Diet restriction plays an important role in the alterations of heart mitochondrial function following exposure of young rats to chronic hypoxia

Male Wister rats aged 4 weeks, were subjected to hypobaric hypoxia (baromet ric pressure 505 hPa, PI,O-2 106 hPa) or to diet restriction (reproducing t he effect of hypoxia-induced anorexia) for 4 weeks. Each group (control, hy poxic, pair-fed, n=16), was divided into two sub-groups housed individually in either normal cages or cages with running wheels allowing evaluation of voluntary activity (n=8 each). The skinned-fibre technique was used to eva luate the functional properties of myofibrillar mitochondria from right and left ventricles in situ. The oxidative fibres from the soleus and diaphrag m muscles were also investigated for comparison. Analysis of variance did n ot detect any significant effect of voluntary running activity. With calori e restriction, the maximal respiratory rate (V-max) in the presence of 1 mM adenosine 5 ' -diphosphate (ADP) in myocardial fibres fell significantly ( by about 25%) but was unchanged in skeletal myocytes. Following hypoxia, V- max in myocardial fibres increased by 25% compared with the calorie restric ted group and in soleus and diaphragm muscle fibres by about 30% compared w ith control. In myocardial fibres of control rats, creatine (20 mM) increas ed the sub-maximal respiratory rate by 80% in the presence of 0.1 mM ADP. U nder calorie restriction or hypoxia the stimulatory effect was significantl y reduced to 34-56%. This alteration was due to a decrease in the apparent Michaelis-Menten constant (K-m) of mitochondrial respiration for ADP evalua ted in the absence of creatine, while the K-m in presence of creatine 20 mM was unchanged. In conclusion, reduced food intake decreased the oxidative capacity (V-max) and the apparent K-m for ADP of mitochondria in both left and right ventricles. Chronic hypoxia per se was responsible for an increas e in the oxidative capacity of all oxidative muscles but did not exert sign ificant effects on the control of respiration by ADP and creatine in myocar dium.