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Title: | Riociguat versus sildenafil on hypoxic pulmonary vasoconstriction and ventilation/perfusion matching |
Author: | Chamorro, Virginia Morales-Cano, Daniel Milara, Javier Barreira, Bianca Moreno, Laura Callejo, María Mondejar-Parreño, Gema Esquivel-Ruiz, Sergio Cortijo, Julio Cogolludo, Ángel Barberà i Mir, Joan Albert Perez-Vizcaino, Francisco |
Keywords: | Malalties de l'aparell respiratori Anoxèmia Medicaments Respiratory organs diseases Anoxemia Drugs |
Issue Date: | 24-Jan-2018 |
Publisher: | Public Library of Science (PLoS) |
Abstract: | Introduction 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0191239 |
It is part of: | PLoS One, 2018, vol. 13, num. 1, p. e0191239 |
URI: | http://hdl.handle.net/2445/121779 |
Related resource: | https://doi.org/10.1371/journal.pone.0191239 |
ISSN: | 1932-6203 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Medicina) |
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