The role of the inhibitory nonadrenergic noncholinergic system in antigen-induced pulmonary hypersensitivity

To study the role of the inhibitory nonadrenergic noncholinergic (i-NANC) system in regulating bronchial reactivity during antigen challenge, we first tested a blocker of the i-NANC system (oxyhemoglobin, HbO(2), 2.5 mu m) on the relaxation response of guinea pig tracheal strips (n=6) in vitro to electrical field stimulation (ES) in the presence of atropine (1 mu g/ml) and propranolol (2 mu g/ml). Fresh HbO(2) significantly inhibited 35.3+/-4.5% (P<0.001) of the NANC relaxation response. Secondary, 26 anesthetized, ovalbumin-sensitized animals were divided into three groups: antigen challenged (n=10), pretreated with HbO(2) (13 mg/kg) and challenged (n=9), and treated with HbO(2) only (n=7), Pulmonary resistance (R-L) and dynamic compliance (Cdyn) were measured 15-20 min prior to (baseline) and up to 30 min after antigen or HbO(2) injection. Antigen challenge alone induced early maximal respiratory changes: R-L increased 1646+/-115% above baseline (2 min) whereas Cdyn decreased 42+/-10% below baseline (4 min). These changes returned to baseline within 15 min, Pretreatment with HbO(2) increased peak respiratory responses induced by antigen [R-L, 3728+/-1680% above baseline; Cdyn, 69+/-7% below baseline (P<0.05)], HbO(2) delayed significantly (P<0.05) the time for recovery of R-L and Cdyn, HbO(2) alone had little effect on respiratory parameters, We conclude that HbO(2) may antagonize the i-NANC system in the airway and this antagonism may accentuate pulmonary hypersensitivity during acute antigen challenge.