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 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.
Perretti
F
F
Pharmacology Department, Istituto Farmacobiologico Malesci s.p.a., Firenze, Italy.
Manzini
S
S
D000758:Anesthesia; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012430:Ruthenium Red / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; D012430:Ruthenium Red; D012710:Serum Albumin, Bovine; D006632:Histamine; D002211:Capsaicin