2026-06-27T15:23:13Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/974492024-10-11T16:58:04Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Chamorro, Virginia author Morales Cano, Daniel author Milara, Javier author Barreira, Bianca author Moreno Gutiérrez, Laura author Callejo Arranz, María author Mondejar Parreño, Gema author Esquivel Ruiz, Sergio Antonio author Cortijo, Julio author Cogolludo Torralba, Ángel Luis author Barberá, Joan A. author Pérez Vizcaíno, Francisco editor De Jesús Pérez, Vinicio A. 2024-02-01T08:12:10Z 2024-02-01T08:12:10Z 2018-01-24 Chamorro 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 1932-6203 10.1371/journal.pone.0191239 https://hdl.handle.net/20.500.14352/97449 https//doi.org/10.1371/journal.pone.0191239 29364918 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191239https://pubmed.ncbi.nlm.nih.gov/29364918/ 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. eng Attribution 4.0 International Riociguat versus sildenafil on hypoxic pulmonary vasoconstriction and ventilation/perfusion matching journal article 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URL https://docta.ucm.es/bitstreams/9dae49d9-06d9-465f-a778-b70f032f96f8/download File MD5 93d17cd198da963f9fd74e18ffd076c9 2940642 application/pdf Chamorro and Morales et al_PlosOne.pdf