Mechanism of relaxation induced by nicotine in normal and ovalbumin-sensitized guinea-pig trachea.

Nicotine is an irritant molecule in the cigarette that contributes airway hyper-reactivity. The aim of this study was to investigate the mechanism of these effects and effects of nicotine on the isolated trachea preparations from control and ovalbumin-sensitized guinea-pigs. Nicotine (3x10(-5) to 3x10(-4) M) produced concentration-dependent relaxation on isolated trachea preparations precontracted by carbachol (10(-6) M) in both groups. We found that the relaxant effect of nicotine decreased in the presence of N(w)-nitro L-arginine methyl ester (L-NAME) (10(-6) M), and hexamethonium (10(-2) M) but not in the presence of alpha-bungarotoxin (10(-3) M), and tetrodotoxin (3.1x10(-6) M) in isolated trachea preparations in both groups. The relaxant effect of nicotine was less significant in isolated trachea preparations from ovalbumin-sensitized guinea-pigs than from control guinea-pigs (P<0.05). The contractions elicited by carbachol (10(-6) M) were not significantly different in the ovalbumin-sensitized group than in the control group. Nicotine (10(-4) M) significantly increased the cGMP levels in trachea preparations compared with the control preparations.(P<0.05). These results suggest that nicotine-induced relaxation response in normal and ovalbumin sensitized guinea-pigs trachea is at least in part mediated by nitric oxide (NO) since it was significantly reduced in the presence of L-NAME. The decreased relaxation response to nicotine in ovalbumin sensitized guinea-pigs trachea may be due to impaired production and/or liberation of NO.