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The Action of 2-Aminoethyldiphenyl Borinate on the Pulmonary Arterial Hypertension and Remodeling of High-Altitude Hypoxemic Lambs
Calcium signaling is key for the contraction, differentiation, and proliferation of pulmonary arterial smooth muscle cells. Furthermore, calcium influx through store-operated channels (SOCs) is particularly important in the vasoconstrictor response to hypoxia. Previously, we found a decrease in pulm...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784838/ https://www.ncbi.nlm.nih.gov/pubmed/35082688 http://dx.doi.org/10.3389/fphys.2021.765281 |
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author | Castillo-Galán, Sebastián Parrau, Daniela Hernández, Ismael Quezada, Sebastián Díaz, Marcela Ebensperger, Germán Herrera, Emilio A. Moraga, Fernando A. Iturriaga, Rodrigo Llanos, Aníbal J. Reyes, Roberto V. |
author_facet | Castillo-Galán, Sebastián Parrau, Daniela Hernández, Ismael Quezada, Sebastián Díaz, Marcela Ebensperger, Germán Herrera, Emilio A. Moraga, Fernando A. Iturriaga, Rodrigo Llanos, Aníbal J. Reyes, Roberto V. |
author_sort | Castillo-Galán, Sebastián |
collection | PubMed |
description | Calcium signaling is key for the contraction, differentiation, and proliferation of pulmonary arterial smooth muscle cells. Furthermore, calcium influx through store-operated channels (SOCs) is particularly important in the vasoconstrictor response to hypoxia. Previously, we found a decrease in pulmonary hypertension and remodeling in normoxic newborn lambs partially gestated under chronic hypoxia, when treated with 2-aminoethyldiphenyl borinate (2-APB), a non-specific SOC blocker. However, the effects of 2-APB are unknown in neonates completely gestated, born, and raised under environmental hypoxia. Accordingly, we studied the effects of 2-APB-treatment on the cardiopulmonary variables in lambs under chronic hypobaric hypoxia. Experiments were done in nine newborn lambs gestated, born, and raised in high altitude (3,600 m): five animals were treated with 2-APB [intravenous (i.v.) 10 mg kg(–1)] for 10 days, while other four animals received vehicle. During the treatment, cardiopulmonary variables were measured daily, and these were also evaluated during an acute episode of superimposed hypoxia, 1 day after the end of the treatment. Furthermore, pulmonary vascular remodeling was assessed by histological analysis 2 days after the end of the treatment. Basal cardiac output and mean systemic arterial pressure (SAP) and resistance from 2-APB- and vehicle-treated lambs did not differ along with the treatment. Mean pulmonary arterial pressure (mPAP) decreased after the first day of 2-APB treatment and remained lower than the vehicle-treated group until the third day, and during the fifth, sixth, and ninth day of treatment. The net mPAP increase in response to acute hypoxia did not change, but the pressure area under the curve (AUC) during hypoxia was slightly lower in 2-APB-treated lambs than in vehicle-treated lambs. Moreover, the 2-APB treatment decreased the pulmonary arterial wall thickness and the α-actin immunoreactivity and increased the luminal area with no changes in the vascular density. Our findings show that 2-APB treatment partially reduced the contractile hypoxic response and reverted the pulmonary vascular remodeling, but this is not enough to normalize the pulmonary hemodynamics in chronically hypoxic newborn lambs. |
format | Online Article Text |
