Propranolol potentiates leukotriene D4-induced bronchoconstriction and enhances antagonism by FPL 55712

Abstract Aerosol LTD 4 -induced bronchoconstriction in anesthetized, spontaneously breathing guinea pigs was potentiated by either pretreatment with propranolol or bilateral adrenalectomy, whereas bilateral vagotomy did not affect the LTD 4 response. The dose-response curve describing LTD 4 -induced changes in dynamic lung compliance (C D Y N ) and pulmonary resistance (R L ) [as reflective indices of bronchochonstriction] was shifted to the left by approximately 20-fold by propranolol. Against an equal degree of LTD 4 -induced bronchoconstriction, the leukotriene antagonist, FPL 55712, had an apparent 20-fold greater potency in propranolol-pretreated animals vis a vis saline-treated controls. The duration of action of aerosol FPL 55712 was similar in both propranolol-treated and saline-treated animals. These results demonstrate that aerosol LTD 4 -induced bronchoconstriction is modulated by an adrenergic compensatory bronchodilator mechanism that is apparently dependent upon the adrenals and independent of vagal influences. Inhibition of the effect of this reflex with propranolol also enhances the apparent potency of an aerosol leukotriene antagonist, FPL 55712, presumably reflecting a constant LTD 4 to antagonist ratio in the saline-treated and propranolol-pretreated guinea pigs.