[Alpha- and beta-adrenoceptor blocking actions of labetalol and effects on the myocardial function, coronary circulation and myocardial energy metabolism thereof (author's transl)]

Abstract

In the isolated atria, trachea and aorta of the guinea pig and in the heart-lung preparation (HLP) of the dog, labetalol was 3.6 approximately 5.9 times less potent than phentolamine in blocking alpha-adrenoceptors, 1.4 approximately 3.6 times less potent as beta 1-blocker and 6 times less potent as beta 2-blocker than propranolol. Beta 1 and beta 2-blocking actions were 12 approximately 28 and 7 times more potent than alpha-blocking action, respectively. As regards beta 1-blockade, attenuation of the heart rate increase was more prominent than that of the augmentation of the contractile force. Both in the isolated atrial preparation of the guinea pig and in canine HLP, labetalol produced a positive inotropic and chronotropic effect and a slight increase in the coronary flow associated with a slight increase in the myocardial O2 consumption and improvement of the myocardial redox potential. Myocardial extraction and usage of lactate, pyruvate and glucose tended to be decreased and those of FFA decreased significantly. The positive inotropic and chrontropic effect was observed in HLP of 6-hydroxydopamine-pretreated dogs and was abolished with propranolol. Labetalol produced a relaxation of the isolated trachea of the guinea pig, which was inhibited with propranolol. In doses higher than those required for alpha- and beta-adrenoceptor blockade, labetalol produced calcium-antagonistic action.