title: Diet restriction plays an important role in the alterations of heart mitochondrial function following exposure of young rats to chronic hypoxia.
abstract: Male Wistar rats aged 4 weeks, were subjected to hypobaric hypoxia (barometric pressure 505 hPa, PI,O2 106 hPa) or to diet restriction (reproducing the effect of hypoxia-induced anorexia) for 4 weeks. Each group (control, hypoxic, 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 evaluate the functional properties of myofibrillar mitochondria from right and left ventricles in situ. The oxidative fibres from the soleus and diaphragm muscles were also investigated for comparison. Analysis of variance did not detect any significant effect of voluntary running activity. With calorie restriction, the maximal respiratory rate (Vmax) 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, Vmax in myocardial fibres increased by 25% compared with the calorie restricted group and in soleus and diaphragm muscle fibres by about 30% compared with control. In myocardial fibres of control rats, creatine (20 mM) increased the sub-maximal respiratory rate by 80% in the presence of 0.1 mM ADP. Under calorie restriction or hypoxia the stimulatory effect was significantly reduced to 34-56%. This alteration was due to a decrease in the apparent Michaelis-Menten constant (Km) of mitochondrial respiration for ADP evaluated in the absence of creatine, while the Km in presence of creatine 20 mM was unchanged. In conclusion, reduced food intake decreased the oxidative capacity (Vmax) and the apparent Km for ADP of mitochondria in both left and right ventricles. Chronic hypoxia per se was responsible for an increase in the oxidative capacity of all oxidative muscles but did not exert significant effects on the control of respiration by ADP and creatine in myocardium.
authors.affiliation: Laboratoire de Bioénergétique Fondamentale et Appliquée, Université Joseph Fourier B.P. 53 X, Grenoble, France.
authors.forename: Z
authors.initials: Z
authors.lastname: Daneshrad
authors.forename: V
authors.initials: V
authors.lastname: Novel-Chaté
authors.forename: O
authors.initials: O
authors.lastname: Birot
authors.forename: B
authors.initials: B
authors.lastname: Serrurier
authors.forename: H
authors.initials: H
authors.lastname: Sanchez
authors.forename: A X
authors.initials: AX
authors.lastname: Bigard
authors.forename: A
authors.initials: A
authors.lastname: Rossi
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001274:Atmospheric Pressure; D001835:Body Weight; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003401:Creatine / Q000494:pharmacology; D002149:Energy Intake; D005508:Food Deprivation; D006321:Heart / Q000033:anatomy & histology; D006400:Hematocrit; D000860:Hypoxia / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology*; D018482:Muscle, Skeletal / Q000033:anatomy & histology; D009929:Organ Size; D010101:Oxygen Consumption; D005082:Physical Exertion / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000244:Adenosine Diphosphate; D002950:Citrate (si)-Synthase; D003401:Creatine