severe hypoxia can protect cardiac muscles from damage [4,5]. These previous studies suggest the importance of carbohydrate substrate in maintaining normal cardiac function under stress conditions that lower arterial PO 2 .Recently, altitude exercise training in "living hightraining low" fashion has been proposed to improve endurance performance in athletes [6]. The adaptive response of the cardiac muscles associated with glycogen storage under a hypoxia-training regimen has never been investigated. Previous study has shown that exercise, hypoxia, and myocardial ischemia (the acute conditions that reduce arterial PO 2 ) dramatically increase the rate of glucose transport, and this Japanese Journal of Physiology Vol. 54, No. 4, 2004 357 During exercise or hypoxia, carbohydrates become increasingly important as energy metabolism becomes more anaerobic. Under normal conditions, the working heart produces a constant and abundant supply of ATP, mainly relying on fat oxidation [1]. But when the rate of oxygen demand exceeds oxygen supply in the tissue, the ratio of energy reliance on fat will be forced to reduce. In this situation, carbohydrate substrate becomes crucial for sustaining normal tissue function. This is particularly evident in cardiac muscles because hypoxic stress can lead to a significant decrease in glycogen content of the tissue [2,3]. In this respect, it has been shown that interventions that enhance carbohydrate metabolism during Abstract: Altitude training is a common method used to enhance endurance performance in athletes. We have examined the interactive effect of exercise training and chronic hypoxic on glycogen storage and GLUT4 protein expression in cardiac muscles. Thirty-two male SpragueDawley rats were weight balanced and assigned to one of the following four groups: control, exercise, hypoxia, and hypoxia-exercise. Rats with hypoxic treatment (breathing 14% O 2 for 12 hr/d) were exposed under normobaric conditions. The training protocol consisted of swimming for two 3-hr periods per day for 4 weeks. Glycogen content, GLUT4 protein, and mRNA of all rats were determined 16 hr after treatments. Four-week exercise training without hypoxia significantly elevated myocardial glycogen level by 45%. The chronic hypoxic-exercise training elevated the myocardial glycogen level by 67% above control level, significantly greater than the exercise group. Chronic hypoxia, exercise training, and hypoxia-exercise training significantly elevated GLUT4 protein by 40-70% in cardiac muscles. Chronic hypoxia significantly elevates the GLUT1 protein level independent of exercise training.The new finding in this study was that GLUT4 gene expression in cardiac muscle can be stimulated by exercise training with hypoxia treatments. This molecular adaptation appears to be associated with the observed increase in glycogen storage of the muscle.