Activation of capsaicin-sensitive sensory fibers modulates PAF-induced bronchial hyperresponsiveness in anesthetized guinea pigs

Abstract

In anesthetized guinea pigs, a slow intravenous infusion of platelet activating factor (PAF) (600 ng/kg over 1 h) but not of the carrier molecule bovine serum albumin (0.25%) induced immediate and transient bronchoconstriction and a fall in arterial blood pressure followed by an increase in bronchial responsiveness to histamine (0.56 to 1.8 microgram/kg intravenously). Pretreatment of guinea pigs with capsaicin (55 mg/kg subcutaneously over 2 days) 1 wk before the experiments, or with ruthenium red (5 mg/kg subcutaneously) 1 h before, completely inhibited capsaicin (2.5 micrograms/kg intravenously)-induced bronchoconstriction, and completely inhibited PAF-induced bronchial hyperresponsiveness. On the other hand, PAF-induced immediate bronchoconstriction and decreases in mean arterial blood pressure were not affected by capsaicin and/or ruthenium red pretreatment. However, pretreatment of guinea pigs with the PAF antagonist WEB 2086 resulted in a complete inhibition of PAF-induced direct bronchoconstriction, fall in arterial blood pressure, and bronchial hyperresponsiveness to histamine. It is suggested that in the guinea pig, PAF-induced bronchial hyperresponsiveness to histamine may be secondary to the activation of capsaicin-sensitive sensory fibers.