Mechanism of substance P-induced bronchoconstriction in maturing rabbit

tional effects of substance P (SP) on airway function were quantitatively assessed in 30 anesthetized tracheotomized rab-bits ranging in age from 2 to 29 days. Following paralysis, during mechanical ventilation with 100 % 02 in a body plethys-mograph, respiratory resistance (Rrs) and dynamic compliance (Cdyn) were continuously monitored. Noncumulative systemic infusions of SP (0.001-5.0 pg/g) produced dose-dependent de-creases in pulmonary conductance (Grs), i.e., l/Rrs, and Cdyn. The dose of SP producing a 50 % decrease in Cdyn (PDW-Cdyn) significantly increased as a function of age indicating a dimi-nution in airway sensitivity to SP. Bilateral cervical vagotomy and ganglionic blockade with hexamethonium had no effect on the airway response to SP. On the other hand, the response was significantly reduced following atropine sulfate infusion (2 mg/kg), suggesting a peripheral cholinergic contribution lo