Hedner J, Hedner T, Wessberg P, Jonason J
J Pharmacol Exp Ther. 1984 Jan;228(1):196-201.
The effects of substance P (SP) on respiratory regulation were studied in halothane-anesthetized rats. Intracerebroventricular injections of SP in the dose range 3 to 30 micrograms (3 X 10(-9) to 3 X 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 response 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 it was found that maximum pressure indicating inspiratory off-switch threshold mechanisms was increased in vagi-intact animals after SP. Furthermore, 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. It is concluded that SP interacts with the respiratory control system by at least two different mechanisms, bulbopontine time setting and inspiratory off-switch mechanisms. SP may also directly increase central inspiratory activity.
在氟烷麻醉的大鼠中研究了P物质（SP）对呼吸调节的影响。脑室内注射剂量范围为3至30微克（3×10⁻⁹至3×10⁻⁸摩尔）的SP，由于潮气量增加，引起分钟通气量呈剂量依赖性刺激，尽管呼吸频率略有下降。吸气驱动（潮气量/吸气时间；P0.1）增加，而呼吸占空比（吸气时间/总周期持续时间）保持不变。双侧迷走神经切断的动物对脑室内注射SP表现出类似的反应，不同之处在于潮气量的增加不太明显，且吸气时间/总周期持续时间缩短。应用闭塞呼吸技术发现，在给予SP后，迷走神经完整的动物中指示吸气切断阈值机制的最大压力增加。此外，SP改变了迷走神经介导的吸气相长度控制，并导致延髓脑桥吸气时间设定缩短。脑室内注射SP后还观察到双相循环反应，最初有降压作用，随后有轻微升压作用。结论是，SP至少通过两种不同机制与呼吸控制系统相互作用，即延髓脑桥时间设定和吸气切断机制。SP也可能直接增加中枢吸气活动。
