ACTIVATION OF CAPSAICIN-SENSITIVE SENSORY FIBERS MODULATES PAF-INDUCED BRONCHIAL HYPERRESPONSIVENESS IN ANESTHETIZED GUINEA-PIGS

In anesthetized guinea pigs, a slow intravenous infusion of platelet a ctivating factor (PAF) (600 ng/kg over 1 h) but not of the carrier mol ecule bovine serum albumin (0.25%) induced immediate and transient bro nchoconstriction and a fall in arterial blood pressure followed by an increase in bronchial responsiveness to histamine (0.56 to 1.8 mug/kg intravenously). Pretreatment of guinea pigs with capsaicin (55 mg/kg s ubcutaneously over 2 days) 1 wk before the experiments, or with ruthen ium red (5 mg/kg subcutaneously) 1 h before, completely inhibited caps aicin (2.5 mug/kg intravenously)-induced bronchoconstriction, and comp letely inhibited PAF-induced bronchial hyperresponsiveness. On the oth er hand, PAF-induced immediate bronchoconstriction and decreases in me an arterial blood pressure were not affected by capsaicin and/or ruthe nium red pretreatment. However, pretreatment of guinea pigs with the P AF antagonist WEB 2086 resulted in a complete inhibition of PAF-induce d direct bronchoconstriction, fall in arterial blood pressure, and bro nchial hyperresponsiveness to histamine. It is suggested that in the g uinea pig, PAF-induced bronchial hyperresponsiveness to histamine may be secondary to the activation of capsaicin-sensitive sensory fibers.