RT Journal Article
T1 Riociguat versus sildenafil on hypoxic pulmonary vasoconstriction and ventilation/perfusion matching
A1 Chamorro, Virginia
A1 Morales Cano, Daniel
A1 Milara, Javier
A1 Barreira, Bianca
A1 Moreno Gutiérrez, Laura
A1 Callejo, Maria
A1 Mondejar Parreño, Gema
A1 Esquivel Ruiz, Sergio Antonio
A1 Cortijo, Julio
A1 Cogolludo Torralba, Ángel Luis
A1 Barberá, Joan A.
A1 Pérez Vizcaíno, Francisco
A2 De Jesús Pérez, Vinicio A.
AB IntroductionCurrent 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 methodsContraction 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.ResultsThe 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.ConclusionPDE5 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.
PB Public Library of Science
SN 1932-6203
YR 2018
FD 2018-01-24
LK https://hdl.handle.net/20.500.14352/97449
UL https://hdl.handle.net/20.500.14352/97449
LA eng
NO 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
DS Docta Complutense
RD 27 sept 2024