Relaxant effect of aspirin-like drugs on isolated guinea pig tracheal chain.

The interrelation of the inhibitory effect of aspirin-like drugs on the resting tonus of tracheal chain in guinea pigs, arachidonic acid-induced contraction in rat stomach fundus strips and bradykinin-induced bronchoconstriction in guinea pigs in vivo was investigated. All the drugs tested produced a dose-related inhibitory action on the resting tonus of the tracheal chain in comparatively low doses. Diclofenac was the most potent of all the drugs and was equal in activity to isoproterenol, followed in descending order by flufenamic acid, mefenamic acid, indomethacin, ibuprofen, phenylbutazone, oxyphenbutazone and aspirin. These aspirin-like drugs also inhibited arachidonic acid-induced contraction in rat stomach fundus strips. A highly significant correlation was observed between the potency of inhibition of the arachidonic acid-induced contraction and the relaxant effect on the tracheal chain. Moreover, the drugs antagonized bradykinin-induced bronchoconstriction in guinea pigs in vivo and the order of potency roughly paralleled that of the tracheal chain. These results suggest that the aspirin-like drugs produce a reduction in resting tonus of the isolated guinea pig tracheal chain by inhibition of intramural biosynthesis of prostaglandin endoperoxides.