Role of tachykinins in sulfur dioxide-induced bronchoconstriction in anesthetized guinea pigs

To investigate the role of tachykinin release in mediating the bronchoconstrictive effect of sulfur dioxide (SO2) inhalation, measurements of dynamic lung compliance (Cdyn), total pulmonary resistance (RL), and arterial blood pressure (ABP) were made in anesthetized guinea pigs. Brief exposure (six tidal breaths) to SO2 at concentrations between 500 and 2,000 parts/million resulted in a concentration-dependent increase in RL, decrease in Cdyn, and systemic hypotension. For example, SO2 at 2,000 parts/million induced reversible and reproducible changes in RL, Cdyn, and ABP of 1,041 +/- 234, -60 +/- 6, and -25.8 +/- 4.3% of the baseline values, respectively. Pretreatment with two selective neurokinin- (NK) receptor (NK1 and NK2) antagonists, CP-99994 and SR-48968, resulted in almost complete inhibition of the increase in RL and of the decrease in Cdyn while preserving the decrease in ABP. Antagonism of the NK2 receptor alone resulted in inhibition of the majority of the SO2-induced bronchoconstriction, whereas that of the NK1 and muscarinic receptors did not have a significant effect. We conclude that the release of tachykinins from sensory endings plays a central role in SO2-induced bronchoconstriction in anesthetized guinea pigs, primarily via the activation of the NK2 receptor.