DECREASE IN THE AIRWAYS NONADRENERGIC NONCHOLINERGIC INHIBITORY SYSTEM IN ALLERGEN SENSITIZED RABBITS

A decrease in the airways' nonadrenergic noncholinergic inhibitory (NANC-i) system is one of the mechanisms that may contribute to allergen-induced changes in neural control within airways. We measured the airways' neurally mediated contractile and relaxant (NANC-i) responses in tracheal segments and left mainstem bronchus (LMB) from normal (control), immune (ragweed sensitized), and immune challenged rabbits. Immune rabbits were sensitized to mixed ragweed extract through parenteral injections from birth, while the immune challenged group had an additional airway exposure to aerosolized ragweed 48 hours prior to the in vitro studies; Neurally mediated contractile responses to electrical field stimulation (EFS) were increased in the immune challenged group, with the increase most significant in tracheal smooth muscle at a stimulation frequency of 20 Hz. To assess NANC-i responses, airway smooth muscle (ASM) segments from these groups were placed in tissue baths containing atropine (10(-6) M) and propranolol (5 x 10(-6) M). After contraction of the tissue with neurokinin A (NKA, 10(-5) M), the NANC-i response to EFS at 20 Hz was measured and reported as the mean (+/- SEM) percent relaxation. No significant differences were seen in the contractile responses of ASM segments to NKA among the three groups. The tracheal segments showed a significantly different NANC-i relaxation response among all groups: in the control group, 29.1 +/- 3.7; in the immune group 15.8 +/- 2.3%; and in the immune challenged group, 2.1 +/- 4.2%. The LMB segments showed significantly different NANC-i responses between the immune challenged group (-3.4 +/- 2.5%) and both the control (13.4 +/- 5.7%) and immune group (9.5 +/- 2.9%). This NANC-i response was not diminished by the nitric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester (10(-4) M). We conclude the exposure to ragweed through the airways in rabbits with tgE to this allergen leads to an enhanced contractile response to EFS and a significant decrease in the airways' NANC-i response when compared with normal or immune rabbit airways. In addition, a significant decrease in NANC-i response occurs in tracheal segments from rabbits after parenteral ragweed immunization alone. This decrease in NANC-i may be one mechanism contributing to the altered airway responsiveness associated with IgE immune states. (C) 1994 Wiley-Liss, Inc.