IMPAIRMENT OF NEURAL NITRIC OXIDE-MEDIATED RELAXATION AFTER ANTIGEN EXPOSURE IN GUINEA-PIG AIRWAYS IN-VITRO

Nitric oxide (NO), a neurotransmitter of inhibitory nonadrenergic nonc holinergic (iNANC) nerves in airways, is a radical with a short half-l ife, and its function may be modified by airway inflammation. To test this hypothesis, we examined whether airway allergic inflammation affe cts iNANC responses mediated by NO in guinea pigs in vitro. Animals se nsitized with ovalbumin (OA) were challenged with 0.03% OA (OA group) or saline (saline group) by inhalation on 3 consecutive days. On the d ay after the final challenge, iNANC responses elicited by electrical f ield stimulation (2 to 16 Hz) or relaxation responses to 3-morpholinos ydnonimine (SIN-1), 10(-8) to 10(-4) M, were obtained in the tracheal strips precontracted by histamine (3 x 10(-6) M) in the presence of at ropine and propranolol (both 10(-6) M). The iNANC responses of the OA group were significantly attenuated compared with those of the saline group (p < 0.05), and the inhibitory effect of a NO synthase (NOS) inh ibitor, N-omega-nitro-L-arginine methyl ester, on the iNANC responses was abolished in the OA group. SIN-1-induced tracheal smooth muscle re laxation was also significantly affected by antigen exposure (p < 0.05 ), the effect of which disappeared in the presence of a NO scavenger, carboxy PTIO (3 x 10(-6) M). The impairment of the iNANC responses aft er antigen exposure was significantly restored by superoxide dismutase (1,000 U/ml), especially at lower frequencies. Histochemical demonstr ation of NADPH-diaphorase-positive nerves representing neural NOS dens ity was not different between the two groups. These results suggest th at allergic airway inflammation impairs neural NO-induced relaxation, presumably by inhibiting the access of neural NO to the airway smooth muscle.