AIRWAY RESPONSES TO CAPSAICIN IN GUINEA-PIGS - ROLE OF NK-1 AND NK-2 NEUROKININ RECEPTORS

The role of NK-1 and NK-2 receptors on the pulmonary responses to caps aicin in guinea pigs was evaluated using intravenous infusion of selec tive nonpeptide antagonists of NK-1 (CP 96345, 300 nmol/kg; and SR 140 333, 300 nmol/kg) and NK-2 (SR 48968, 100 nmol/kg) neurokinin receptor s. Maximal values of pulmonary dynamic elastance (Edyn) and pulmonary resistance (R(L)) after capsaicin infusion were significantly lower in the presence of SR 48968 (p<.005). Morphometric analysis of lungs obt ained by quick-freezing showed significant attenuation of airway contr action and peribronchiolar edema formation in the presence of NK-2 ant agonist (p<.001). When compared to guinea pigs that received only caps aicin, animals that received SR 140333 or CP 96345 showed lower values of Edyn, R(L), airway contraction, and peribronchiolar edema, but onl y the difference in Edyn values was significant. The combination of NK -1 and NK-2 antagonists was not more effective than NK-2 antagonist al one in attenuating capsaicin effects. The results suggest that airway effects of capsaicin, are mainly mediated by activation of NK-2 recept ors, although NK-1 receptors may also play a role.