PROPRANOLOL STEREOSELECTIVELY INHIBITS ALPHA-ADRENOCEPTOR-MEDIATED VASOCONSTRICTION MESENTERIC ARTERIAL BEDS OF RATS

1 The optical isomers of propranolol were compared for their effects o n presser responses to adrenergic and non-adrenergic vasoconstrictors in mesenteric arterial beds of rats. 2 R(+)-propranolol (10(-7)-10(-5) M) had no effect on vessel preparations stimulated with noradrenaline , methoxamine, or arginine-vasopressin. 3 S(-)-propranolol 10(-7) M di d not alter presser responses to noradrenaline. However, S(-)-proprano lol 10(-6) and 10(-5) M inhibited vasoconstriction induced by noradren aline. This effect was similar in the presence of indomethacin 3 x 10( -6) M. 4 S(-)-propranolol 10(-5) M also inhibited vasoconstriction ind uced by methoxamine, shifting the dose-response curves to the right, b ut did not affect presser responses to arginine-vasopressin. 5 Schild analysis for equilibrium vasoconstrictor responses to methoxamine indi cated stereoselective competitive alpha-adrenoceptor antagonism by pro pranolol. 6 These data suggest selective inhibition of alpha-adrenocep tor-mediated vasoconstriction by S(-)-propranolol at higher concentrat ions by competitive alpha-adrenoceptor antagonism.