Melatonin attenuates pulmonary hypertension in chronically hypoxic rats
| Autor: | George L. Tipoe, Man-Lung Fung, Chi Fai Lau, MW Hung, Angela Ming See Poon, HM Yeung |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.disease_cause Antioxidants Rats Sprague-Dawley chemistry.chemical_compound 0302 clinical medicine Enos Hypoxia Lung Spectroscopy Melatonin biology anti-oxidant General Medicine Computer Science Applications medicine.anatomical_structure Anesthesia medicine.symptom medicine.drug medicine.medical_specialty chronic hypoxia inflammation lung injury nitric oxide Hypertension Pulmonary Inflammation Pulmonary Artery Lung injury Article Catalysis Nitric oxide Inorganic Chemistry 03 medical and health sciences Internal medicine medicine Animals Physical and Theoretical Chemistry Molecular Biology business.industry Organic Chemistry medicine.disease biology.organism_classification Pulmonary hypertension Rats Oxidative Stress 030104 developmental biology Endocrinology chemistry Chronic Disease business 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | International Journal of Molecular Sciences; Volume 18; Issue 6; Pages: 1125 International Journal of Molecular Sciences |
| Popis: | 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% O2 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. |
| Databáze: | OpenAIRE |
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