-Term Chronic Intermittent Hypobaric Hypoxia in Rats Causes an Imbalance in the Asymmetric Dimethylarginine/Nitric Oxide Pathway and ROS Activity: A Possible Synergistic Mechanism for Altitude Pulmonary Hypertension? en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1155/2016/6578578
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.07
dc.relation.issn 2090-1844


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