EFFECTS OF TERTATOLOL ON POST-PREJUNCTIONAL AND PREJUNCTIONAL BETA-ADRENOCEPTORS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 233  (3) , 801-809
Abstract
The effects of tertatolol, a .beta.-adrenoceptor blocking drug, on postjunctional and prejunctional .beta. receptors were investigated; canine vascular tissues (saphenous veins, coronary arteries and splenic arteries) and guinea-pig trachea and atria were used. At concentrations < 10-5 M, tertatolol did not alter basal tension or contractile responses to electrical stimulation, norepinephrine, K+ or prostaglandin F2.alpha.; at doses .gtoreq. 10-5 M the drug-evoked contractions which were reduced by phentolamine and were absent in denervated veins. Tertatolol at 105 M and 3 .times. 10-5 M augmented the basal efflux of [3H] norepinephrine in saphenous veins labeled with the 3H-transmitter. In veins, 10-5 M of tertatolol depressed the contractions caused by electrical stimulation without affecting those to exogenous norepinephrine; this concentration of the drug also inhibited the stimulation-induced overflow of [3H]norepinephrine. The .beta. receptor blocking properties of tertatolol were tested and compared its effects with those of propranolol. Tertatolol inhibited, in a concentration-dependent manner, the relaxations caused by isoproterenol in saphenous veins, splenic arteries and coronary arteries, and the relaxations evoked by norepinephrine and epinephrine in coronary arteries; the potency of tertatolol was higher than that of propranolol. In trachea and right atria of the guinea-pig, tertatolol inhibited, in a concentration-dependent manner, the dose-response curves to isoproterenol; the relative potency of tertatolol was higher than that of propranolol. In dog saphenous veins, previously incubated with [3H]norepinephrine, tertatolol (10-7 M) blocked the increased stimulation-evoked overflow of the 3H-transmitter induced by isoproterenol. Tertatolol is a powerful inhibitor of both postjunctional .beta.-1 and .beta.-2 adrenoceptors in canine blood vessels, and in trachea and right atria of the guinea pig; the drug also blocks the prejunctional .beta. receptors located on the adrenergic nerve terminals of the dog saphenous vein. Nonspecific vascular effects of tertatolol could only be demonstrated when concentrations of .gtoreq. 10-5 M were used.