Nitric oxide derived from sympathetic nerves regulates airway responsiveness to histamine in guinea pigs.
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 NG-nitro-L-arginine methyl ester (L-NAME) (1 mmol/kg i.p.) significantly enhanced airway responsiveness to histamine but not to acetylcholine. Its enantiomer D-NAME (1 mmol/kg i.p.), in contrast, had no effect. The L-NAME-induced airway hyperresponsiveness was still observed in animals pretreated with propranolol (1 mg/kg i.v.) and atropine (1 mg/kg i.v.). Pretreatment with the ganglionic blocker hexamethonium (2 mg/kg i.v.) completely abolished enhancing effect of L-NAME on airway responsiveness. Bilateral cervical vagotomy did not alter the L-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.
Matsumoto
K
K
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Aizawa
H
H
Takata
S
S
Inoue
H
H
Takahashi
N
N
Hara
N
N
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005730:Ganglionic Blockers / Q000494:pharmacology; D006168:Guinea Pigs; D018738:Hexamethonium / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects; D013233:Stellate Ganglion / Q000502:physiology; D013564:Sympathetic Nervous System / Q000378:metabolism*; D014628:Vagotomy
D004791:Enzyme Inhibitors; D005730:Ganglionic Blockers; D009569:Nitric Oxide; D018738:Hexamethonium; D006632:Histamine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester