Oxygen-Sensitivity and Pulmonary Selectivity of Vasodilators as Potential Drugs for Pulmonary Hypertension.

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dc.contributor.authorMorales Cano, Daniel
dc.contributor.authorBarreira Barba, Bianca
dc.contributor.authorOlaiz Navarro, Beatriz de
dc.contributor.authorCallejo, María
dc.contributor.authorMondejar Parreño, Gema
dc.contributor.authorEsquivel Ruiz, Sergio Antonio
dc.contributor.authorLorente, Jose A.
dc.contributor.authorMoreno, Laura
dc.contributor.authorBarbera, Joan Albert
dc.contributor.authorCogolludo, Angel
dc.contributor.authorPérez Vizcaíno, Francisco
dc.date.accessioned2023-06-17T08:33:13Z
dc.date.available2023-06-17T08:33:13Z
dc.date.issued2021-01-21
dc.description.abstractCurrent approved therapies for pulmonary hypertension (PH) aim to restore the balance between endothelial mediators in the pulmonary circulation. These drugs may exert vasodilator effects on poorly oxygenated vessels. This may lead to the derivation of blood perfusion towards low ventilated alveoli, i.e., producing ventilation-perfusion mismatch, with detrimental effects on gas exchange. The aim of this study is to analyze the oxygen-sensitivity in vitro of 25 drugs currently used or potentially useful for PH. Additionally, the study analyses the effectiveness of these vasodilators in the pulmonary vs. the systemic vessels. Vasodilator responses were recorded in pulmonary arteries (PA) and mesenteric arteries (MA) from rats and in human PA in a wire myograph under different oxygen concentrations. None of the studied drugs showed oxygen selectivity, being equally or more effective as vasodilators under conditions of low oxygen as compared to high oxygen levels. The drugs studied showed low pulmonary selectivity, being equally or more effective as vasodilators in systemic than in PA. A similar behavior was observed for the members within each drug family. In conclusion, none of the drugs showed optimal vasodilator profile, which may limit their therapeutic efficacy in PH.
dc.description.departmentDepto. de Farmacología y Toxicología
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.sponsorshipEuropean Union
dc.description.sponsorshipMineco
dc.description.sponsorshipInstituto de Salud Carlos III
dc.description.sponsorshipFundación contra la Hipertensión Pulmonar
dc.description.sponsorshipUniversidad Complutense
dc.description.sponsorshipMinisterio de Educación de España
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/78071
dc.identifier.doi10.3390/antiox10020155
dc.identifier.issn2076-3921
dc.identifier.officialurlhttps://www.mdpi.com/journal/antioxidants
dc.identifier.relatedurlhttps://www.mdpi.com/2076-3921/10/2/155
dc.identifier.urihttps://hdl.handle.net/20.500.14352/7426
dc.issue.number2
dc.journal.titleAntioxidants
dc.language.isoeng
dc.page.initial155
dc.publisherMDPI
dc.relation.projectIDFondo Europeo de Desarrollo Regional FEDER
dc.relation.projectIDSAF2011-28150, SAF2016-77222, PID2019- 107363RB-I00
dc.relation.projectIDInstituto de Salud Carlos III (PI15/01100, FIS PI14/01733)
dc.relation.projectIDEmpathy project
dc.relation.projectIDCiberes grant
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.cdu616.131-007.22
dc.subject.cdu615.225.2
dc.subject.keywordPulmonary hypertension
dc.subject.keywordVascular
dc.subject.keywordVasodilator
dc.subject.keywordOxygen-sensing
dc.subject.ucmNeumología
dc.subject.ucmFarmacología (Farmacia)
dc.subject.unesco3205.08 Enfermedades Pulmonares
dc.subject.unesco3209 Farmacología
dc.titleOxygen-Sensitivity and Pulmonary Selectivity of Vasodilators as Potential Drugs for Pulmonary Hypertension.
dc.typejournal article
dc.volume.number10
dspace.entity.typePublication
relation.isAuthorOfPublicationbcd4a75e-c6ee-41db-b675-796b7b7ea5b5
relation.isAuthorOfPublication77765d19-8a6b-490a-954f-bc3d408d1cff
relation.isAuthorOfPublication.latestForDiscoverybcd4a75e-c6ee-41db-b675-796b7b7ea5b5
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