INTERACTION OF SUBSTANCE-P WITH THE RESPIRATORY CONTROL-SYSTEM IN THE RAT

  • 1 January 1984
    • journal article
    • research article
    • Vol. 228  (1) , 196-201
Abstract
The effects of substance P (SP) on respiratory regulation were studied in halothane-anesthetized rats. Intracerebroventricular [i.c.v.] injections of SP in the dose range 3-30 .mu.g (3 .times. 10-9-3 .times. 10-8 mol) induced a dose-dependent stimulation of minute ventilation due to an increase in tidal volume although respiratory frequency was slightly decreased. Inspiratory drive (tidal volume/inspiratory time; P0.1) increased whereas respiratory duty cycle (inspiratory time/total cycle duration) remained unchanged. Animals subjected to bilateral vagotomy showed a similar resposne to i.c.v. SP with the exception that the increase in tidal volume was less pronounced and inspiratory time/total cycle duration was decreased. When applying the occluded breath technique, the maximum pressure indicating inspiratory off-switch threshold mechanisms was increased in vagi-intact animals after SP. SP altered the vagally-mediated control of the length of the inspiratory phase and induced a shortening of the bulbopontine setting for inspiratory time. A biphasic circulatory response with an initial depressor effect followed by a slight pressor effect was also seen after i.c.v. SP. SP evidently interacted with the respiratory control system by at least 2 different mechanisms, bulbopontime time setting and inspiratory off-switch mechanisms. SP may also directly increase central inspiratory activity.