Prostaglandin involvement in lung C-fiber activation by substance P in guinea pigs

japplphysiol.01276.2005.—Airway hyperresponsiveness is a car-dinal feature of asthma. Lung C-fiber activation induces central and local defense reflexes that may contribute to airway hyperre-sponsiveness. Initial studies show that substance P (SP) activates C fibers even though it is produced and released by these same C fibers. SP may induce release of other endogenous mediators. Bradykinin (BK) is an endogenous mediator that activates C fibers. The hypothesis was tested that SP activates C fibers via BK release. Guinea pigs were anesthetized, and C-fiber activity (FA), pulmonary insufflation pressure (PIP), heart rate, and arterial blood pressure were monitored before and after intravenous injection of capsaicin (Cap), SP, and BK. Identical agonist challenges were repeated after infusion of an antagonist cocktail of des-Arg9-[Leu8]-BK (103 M, B1 antagonist), and HOE-140 (104 M, B2 antagonist). After antagonist administration, BK increased neithe