The action of beta-adrenoceptor antagonists on rat heart mitochondrial function in vitro: a comparison of propranolol, timolol, and atenolol.

The effect of beta-adrenoceptor antagonists, propranolol, timolol and atenolol on functions of rat heart mitochondria in vitro was investigated. Concentrations of all three drugs less than 2 mmol X litre-1 did not affect rates of respiration of uncoupled intact mitochondria supported by substrates of alpha-oxoglutarate, pyruvate-malate or succinate. Inhibition was observed if mitochondria were broken to allow access of substrates and drugs into the mitochondria. Studies of the effect of drug concentration on NADH-supported oxygen uptake and NADH oxidase activity of submitochondrial particles produced from rat heart mitochondria showed a marked inhibition by propranolol: the effect of timolol and atenolol were much less marked and inhibition was only observed at relatively high concentrations of these drugs. Transfer of electrons through Complex I measured by the rate of reduction of ferricyanide by submitochondrial particles inhibited by rotenone and the lack of specific inhibition by propranolol of succinate supported respiration indicated that one site of drug action was between NADH dehydrogenase and its associated flavoprotein, possibly close to the site of rotenone inhibition.