Vitamin D as an add-on therapy to phosphodiesterase-5 inhibitor in experimental pulmonary arterial hypertension

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Adão, Rui
  • dc.contributor.author Barreira, Bianca
  • dc.contributor.author Paternoster, Elena
  • dc.contributor.author Morales-Cano, Daniel
  • dc.contributor.author Olivencia, Miguel A.
  • dc.contributor.author Quintana-Villamandos, Begoña
  • dc.contributor.author Rodríguez Chiaradia, Diego Agustín
  • dc.contributor.author Cogolludo, Angel
  • dc.contributor.author Perez-Vizcaino, Francisco
  • dc.date.accessioned 2025-10-03T06:21:54Z
  • dc.date.available 2025-10-03T06:21:54Z
  • dc.date.issued 2025
  • dc.description.abstract Severe vitamin D (vitD) deficiency is a very common condition in patients with pulmonary arterial hypertension (PAH), and it is a predictor of poor prognosis. There is emerging evidence suggesting a connection between the insufficient response to phosphodiesterase-5 inhibitors (PDE5i) and vitD deficiency in patients with PAH. In the present translational study, vitD deficiency was induced in Wistar rats by exposure to vitD-free diet for 5 wk and followed by Su5416 administration and hypoxia (10%) for 3 wk, a standard experimental model of PAH. Then, rats were randomized to either 1) the PDE5i tadalafil and continuing vitD-free diet or 2) tadalafil plus a single dose of vitD and standard diet for 4 wk. VitD supplementation improved exercise capacity and right ventricular function and decreased systolic right ventricular pressure, right atrial hypertrophy, right ventricular hypertrophy, and pulmonary arterial remodeling. VitD improved the ex vivo endothelium-dependent response to acetylcholine, indicating an improvement in NO bioavailability, which also resulted in an acute ex vivo response to sildenafil. Thus, the restoration of vitD, by rescuing endothelial function and PDE5i effectiveness, significantly improved the histological, hemodynamic, and functional features of rats with PAH. VitD may be especially beneficial for PDE5i-treated patients with PAH. NEW & NOTEWORTHY Severe vitamin D deficiency is very prevalent in patients with pulmonary arterial hypertension. We show that addition of vitamin D to the standard PDE5 inhibitor tadalafil increases its therapeutic efficacy in pulmonary hypertensive rats that were deficient in vitamin D.
  • dc.description.sponsorship This study was supported by grants from Ministerio de Economía y Competitividad (PID2019-107363RB-I00 and PID2020-117939RB-I00), Fundación Contra la Hipertensión Pulmonar (FCHP, Empathy study) and Sociedad Española de Neumología y Cirugía Torácica (SEPAR, 1204/2022). R.A. is funded by the EC Horizon 2020 Marie Skłodowska-Curie grant (No. 847635), and acknowledges Fundação para a Ciência e a Technologia (FCT) under the auspices of the project RELAX-2-PAH (2022.08921.PTDC; https://doi.org/10.54499/2022.08921.PTDC). M.A.O. is funded by Universidad Complutense/Banco Santander CT63/19-CT64/19.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Adão R, Barreira B, Paternoster E, Morales-Cano D, Olivencia MA, Quintana-Villamandos B, et al. Vitamin D as an add-on therapy to phosphodiesterase-5 inhibitor in experimental pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. 2025 Feb 1;328(2):L253-9. DOI: 10.1152/ajplung.00319.2024
  • dc.identifier.doi http://dx.doi.org/10.1152/ajplung.00319.2024
  • dc.identifier.issn 1040-0605
  • dc.identifier.uri http://hdl.handle.net/10230/71356
  • dc.language.iso eng
  • dc.publisher American Physiological Society
  • dc.relation.ispartof Am J Physiol Lung Cell Mol Physiol. 2025 Feb 1;328(2):L253-9
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/847635
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-107363RB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-117939RB-I00
  • dc.rights Copyright © 2025 The Authors. Licensed under Creative Commons Attribution CC-BY 4.0 (http://creativecommons.org/licenses/by/4.0/). Published by the American Physiological Society.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Phosphodiesterase-5 inhibitor
  • dc.subject.keyword Pulmonary hypertension
  • dc.subject.keyword Tadalafil
  • dc.subject.keyword Vitamin D
  • dc.title Vitamin D as an add-on therapy to phosphodiesterase-5 inhibitor in experimental pulmonary arterial hypertension
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Hospital del Mar Research Institute)
Articles (Departament de Medicina i Ciències de la Vida)
Documents OpenAIRE (Open Access Infrastructure for Research in Europe)