Altered energy coupling in rat heart mitochondria following in vivo treatment with propranolol.

Effects of acute and chronic treatment with propranolol on oxidative phosphorylation in rat heart mitochondria were examined. Acute propranolol treatment resulted in inhibition of coupled respiration with pyruvate + malate and succinate as substrates. Chronic treatment resulted in decreased state 3 respiration rates with all the substrates employed. The net effect of propranolol treatment was decreased ATP-phosphorylation rates suggesting that this was possibly one of the modes of its cardiodepressant activity. Additionally, chronic propranolol treatment brought about a decrease in the content of cytochrome c + c1 in heart mitochondria. Estimation of propranolol concentrations in serum, whole tissue homogenate and heart mitochondria indicated that although the mitochondria accumulated the highest amount of the drug, the intramitochondrial concentration of the drug was one or two orders of magnitude lower than that which is required to bring about inhibition of respiration under in vitro conditions. Besides, the concentrations reached under acute and chronic treatment conditions were almost comparable. The results, therefore, suggest that the action of the drug in vivo may involve more intricate mechanisms than those observed under in vitro conditions.