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Restoration of Vitamin D Levels Improves Endothelial Function and Increases TASK-Like K(+) Currents in Pulmonary Arterial Hypertension Associated with Vitamin D Deficiency

Background: Vitamin D (vitD) deficiency is highly prevalent in patients with pulmonary arterial hypertension (PAH). Moreover, PAH-patients with lower levels of vitD have worse prognosis. We hypothesize that recovering optimal levels of vitD in an animal model of PAH previously depleted of vitD impro...

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Autores principales: Callejo, Maria, Morales-Cano, Daniel, Mondejar-Parreño, Gema, Barreira, Bianca, Esquivel-Ruiz, Sergio, Olivencia, Miguel Angel, Moreno, Laura, Cogolludo, Angel, Perez-Vizcaino, Francisco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227733/
https://www.ncbi.nlm.nih.gov/pubmed/34073580
http://dx.doi.org/10.3390/biom11060795
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author Callejo, Maria
Morales-Cano, Daniel
Mondejar-Parreño, Gema
Barreira, Bianca
Esquivel-Ruiz, Sergio
Olivencia, Miguel Angel
Moreno, Laura
Cogolludo, Angel
Perez-Vizcaino, Francisco
author_facet Callejo, Maria
Morales-Cano, Daniel
Mondejar-Parreño, Gema
Barreira, Bianca
Esquivel-Ruiz, Sergio
Olivencia, Miguel Angel
Moreno, Laura
Cogolludo, Angel
Perez-Vizcaino, Francisco
author_sort Callejo, Maria
collection PubMed
description Background: Vitamin D (vitD) deficiency is highly prevalent in patients with pulmonary arterial hypertension (PAH). Moreover, PAH-patients with lower levels of vitD have worse prognosis. We hypothesize that recovering optimal levels of vitD in an animal model of PAH previously depleted of vitD improves the hemodynamics, the endothelial dysfunction and the ionic remodeling. Methods: Male Wistar rats were fed a vitD-free diet for five weeks and then received a single dose of Su5416 (20 mg/Kg) and were exposed to vitD-free diet and chronic hypoxia (10% O(2)) for three weeks to induce PAH. Following this, vitD deficient rats with PAH were housed in room air and randomly divided into two groups: (a) continued on vitD-free diet or (b) received an oral dose of 100,000 IU/Kg of vitD plus standard diet for three weeks. Hemodynamics, pulmonary vascular remodeling, pulmonary arterial contractility, and K(+) currents were analyzed. Results: Recovering optimal levels of vitD improved endothelial function, measured by an increase in the endothelium-dependent vasodilator response to acetylcholine. It also increased the activity of TASK-1 potassium channels. However, vitD supplementation did not reduce pulmonary pressure and did not ameliorate pulmonary vascular remodeling and right ventricle hypertrophy. Conclusions: Altogether, these data suggest that in animals with PAH and severe deficit of vitD, restoring vitD levels to an optimal range partially improves some pathophysiological features of PAH.
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spelling pubmed-82277332021-06-26 Restoration of Vitamin D Levels Improves Endothelial Function and Increases TASK-Like K(+) Currents in Pulmonary Arterial Hypertension Associated with Vitamin D Deficiency Callejo, Maria Morales-Cano, Daniel Mondejar-Parreño, Gema Barreira, Bianca Esquivel-Ruiz, Sergio Olivencia, Miguel Angel Moreno, Laura Cogolludo, Angel Perez-Vizcaino, Francisco Biomolecules Article Background: Vitamin D (vitD) deficiency is highly prevalent in patients with pulmonary arterial hypertension (PAH). Moreover, PAH-patients with lower levels of vitD have worse prognosis. We hypothesize that recovering optimal levels of vitD in an animal model of PAH previously depleted of vitD improves the hemodynamics, the endothelial dysfunction and the ionic remodeling. Methods: Male Wistar rats were fed a vitD-free diet for five weeks and then received a single dose of Su5416 (20 mg/Kg) and were exposed to vitD-free diet and chronic hypoxia (10% O(2)) for three weeks to induce PAH. Following this, vitD deficient rats with PAH were housed in room air and randomly divided into two groups: (a) continued on vitD-free diet or (b) received an oral dose of 100,000 IU/Kg of vitD plus standard diet for three weeks. Hemodynamics, pulmonary vascular remodeling, pulmonary arterial contractility, and K(+) currents were analyzed. Results: Recovering optimal levels of vitD improved endothelial function, measured by an increase in the endothelium-dependent vasodilator response to acetylcholine. It also increased the activity of TASK-1 potassium channels. However, vitD supplementation did not reduce pulmonary pressure and did not ameliorate pulmonary vascular remodeling and right ventricle hypertrophy. Conclusions: Altogether, these data suggest that in animals with PAH and severe deficit of vitD, restoring vitD levels to an optimal range partially improves some pathophysiological features of PAH. MDPI 2021-05-26 /pmc/articles/PMC8227733/ /pubmed/34073580 http://dx.doi.org/10.3390/biom11060795 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Callejo, Maria
Morales-Cano, Daniel
Mondejar-Parreño, Gema
Barreira, Bianca
Esquivel-Ruiz, Sergio
Olivencia, Miguel Angel
Moreno, Laura
Cogolludo, Angel
Perez-Vizcaino, Francisco
Restoration of Vitamin D Levels Improves Endothelial Function and Increases TASK-Like K(+) Currents in Pulmonary Arterial Hypertension Associated with Vitamin D Deficiency
title Restoration of Vitamin D Levels Improves Endothelial Function and Increases TASK-Like K(+) Currents in Pulmonary Arterial Hypertension Associated with Vitamin D Deficiency
title_full Restoration of Vitamin D Levels Improves Endothelial Function and Increases TASK-Like K(+) Currents in Pulmonary Arterial Hypertension Associated with Vitamin D Deficiency
title_fullStr Restoration of Vitamin D Levels Improves Endothelial Function and Increases TASK-Like K(+) Currents in Pulmonary Arterial Hypertension Associated with Vitamin D Deficiency
title_full_unstemmed Restoration of Vitamin D Levels Improves Endothelial Function and Increases TASK-Like K(+) Currents in Pulmonary Arterial Hypertension Associated with Vitamin D Deficiency
title_short Restoration of Vitamin D Levels Improves Endothelial Function and Increases TASK-Like K(+) Currents in Pulmonary Arterial Hypertension Associated with Vitamin D Deficiency
title_sort restoration of vitamin d levels improves endothelial function and increases task-like k(+) currents in pulmonary arterial hypertension associated with vitamin d deficiency
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227733/
https://www.ncbi.nlm.nih.gov/pubmed/34073580
http://dx.doi.org/10.3390/biom11060795
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