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Melatonin Attenuates Pulmonary Hypertension in Chronically Hypoxic Rats

Chronic hypoxia induces pulmonary hypertension and vascular remodeling, which are clinically relevant to patients with chronic obstructive pulmonary disease (COPD) associated with a decreased level of nitric oxide (NO). Oxidative stress and inflammation play important roles in the pathophysiological...

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Autores principales: Hung, Ming Wai, Yeung, Hang Mee, Lau, Chi Fai, Poon, Angela Ming See, Tipoe, George L., Fung, Man Lung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485949/
https://www.ncbi.nlm.nih.gov/pubmed/28538666
http://dx.doi.org/10.3390/ijms18061125
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author Hung, Ming Wai
Yeung, Hang Mee
Lau, Chi Fai
Poon, Angela Ming See
Tipoe, George L.
Fung, Man Lung
author_facet Hung, Ming Wai
Yeung, Hang Mee
Lau, Chi Fai
Poon, Angela Ming See
Tipoe, George L.
Fung, Man Lung
author_sort Hung, Ming Wai
collection PubMed
description Chronic hypoxia induces pulmonary hypertension and vascular remodeling, which are clinically relevant to patients with chronic obstructive pulmonary disease (COPD) associated with a decreased level of nitric oxide (NO). Oxidative stress and inflammation play important roles in the pathophysiological processes in COPD. We examined the hypothesis that daily administration of melatonin (10 mg/kg) mitigates the pulmonary hypertension and vascular remodeling in chronically hypoxic rats. The right ventricular systolic pressure (RVSP) and the thickness of pulmonary arteriolar wall were measured from normoxic control, vehicle- and melatonin-treated hypoxic rats exposed to 10% O(2) for 14 days. Levels of markers for oxidative stress (malondialdhyde) and inflammation (tumor necrosis factor-α (TNFα), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2)) and the expressions of total endothelial NO synthase (eNOS) and phosphorylated eNOS at serine1177 (ser1177) were determined in the lung tissue. We found that the RVSP and the thickness of the arteriolar wall were significantly increased in the vehicle-treated hypoxic animals with elevated levels of malondialdhyde and mRNA expressions of the inflammatory mediators, when compared with the normoxic control. In addition, the phosphorylated eNOS (ser1177) level was significantly decreased, despite an increased eNOS expression in the vehicle-treated hypoxic group. Melatonin treatment significantly attenuated the levels of RVSP, thickness of the arteriolar wall, oxidative and inflammatory markers in the hypoxic animals with a marked increase in the eNOS phosphorylation in the lung. These results suggest that melatonin attenuates pulmonary hypertension by antagonizing the oxidative injury and restoration of NO production.
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spelling pubmed-54859492017-06-29 Melatonin Attenuates Pulmonary Hypertension in Chronically Hypoxic Rats Hung, Ming Wai Yeung, Hang Mee Lau, Chi Fai Poon, Angela Ming See Tipoe, George L. Fung, Man Lung Int J Mol Sci Article Chronic hypoxia induces pulmonary hypertension and vascular remodeling, which are clinically relevant to patients with chronic obstructive pulmonary disease (COPD) associated with a decreased level of nitric oxide (NO). Oxidative stress and inflammation play important roles in the pathophysiological processes in COPD. We examined the hypothesis that daily administration of melatonin (10 mg/kg) mitigates the pulmonary hypertension and vascular remodeling in chronically hypoxic rats. The right ventricular systolic pressure (RVSP) and the thickness of pulmonary arteriolar wall were measured from normoxic control, vehicle- and melatonin-treated hypoxic rats exposed to 10% O(2) for 14 days. Levels of markers for oxidative stress (malondialdhyde) and inflammation (tumor necrosis factor-α (TNFα), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2)) and the expressions of total endothelial NO synthase (eNOS) and phosphorylated eNOS at serine1177 (ser1177) were determined in the lung tissue. We found that the RVSP and the thickness of the arteriolar wall were significantly increased in the vehicle-treated hypoxic animals with elevated levels of malondialdhyde and mRNA expressions of the inflammatory mediators, when compared with the normoxic control. In addition, the phosphorylated eNOS (ser1177) level was significantly decreased, despite an increased eNOS expression in the vehicle-treated hypoxic group. Melatonin treatment significantly attenuated the levels of RVSP, thickness of the arteriolar wall, oxidative and inflammatory markers in the hypoxic animals with a marked increase in the eNOS phosphorylation in the lung. These results suggest that melatonin attenuates pulmonary hypertension by antagonizing the oxidative injury and restoration of NO production. MDPI 2017-05-24 /pmc/articles/PMC5485949/ /pubmed/28538666 http://dx.doi.org/10.3390/ijms18061125 Text en © 2017 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hung, Ming Wai
Yeung, Hang Mee
Lau, Chi Fai
Poon, Angela Ming See
Tipoe, George L.
Fung, Man Lung
Melatonin Attenuates Pulmonary Hypertension in Chronically Hypoxic Rats
title Melatonin Attenuates Pulmonary Hypertension in Chronically Hypoxic Rats
title_full Melatonin Attenuates Pulmonary Hypertension in Chronically Hypoxic Rats
title_fullStr Melatonin Attenuates Pulmonary Hypertension in Chronically Hypoxic Rats
title_full_unstemmed Melatonin Attenuates Pulmonary Hypertension in Chronically Hypoxic Rats
title_short Melatonin Attenuates Pulmonary Hypertension in Chronically Hypoxic Rats
title_sort melatonin attenuates pulmonary hypertension in chronically hypoxic rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485949/
https://www.ncbi.nlm.nih.gov/pubmed/28538666
http://dx.doi.org/10.3390/ijms18061125
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