Protection by /3-Blocking Agents Against Free Radical-Mediated Sarcolemmal Lipid Peroxidation

The effects of ^-blocking and class I antiarrhythmic agents on free radical-mediated sarcolemmal lipid peroxidation were examined. Highly purified canine myocytic sarcolemmal membranes were pretreated with 10-800 /iM of selected ^-blocking (propranolol, pindolol, metoprolol, atenolol, or sotalol) and class I (quinidine, lidocaine, procainamide, or diphenylhydantoin) antiarrhythmic agents at 37° C for 10 minutes. Subsequently, a superoxide radical (derived from dihydroxyfumarate) driven, Fe-ADP catalyzed free radical generating system was added and incubated for up to 45 minutes. Lipid peroxidation of sarcolemma was determined by malondialdehyde formation. Pretreatment of the membranes with the five /J-blockers resulted in various degrees (20-95%) of inhibition of sarcolemmal peroxidation in a concentrationand time-dependent manner. All the class I agents were less effective (<20% inhibition). The order of potency of the 0-blockers was propranolol>pindolol>metoprolol> atenolol>sotalol and appeared to relate to their degree of lipophih'city. Propranol, the most potent agent, achieved half-maximal inhibition of peroxidation at about 100 ftM and achieved significance (p<0.01) at 20 juM. At pH 6.0, the efficacy of pindolol, metoprolol, atenolol, and sotolol diminished by 30-50% compared to pH 7.2, but the potency of propranolol remained unchanged. Since increased free radical production may occur during myocardial ischemia/reperfusion injury, the above findings suggest that the lipophilic 0-blockers may provide additional antiperoxidative protection of ischemic tissue. (Circulation Research 1988;63:262-266)