The tracheal nonadrenergic noncholinergic inhibitory system during antigen challenge

This study was undertaken to test the hypothesis that malfunction of the nonadrenergic noncholinergic inhibitory system (NANCIS) induces hyperreactive airways. Antigen sensitized guinea pigs were divided into four groups: (1) antigen challenge (n = 6), (2) 2 min oxyhemoglobin (HbO2) + antigen challenge (n = 5), (3) 27 min HbO2 + antigen challenge (n = 4), and (4) 2 min HbO2 + transmural stimulation (TS) + antigen challenge (n = 6). These animals were sensitized with ovalbumin 10 days before the study. In addition, 12 normal control animals without antigen sensitization were used for comparison. Under artificial ventilation, the anesthetized-paralyzed animals were hourly injected with atropine (0.2 mg/kg) and propranolol (1 mg/kg). Cervical segment of the trachea was converted to a closed tracheal pouch filled with Krebs solution containing also atropine (1 microM) and propranolol (3.5 microM). A change in the pouch pressure (Pp) reflected NANCIS TS- or antigen (5 micrograms) challenge-induced relaxation and/or constriction. HbO2 was used to inhibit NANCIS transmitter. There was no significant difference between normal and sensitized animals in the NANCIS TS-induced relaxation. Antigen challenge resulted in biphasic alteration in Pp, an initial increase and then a decrease after about 7 min. HbO2 pretreatment alone did not potentiate antigen-induced increase in Pp. HbO2 + TS, however, significantly abolished the late relaxation phase after antigen challenge.