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Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension
Bronchopulmonary dysplasia (BPD), a common complication of preterm birth, is associated with pulmonary hypertension (PH) in 25% of infants with moderate to severe BPD. Neonatal mice exposed to hyperoxia for 14d develop lung disease similar to BPD, with evidence of associated PH. The cyclic guanosine...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549891/ https://www.ncbi.nlm.nih.gov/pubmed/28792962 http://dx.doi.org/10.1371/journal.pone.0180957 |
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author | Perez, Marta Lee, Keng Jin Cardona, Herminio J. Taylor, Joann M. Robbins, Mary E. Waypa, Gregory B. Berkelhamer, Sara K. Farrow, Kathryn N. |
author_facet | Perez, Marta Lee, Keng Jin Cardona, Herminio J. Taylor, Joann M. Robbins, Mary E. Waypa, Gregory B. Berkelhamer, Sara K. Farrow, Kathryn N. |
author_sort | Perez, Marta |
collection | PubMed |
description | Bronchopulmonary dysplasia (BPD), a common complication of preterm birth, is associated with pulmonary hypertension (PH) in 25% of infants with moderate to severe BPD. Neonatal mice exposed to hyperoxia for 14d develop lung disease similar to BPD, with evidence of associated PH. The cyclic guanosine monophosphate (cGMP) signaling pathway has not been well studied in BPD-associated PH. In addition, there is little data about the natural history of hyperoxia-induced PH in mice or the utility of phosphodiesterase-5 (PDE5) inhibition in established disease. C57BL/6 mice were placed in room air or 75% O(2) within 24h of birth for 14d, followed by recovery in room air for an additional 7 days (21d). Additional pups were treated with either vehicle or sildenafil for 7d during room air recovery. Mean alveolar area, pulmonary artery (PA) medial wall thickness (MWT), RVH, and vessel density were evaluated at 21d. PA protein from 21d animals was analyzed for soluble guanylate cyclase (sGC) activity, PDE5 activity, and cGMP levels. Neonatal hyperoxia exposure results in persistent alveolar simplification, RVH, decreased vessel density, increased MWT, and disrupted cGMP signaling despite a period of room air recovery. Delayed treatment with sildenafil during room air recovery is associated with improved RVH and decreased PA PDE5 activity, but does not have significant effects on alveolar simplification, PA remodeling, or vessel density. These data are consistent with clinical studies suggesting inconsistent effects of sildenafil treatment in infants with BPD-associated PH. |
format | Online Article Text |
id | pubmed-5549891 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55498912017-08-15 Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension Perez, Marta Lee, Keng Jin Cardona, Herminio J. Taylor, Joann M. Robbins, Mary E. Waypa, Gregory B. Berkelhamer, Sara K. Farrow, Kathryn N. PLoS One Research Article Bronchopulmonary dysplasia (BPD), a common complication of preterm birth, is associated with pulmonary hypertension (PH) in 25% of infants with moderate to severe BPD. Neonatal mice exposed to hyperoxia for 14d develop lung disease similar to BPD, with evidence of associated PH. The cyclic guanosine monophosphate (cGMP) signaling pathway has not been well studied in BPD-associated PH. In addition, there is little data about the natural history of hyperoxia-induced PH in mice or the utility of phosphodiesterase-5 (PDE5) inhibition in established disease. C57BL/6 mice were placed in room air or 75% O(2) within 24h of birth for 14d, followed by recovery in room air for an additional 7 days (21d). Additional pups were treated with either vehicle or sildenafil for 7d during room air recovery. Mean alveolar area, pulmonary artery (PA) medial wall thickness (MWT), RVH, and vessel density were evaluated at 21d. PA protein from 21d animals was analyzed for soluble guanylate cyclase (sGC) activity, PDE5 activity, and cGMP levels. Neonatal hyperoxia exposure results in persistent alveolar simplification, RVH, decreased vessel density, increased MWT, and disrupted cGMP signaling despite a period of room air recovery. Delayed treatment with sildenafil during room air recovery is associated with improved RVH and decreased PA PDE5 activity, but does not have significant effects on alveolar simplification, PA remodeling, or vessel density. These data are consistent with clinical studies suggesting inconsistent effects of sildenafil treatment in infants with BPD-associated PH. Public Library of Science 2017-08-09 /pmc/articles/PMC5549891/ /pubmed/28792962 http://dx.doi.org/10.1371/journal.pone.0180957 Text en © 2017 Perez et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Perez, Marta Lee, Keng Jin Cardona, Herminio J. Taylor, Joann M. Robbins, Mary E. Waypa, Gregory B. Berkelhamer, Sara K. Farrow, Kathryn N. Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension |
title | Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension |
title_full | Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension |
title_fullStr | Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension |
title_full_unstemmed | Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension |
title_short | Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension |
title_sort | aberrant cgmp signaling persists during recovery in mice with oxygen-induced pulmonary hypertension |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549891/ https://www.ncbi.nlm.nih.gov/pubmed/28792962 http://dx.doi.org/10.1371/journal.pone.0180957 |
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