Hypobaric hypoxia is an environmental stress leading to high-altitude pulmonary hypertension. While high-altitude pulmonary hypertension has been linked to high hematocrit findings (chronic mountain sickness; CMS). The present study is designed to investigate the effect of arginine (ARG) on hypobaric hypoxia-induced CMS of rats. Hypobaric hypoxia resulted in lower body weight, decreased appetite, increased pulmonary artery pressure, and deteriorated lung tissue damage in rats. Red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin values and blood viscosity were increased in rats, which were alleviated by ARG. microRNA (miRNA) microarray analysis was used to filter differentially expressed miRNAs after ARG in rats. miR-144-5p was reduced under hypobaric hypoxia and upregulated by ARG. miR-144-5p silencing aggravated the erythrocytosis and hyperviscosity in rats, and also accentuated tissue damage and excessive accumulation of RBC. The role of miR-144-5p in rats with CMS was achieved by blocking erythropoietin (EPO)/erythropoietin receptor (EPOR). In conclusion, ARG alleviated CMS symptoms in rodents exposed to hypobaric hypoxia by decreasing EPO/EPOR via miR-144-5p.
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