Effects of excessive noradrenaline on cardiac mitochondrial calcium transport and oxidative phosphorylation.
Mitochondrial oxidative phosphorylation, calcium transport activity and calcium content were investigated in dog hearts injured by excessive noradrenaline (NA). Diffuse cardiac injury was produced by a 5-hour infusion of NA (2 or 5 micrograms/kg/min), and the injury was evaluated based on ECG and hemodynamic changes. Mitochondrial calcium uptake and binding activities measured in the presence of ATP showed no significant differences between the control and NA groups. However, the calcium content of heart mitochondria isolated from the NA groups, state 3 respiration and the respiratory control index were significantly depressed without any change in the ADP/O ratio. These results suggest that excessive NA causes the intracellular calcium overload and the depression of mitochondrial respiration, and the both of these changes may play a key role in the pathogenesis of myocardial injury through the insufficient control of cytosolic calcium levels.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology* / Q000633:toxicity; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects
D008274:Magnesium; D002118:Calcium; D009638:Norepinephrine