Riociguat versus sildenafil on hypoxic pulmonary vasoconstriction and ventilation/perfusion matching

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dc.contributor.authorChamorro, Virginia
dc.contributor.authorMorales Cano, Daniel
dc.contributor.authorMilara, Javier
dc.contributor.authorBarreira, Bianca
dc.contributor.authorMoreno Gutiérrez, Laura
dc.contributor.authorCallejo, Maria
dc.contributor.authorMondejar Parreño, Gema
dc.contributor.authorEsquivel Ruiz, Sergio Antonio
dc.contributor.authorCortijo, Julio
dc.contributor.authorCogolludo Torralba, Ángel Luis
dc.contributor.authorBarberá, Joan A.
dc.contributor.authorPérez Vizcaíno, Francisco
dc.contributor.editorDe Jesús Pérez, Vinicio A.
dc.date.accessioned2024-02-01T08:12:10Z
dc.date.available2024-02-01T08:12:10Z
dc.date.issued2018-01-24
dc.description.abstractIntroduction Current treatment with vasodilators for pulmonary hypertension associated with respiratory diseases is limited by their inhibitory effect on hypoxic pulmonary vasoconstriction (HPV) and uncoupling effects on ventilation-perfusion (V’/Q’). Hypoxia is also a well-known modulator of the nitric oxide (NO) pathway, and may therefore differentially affect the responses to phosphodiesterase 5 (PDE5) inhibitors and soluble guanylyl cyclase (sGC) stimulators. So far, the effects of the sGC stimulator riociguat on HPV have been poorly characterized. Materials and methods Contraction was recorded in pulmonary arteries (PA) in a wire myograph. Anesthetized rats were catheterized to record PA pressure. Ventilation and perfusion were analyzed by micro-CT-SPECT images in rats with pulmonary fibrosis induced by bleomycin. Results The PDE5 inhibitor sildenafil and the sGC stimulator riociguat similarly inhibited HPV in vitro and in vivo. Riociguat was more effective as vasodilator in isolated rat and human PA than sildenafil. Riociguat was ≈3-fold more potent under hypoxic conditions and it markedly inhibited HPV in vivo at a dose that barely affected the thromboxane A2 (TXA2) mimetic U46619-induced pressor responses. Pulmonary fibrosis was associated with V’/Q’ uncoupling and riociguat did not affect the V’/Q’ ratio. Conclusion PDE5 inhibitors and sGC stimulators show a different vasodilator profile. Riociguat was highly effective and potentiated by hypoxia in rat and human PA. In vivo, riociguat preferentially inhibited hypoxic than non-hypoxic vasoconstriction. However, it did not worsen V’/Q’ coupling in a rat model of pulmonary fibrosis.en
dc.description.departmentDepto. de Farmacología y Toxicología
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.statuspub
dc.identifier.citationChamorro V, Morales-Cano D, Milara J, Barreira B, Moreno L, Callejo M, Mondejar-Parreño G, Esquivel-Ruiz S, Cortijo J, Cogolludo Á, Barberá JA, Perez-Vizcaino F. Riociguat versus sildenafil on hypoxic pulmonary vasoconstriction and ventilation/perfusion matching. PLoS One. 2018 Jan 24;13(1):e0191239. doi: 10.1371/journal.pone.0191239
dc.identifier.doi10.1371/journal.pone.0191239
dc.identifier.issn1932-6203
dc.identifier.officialurlhttps//doi.org/10.1371/journal.pone.0191239
dc.identifier.pmid29364918
dc.identifier.relatedurlhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191239
dc.identifier.relatedurlhttps://pubmed.ncbi.nlm.nih.gov/29364918/
dc.identifier.urihttps://hdl.handle.net/20.500.14352/97449
dc.issue.number1
dc.journal.titlePLoS ONE
dc.language.isoeng
dc.publisherPublic Library of Science
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.cdu616.24
dc.subject.keywordMedical hypoxia
dc.subject.keywordOxygen
dc.subject.keywordVasodilators
dc.subject.keywordPulmonary fibrosis
dc.subject.keywordPulmonary arteries
dc.subject.keywordVasoconstriction
dc.subject.keywordArteries
dc.subject.keywordChronic obstructive pulmonary disease
dc.subject.ucmFarmacología (Medicina)
dc.subject.unesco2411.03 Fisiología Cardiovascular
dc.titleRiociguat versus sildenafil on hypoxic pulmonary vasoconstriction and ventilation/perfusion matchingen
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number13
dspace.entity.typePublication
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