Abstract
BackgroundRhodiola crenulata is traditionally used as a folk medicine in Tibet for preventing high-altitude illnesses, including sudden cardiac death (SCD). The cardio-protective effects of Rhodiola crenulata root extract (RCE) against hypoxia in vivo have been recently confirmed. However, the way in which RCE produces these effects remains unclear. The present study is designed to confirm the protective effects of RCE on the heart in acute hypobaric hypoxia exposure and examine the mechanisms by which this occurs.MethodsSprague–Dawley (SD) rats were pretreated with or without RCE and then exposed to a simulated altitude of 8000 m in a hypobaric hypoxia chamber for 9 h. The expression of cardiac arginase 1 (Arg-1) and endothelial nitric oxide synthase (eNOS) and the activity of associated signaling pathways was examined.ResultsHypoxia reduced cardiac eNOS phosphorylation and increased Arg-1 expression, but both responses were reversed by RCE pre-treatment. In addition, RCE decreased the hypoxia-induced oxidative stress markers of reactive oxygen species (ROS) production, malondialdehyde (MDA) level, and protein carbonyl content. Furthermore, RCE protected cardiomyocytes from hypoxia-induced cardiac apoptosis and restored the phosphorylation level of AKT and p38 MAPK as well as the superoxide dismutase 2 (SOD2) content in hypoxic animals.ConclusionThe findings provide evidence that the effects of Rhodiola crenulata against altitude illness are partially mediated by modulation of eNOS and Arg-1 pathways in the heart.
Highlights
Rhodiola crenulata is traditionally used as a folk medicine in Tibet for preventing high-altitude illnesses, including sudden cardiac death (SCD)
Rhodiola crenulata root extract (RCE) decreased the expression and activity of arginase 1 (Arg-1) induced by hypobaric hypoxia The expression of cardiac Arg-1 under conditions of hypobaric hypoxia was examined by western blotting
Hypoxia significantly (p < 0.01) increased arginase activity from 0.26 ± 0.02 nmol/min/μl in the control group to 0.49 ± 0.01 nmol/min/μl (Fig. 1c). These results indicate that hypoxia increases both Arg-1 expression and arginase activity in heart tissue
Summary
Rhodiola crenulata is traditionally used as a folk medicine in Tibet for preventing high-altitude illnesses, including sudden cardiac death (SCD). The present study is designed to confirm the protective effects of RCE on the heart in acute hypobaric hypoxia exposure and examine the mechanisms by which this occurs. Acute exposure to high altitude involves a hypobaric hypoxic environment. This may initiate pulmonary arterial vasoconstriction, increased vascular resistance, pulmonary hypertension, and high-altitude pulmonary edema (HAPE) in individuals. These events may even have lethal consequences [1]. In addition to the pulmonary alterations, sudden cardiac death (SCD) is another common cause of death that is associated with vasoconstriction and pulmonary hypertension and even more rapid lethality during high-altitude activities [2]. Many hypoxia-induced disorders, including endothelial dysfunction, pulmonary artery vasoconstriction, and pulmonary hypertension (PH) are highly associated with impairment of the endothelial nitric-oxide synthase
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