id | pubmed-8784838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87848382022-01-25 The Action of 2-Aminoethyldiphenyl Borinate on the Pulmonary Arterial Hypertension and Remodeling of High-Altitude Hypoxemic Lambs Castillo-Galán, Sebastián Parrau, Daniela Hernández, Ismael Quezada, Sebastián Díaz, Marcela Ebensperger, Germán Herrera, Emilio A. Moraga, Fernando A. Iturriaga, Rodrigo Llanos, Aníbal J. Reyes, Roberto V. Front Physiol Physiology Calcium signaling is key for the contraction, differentiation, and proliferation of pulmonary arterial smooth muscle cells. Furthermore, calcium influx through store-operated channels (SOCs) is particularly important in the vasoconstrictor response to hypoxia. Previously, we found a decrease in pulmonary hypertension and remodeling in normoxic newborn lambs partially gestated under chronic hypoxia, when treated with 2-aminoethyldiphenyl borinate (2-APB), a non-specific SOC blocker. However, the effects of 2-APB are unknown in neonates completely gestated, born, and raised under environmental hypoxia. Accordingly, we studied the effects of 2-APB-treatment on the cardiopulmonary variables in lambs under chronic hypobaric hypoxia. Experiments were done in nine newborn lambs gestated, born, and raised in high altitude (3,600 m): five animals were treated with 2-APB [intravenous (i.v.) 10 mg kg(–1)] for 10 days, while other four animals received vehicle. During the treatment, cardiopulmonary variables were measured daily, and these were also evaluated during an acute episode of superimposed hypoxia, 1 day after the end of the treatment. Furthermore, pulmonary vascular remodeling was assessed by histological analysis 2 days after the end of the treatment. Basal cardiac output and mean systemic arterial pressure (SAP) and resistance from 2-APB- and vehicle-treated lambs did not differ along with the treatment. Mean pulmonary arterial pressure (mPAP) decreased after the first day of 2-APB treatment and remained lower than the vehicle-treated group until the third day, and during the fifth, sixth, and ninth day of treatment. The net mPAP increase in response to acute hypoxia did not change, but the pressure area under the curve (AUC) during hypoxia was slightly lower in 2-APB-treated lambs than in vehicle-treated lambs. Moreover, the 2-APB treatment decreased the pulmonary arterial wall thickness and the α-actin immunoreactivity and increased the luminal area with no changes in the vascular density. Our findings show that 2-APB treatment partially reduced the contractile hypoxic response and reverted the pulmonary vascular remodeling, but this is not enough to normalize the pulmonary hemodynamics in chronically hypoxic newborn lambs. Frontiers Media S.A. 2022-01-10 /pmc/articles/PMC8784838/ /pubmed/35082688 http://dx.doi.org/10.3389/fphys.2021.765281 Text en Copyright © 2022 Castillo-Galán, Parrau, Hernández, Quezada, Díaz, Ebensperger, Herrera, Moraga, Iturriaga, Llanos and Reyes. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Castillo-Galán, Sebastián Parrau, Daniela Hernández, Ismael Quezada, Sebastián Díaz, Marcela Ebensperger, Germán Herrera, Emilio A. Moraga, Fernando A. Iturriaga, Rodrigo Llanos, Aníbal J. Reyes, Roberto V. The Action of 2-Aminoethyldiphenyl Borinate on the Pulmonary Arterial Hypertension and Remodeling of High-Altitude Hypoxemic Lambs |
title | The Action of 2-Aminoethyldiphenyl Borinate on the Pulmonary Arterial Hypertension and Remodeling of High-Altitude Hypoxemic Lambs |
title_full | The Action of 2-Aminoethyldiphenyl Borinate on the Pulmonary Arterial Hypertension and Remodeling of High-Altitude Hypoxemic Lambs |
title_fullStr | The Action of 2-Aminoethyldiphenyl Borinate on the Pulmonary Arterial Hypertension and Remodeling of High-Altitude Hypoxemic Lambs |
title_full_unstemmed | The Action of 2-Aminoethyldiphenyl Borinate on the Pulmonary Arterial Hypertension and Remodeling of High-Altitude Hypoxemic Lambs |
title_short | The Action of 2-Aminoethyldiphenyl Borinate on the Pulmonary Arterial Hypertension and Remodeling of High-Altitude Hypoxemic Lambs |
title_sort | action of 2-aminoethyldiphenyl borinate on the pulmonary arterial hypertension and remodeling of high-altitude hypoxemic lambs |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784838/ https://www.ncbi.nlm.nih.gov/pubmed/35082688 http://dx.doi.org/10.3389/fphys.2021.765281 |
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