Changes And Mechanisms Of Myocardial AMPK Phosphorylation And Glycogen Content In Rats Exposed To Hypobaric Hypoxia

ObjectivePlateau has a great influence on the organisms, mainly due to high altitude hypoxia and cellular energy disorder induced by hypoxia. It's critical to maintain cellular energy balance for the compensatory adaptive response after exposed to hypoxia. Previous study shows that, AMP-activated protein kinase (AMPK) is a cellular energy detector, which closely monitoring the cellular energy use and reserve status. Heart is powerful in the center of the circulatory system, and cardiac function is determined directly by myocardial energy metabolism and reserve status after hypoxia. We detected cardiac function, myocardial AMPK phosphorylation and glycogen content of cardiac tissue during acclimatization. We also measured AMPK phosphorylation and glycogen content of cardiac tissue after exercise during hypoxia. We aimed to get a better understanding of hypoxic myocardial energy metabolism and deepen the knowledge of the mechanisms in the high altitude acclimatization-adaptationMethodsRats were submitted to simulated 5000m of high altitude in a hypobaric chamber, 1 and 30 days were selected for the acute and chronic hypoxia model. SD rats were randomly divided into plain control group, acute hypoxia, chronic hypoxia group (NC, AH, CH). Myocardial glycogen content was determined by anthrone method, cardiac function was measured by cardiac catheter technique,myocardial GLUT4 protein, AMPK and pAMPK, ACC and pACC were detected by Western blot, glycogen synthase and phosphorylase activities were detected by radioisotope method.The exercise model was made by forcing rats to run on the treadmill with following conditions: treadmill grade 10°,speed 15.2m/min, running time 30min. Glycogen content was observed at rest and recovery intervals, so rats were divided into four groups according to time point: rest group, recovery 0h group, recovery 0.5h group, recovery 2h group. Myocardial glycogen content was determined by anthrone method, AMPK and pAMPK were detected by Western blot.Results1. In acute hypoxia, pulmonary artery pressure, systolic pressure and maximal contraction rate of right ventricular were significantly increased, which increased further in chronic hypoxia, meanwhile, Hermann-Willson index and hematocrit increased significantly. Whether acute or chronic hypoxic hypoxia, right ventricular function were significantly increased, whereas no difference in left ventricular systolic pressure and the maximum contraction rate.2. After exposed to 5000m simulated high altitude in hypobaric chamber, regardless of acute or chronic hypoxia, right or left ventricle, AMPK phosphorylation was lower than that of plain control group.3. Regardless of acute or chronic hypoxic hypoxia, right or left ventricle, myocardial glycogen content was significantly increased to the same extent.4. There is no change in glycogen content before and after exercise in normoxia; whereas in acute hypoxia, glycogen content dropped most after the same exercise and in chronic hypoxia, exercise consume glycogen significantly(dropped by 34.5%) but less than that in acute hypoxia group(dropped by 46.1%).5. Exercise can increase phosphoralation level in normoxia, which raised most in acute hypoxia (4 fold), subsequently chronic hypoxia (2.5 fold) while there is only a mild increase in plain control group (30%) after the same exercise.6. Compared with the normal control group, right ventricular myocardial GLUT1 protein expression has no difference while GLUT4 increased greatly, both GLUT1 and GLUT4 protein expression in CH increased significantly.7. There is no significant difference in GP activity in three groups, but GS protein increased in AH and CH.8. Glycogen content do not change before and after exercise in normoxia; but in acute hypoxia, exercise consume the cardiac glycogen most, although the glycogen increased rapidly after 2h postexercise, it did not reach its previous level; In chronic hypoxia, exercise consume glycogen significantly but less than that in acute hypoxia group, the glycogen increased sharply after 2h postexercise and reach its previous level.9. AMPK phosphorylation increased transiently after 30minuts'treadmill exercise in NC, AH and CH groups, but the phosphoralation level recovered the same as previous in the three groups after 0.5h recovery from exercise.Conclusions1. Hypoxia exposure for 1 day or 30 days leads to decrease of myocardial AMPK phosphorylation, which indicates energy balance in the myocardium.2. The elevated myocardial glycogen content may be responsible for the reduction of AMPK phosphorylation.3. Whether in acute or chronic hypoxia, enhanced myocardial glycogen anabolism and nearly no change in catabolism may account for increased myocardial glycogen content.4. After the same workload, myocardial glycogen content in acute and chronic hypoxia recovered differently: slowly in acute hypoxia, and rapidly in chronic hypoxia, during which myocardial AMPK phosphorylation was a transient increase.