Ventilatory Arrest Evoked by Activation of Bronchopulmonary C‐fibers (PCFs) During Acute Hypoxia Depends on Neurons Containing Neurokinin A Receptor (NK1R) within the Commissural Subnucleus of the Nucleus Tractus Solitaries (cNTS).

Acute hypoxia promotes substance P (SP) release in the NTS, and local SP prolongs the PCF‐mediated apnea via acting on NK1R. Acute hypoxia amplifies PCF‐mediated apnea, leading to a long‐lasting ventilatory arrest (VA) in anesthetized rats (Xu, et al., JAP, 2003). We hypothesized that acute hypoxia increased cNTS SP that amplified the PCF‐mediated apnea to produce the VA via activating NK1R neurons. Three series of experiments were performed. First, the animals were exposed to either room air (RA) for 40 min or five episodes of 10% O2 (HYP, 3 min for each) with a 5‐min interval between two episodes. The mRNA and protein levels of SP in the vicinity of the cNTS were analyzed by using in situ hybridization and EIA, respectively. As compared to RA, HYP significantly increased SP mRNA and protein levels in the cNTS by approximately threefold. Second, the ventilatory responses to right atrial injection of CAP (0.25 (g) after 1 min 10% O2 (CAP + HYP) were compared before and after bilateral microinjection of CP 96345 (1mM, 50 nl), an antagonist of NK1R, into the cNTS. This injection eliminated the VA response to CAP + HYP. Finally, bilateral microinjection (100 nl) of SP‐saporin conjugate (SP‐SAP) into the cNTS to selectively destroy the local neurons containing NK1R and SAP (control) was performed in two groups of rats, respectively. The majority of cNTS NK1R neurons were destroyed 18 days later. This lesion did not significantly change baseline cardiorespiratory variables, but abolished the VA response to CAP + HYP. These data suggest that acute hypoxia significantly elevates cNTS SP, and the latter stimulates local neurons via acting on NK1R, leading to the VA. (Supported by NIH 74183).