2. Academic Validation
  3. Oxygen-sensitivity and Pulmonary Selectivity of Vasodilators as Potential Drugs for Pulmonary Hypertension

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

  • Antioxidants (Basel). 2021 Jan 21;10(2):155. doi: 10.3390/antiox10020155.
Daniel Morales-Cano 1 2 3 4,  Bianca Barreira 1 2 3,  Beatriz De Olaiz Navarro 5,  María Callejo 1 2 3,  Gema Mondejar-Parreño 1 2 3,  Sergio Esquivel-Ruiz 1 2 3,  Jose A Lorente 3 5,  Laura Moreno 1 2 3,  Joan A Barberá 3 6,  Ángel Cogolludo 1 2 3,  Francisco Perez-Vizcaino 1 2 3
Affiliations

Affiliations

  • 1 Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain.
  • 2 Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28007 Madrid, Spain.
  • 3 Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.
  • 4 Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
  • 5 Hospital Universitario de Getafe, 28905 Madrid, Spain.
  • 6 Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain.
PMID: 33494520 DOI: 10.3390/antiox10020155
Abstract

Current 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.

Keywords

oxygen-sensing; pulmonary hypertension; vascular; vasodilator.

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