EFFECT OF RUTHENIUM RED ON THE BRONCHOCONSTRICTION INDUCED BY CAPSAICIN AND BY SELECTIVE TACHYKININ RECEPTOR AGONISTS IN ANESTHETIZED GUINEA-PIG

1 The effect of systemic administration of ruthenium red on bronchospasm induced by acetylcholine, capsaicin or selective tachykinin receptor agonists ([Sar9]SP sulfone or [betaAla8]-neurokinin A (NKA)-(4-10) for NK-1 and NK-2 receptors, respectively) was studied in anaesthetized guinea-pigs. 2 The bronchospasm induced by capsaicin was reduced by ruthenium red, which did not affect the response induced by acetylcholine. Atropine, which totally blocked the response to acetylcholine, also partially blocked the bronchospasm induced by capsaicin. 3 The inhibitory action of atropine and ruthenium red on the bronchospasm produced by capsaicin was additive, independently from the order of administration of the two antagonists. 4 Ruthenium red induced an increase in [Sar9]SP sulfone-bronchospasm and a marked enhancement of the bronchomotor response to [betaAla8]]NKA-(4-10). This latter was antagonized by the prior administration of the selective NK-2 receptor antagonist MEN10,376. 5 Pretreatment with guanethidine or propranolol increased the airway constriction induced by [betaAla8]NKA-(4-10). Furthermore, pretreatment with guanethidine prevented the enhancement induced by ruthenium red, showing that activation of NK-2 receptors influences the sympathetic bronchodilator drive to the airways. 6 It is concluded that ruthenium red antagonizes selectively the in vivo excitatory effect of capsaicin in guinea-pig airways. Furthermore, the additivity of the blocking action of ruthenium red and atropine indicates that two distinct mechanisms take place in bronchospastic response to i.v. capsaicin in this species.