The use of an irreversible beta-adrenoreceptor antagonist to examine reserpine- and hypothermia-induced supersensitivity of guinea-pig atria.

1 Positive inotropic and chronotropic responses to guinea-pig isolated left and right atria respectively to the sympathomimetic amine orciprenaline were recorded. 2 Pretreatment of animals with reserpine for 3 days produced supersensitivity of both the inotropic and chronotropic responses. Lowering the bath temperature from 38 degrees to 30 degrees C produced supersensitivity of untreated atria to the inotropic responses only. 3 Irreversible beta-adrenoreceptor antagonism of orciprenaline by Ro 03-7894 was demonstrated by a persistent depression of the maximum inotropic and chronotropic responses after a prolonged washout from the bath (3 h). 4 The depression of the maximum rate and tension responses by Ro 03-7894 was less in atria from reserpine-pretreated animals. 5 The maxima were also depressed less at the lower bath temperature of 30 degrees C. However, when atria were cooled during the incubation with Ro 30-7894, the maxima were still depressed to the 38 degrees C level. 6 That these results suggest either a receptor proliferation or change in efficacy as possible mechanisms for reserpine- and hypothermia-induced supersensitivity is discussed.