title: Inhaled nitric oxide attenuates bronchoconstriction in canine peripheral airways.
abstract: Inhaled nitric oxide has been proposed as a bronchodilator because it relaxes vascular and airway smooth muscle and attenuates cholinergic reflexes. Although inhaled nitric oxide has been shown to act as a bronchodilator in central airways, effects on peripheral airways are largely unknown. To determine whether nitric oxide produces direct relaxation of peripheral airways, we investigated the ability of nitric oxide to attenuate hypocapnia- and acetylcholine-induced constriction in the peripheral airways of anesthetized dogs. Peripheral airway resistance (RP) was measured using a wedged bronchoscope technique. RP was increased by either hypocapnia (0% CO2 through the bronchoscope for 3 min) or by aerosolized acetylcholine (30 to 60 micrograms/ml for 1 to 3 min), in the presence or absence of nitric oxide. Nitric oxide was delivered directly to the lung periphery in the absence of O2. Nitric oxide (14.5 to 250 ppm) attenuated responses to hypocapnia by 38 +/- 0 to 74 +/- 0% (n = 6) and to acetylcholine by 36 +/- 0 to 52 +/- 0% (n = 6). The ability of inhaled nitric oxide (< 100 ppm) to attenuate Rp responses to two different direct-acting stimuli suggests that nitric oxide acts as a bronchodilator in the lung periphery. The mechanism for this effect may involve relaxation of airway and/or vascular smooth muscle.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Gwyn
authors.forename: K S
authors.initials: KS
authors.lastname: Lindeman
authors.forename: C A
authors.initials: CA
authors.lastname: Hirshman
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000280:Administration, Inhalation; D000403:Airway Resistance; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D016857:Hypocapnia / Q000503:physiopathology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001993:Bronchodilator Agents; D009569:Nitric Oxide; D000109:Acetylcholine