Sensory receptor activation by mediators of defense reflexes in guinea-pig lungs

Histamine and bradykinin are mediators released within the lungs during lung defense. Both pulmonary rapidly-adapting receptors (RARs) and afferent C-fibers have been suggested to initiate defense reflexes evoked by these mediators. However, it is not known whether the sensory endings are directly stimulated by these mediators rather than indirectly by mechanical changes. Therefore, pulmonary RARs and C-fibers were challenged with aerosols of histamine, bradykinin and capsaicin in anesthetized guinea pigs. During histamine challenge tracheal pressure (PTr) and RAR nerve activity (NA) increased concurrently. After isoproterenol administration to attenuate increases in PTr, histamine-induced increases in RAR NA were similarly attenuated. Results with bradykinin or capsaicin challenge were similar. Therefore activation of RARs by histamine, capsaicin and bradykinin was dependent upon changes in lung mechanics. C-fibers were activated by capsaicin or bradykinin prior to any changes in PTr. However, C-fibers were not affected by histamine challenge despite substantial increases in PTr. C-fibers are activated directly by either capsaicin or bradykinin but not by histamine.