LIPOPHILIC BETA-BLOCKERS INHIBIT RAT SKELETAL-MUSCLE MITOCHONDRIAL RESPIRATION

Propranolol, metoprolol, acebutolol, nadolol and atenolol were incubat ed with isolated rat skeletal muscle mitochondria at 30-degrees-C, and the rate of oxygen consumption was measured with an oxygen microelect rode. The potency of these drugs to inhibit state III respiration was correlated with lipid solubility as measured by the octanol/water part ition coefficient. The most lipid-soluble beta-blocker, propranolol, h ad an ED50 Of 0.6 mmol/l. The most water-soluble one, atenolol, showed no inhibition at concentrations up to 16 mmol/l. Inhibition of respir atory control ratio, state IV respiration and ADP/0 ratio occurred at 2 mmol/l for propranolol. 16 mmol/I for metoprolol and was not consist ently observed for the other beta-blockers at the concentrations teste d. The inhibition of state III respiration of skeletal muscle mitochon dria by lipid-soluble beta-blockers may be one of the causes of the fa tigue observed in some patients receiving these drugs.