Impairment of neural nitric oxide-mediated relaxation after antigen exposure in guinea pig airways in vitro.
Nitric oxide (NO), a neurotransmitter of inhibitory nonadrenergic noncholinergic (iNANC) nerves in airways, is a radical with a short half-life, and its function may be modified by airway inflammation. To test this hypothesis, we examined whether airway allergic inflammation affects iNANC responses mediated by NO in guinea pigs in vitro. Animals sensitized with ovalbumin (OA) were challenged with 0.03% OA (OA group) or saline (saline group) by inhalation on 3 consecutive days. On the day after the final challenge, iNANC responses elicited by electrical field stimulation (2 to 16 Hz) or relaxation responses to 3-morpholinosydnonimine (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 atropine 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) inhibitor, Nm-nitro-L-arginine methyl ester, on the INANC responses was abolished in the OA group. SIN-1-induced tracheal smooth muscle relaxation 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 after antigen exposure was significantly restored by superoxide dismutase (1,000 U/ml), especially at lower frequencies. Histochemical demonstration of NADPH-diaphorase-positive nerves representing neural NOS density was not different between the two groups. These results suggest that allergic airway inflammation impairs neural NO-induced relaxation, presumably by inhibiting the access of neural NO to the airway smooth muscle.
Miura
M
M
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Yamauchi
H
H
Ichinose
M
M
Ohuchi
Y
Y
Kageyama
N
N
Tomaki
M
M
Endoh
N
N
Shirato
K
K
D000818:Animals; D001980:Bronchi / Q000737:chemistry / Q000294:innervation*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009252:NADPH Dehydrogenase / Q000032:analysis; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010047:Ovalbumin
D009569:Nitric Oxide; D010047:Ovalbumin; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase