Mediators and oxygen radicals in hyperpnea-induced airway constriction of guinea pigs

Leukotrienes (LTs), tachykinins (TKs), and oxygen radicals have been sugges ted to be important modulating factors for the hyperpnea-induced bronchocon striction (HIB) of guinea pigs. In this study, we tested the hypothesis tha t LTs and oxygen radicals modulate HIB by triggering TK release. Eighty-fiv e Hartley guinea pigs were divided into four groups: control, dimethylthiou rea (DMTU), FPL 55712, and A63162. DMTU is the scavenger for hydroxyl radic al. FPL 55712 is an antagonist of LT receptor, whereas A63I62 is an inhibit or of lipoxygenase. Each group was further divided into three subgroups: ba seline, hyperpnea, and recovery. Each animal was anesthetized, cannulated, paralyzed, and artificially ventilated. We measured dynamic respiratory com pliance (Crs), maximal expiratory flow at 50% total lung capacity ((V)over dot (max50)) and forced expiratory volume in 0.1 s (FEV0.1) during the base line and recovery periods. Hyperpnea caused significant decreases in Crs, ( V)over dot (max50), and FEV0.1, indicating HIB in the control group. Pretre atment with DMTU, FPL 5712, or A63162 attenuated HIB. Plasma substance P (S P) levels increased progressively during the experiment in all groups. Howe ver, both FPL 55712 and A63162, but not DMTU, significantly decreased SP le vels. Similarly, lung malondialdehyde (MDA) contents increased progressivel y during the experiment in the control group. Neither FPL 55712 nor A63162 significantly affected the increase. On the contrary, DMTU significantly at tenuated the increase in MDA during the recovery period. These results sugg est that inhibition of LTs leads to suppression at SP levels and HIB, where as DMTU attenuates HIB by means of other mechanisms.