Nitric oxide derived from sympathetic nerves regulates airway responsiveness to histamine in guinea pigs

Abstract

Matsumoto, Koichiro, Hisamichi Aizawa, Shohei Takata, Hiromasa Inoue, Naotsugu Takahashi, and Nobuyuki Hara.Nitric oxide derived from sympathetic nerves regulates airway responsiveness to histamine in guinea pigs. J. Appl. Physiol. 83(5): 1432–1437, 1997.—Nitric oxide (NO), which can be derived from the nervous system or the epithelium of the airway, may modulate airway responsiveness. We investigated how NO derived from the airway nervous system would affect the airway responsiveness to histamine and acetylcholine in mechanically ventilated guinea pigs. An NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) (1 mmol/kg ip) significantly enhanced airway responsiveness to histamine but not to acetylcholine. Its enantiomerd-NAME (1 mmol/kg ip), in contrast, had no effect. Thel-NAME-induced airway hyperresponsiveness was still observed in animals pretreated with propranolol (1 mg/kg iv) and atropine (1 mg/kg iv). Pretreatment with the ganglionic blocker hexamethonium (2 mg/kg iv) completely abolished enhancing effect of l-NAME on airway responsiveness. Bilateral cervical vagotomy did not alter thel-NAME-induced airway hyperresponsiveness, whereas sympathetic stellatectomy completely abolished it. Results suggest that NO that was presumably derived from the sympathetic nervous system regulates airway responsiveness to histamine in guinea pigs.