title: Direct effects of inhaled nitric oxide on canine peripheral airways.
abstract: The effects of nitric oxide on peripheral airways in vivo, and whether these effects occur via direct or indirect mechanisms, are unknown. We studied effects of inhaled nitric oxide on histamine-constricted canine peripheral airways in the presence or absence of atropine and an inhibitor of guanylyl cyclase, methylene blue. Peripheral resistance (Rp) was measured by using a wedged-bronchoscope technique in anesthetized dogs. A stable baseline Rp was established. Histamine was infused intravenously, and increasing concentrations of nitric oxide (50-500 ppm) were delivered through the bronchoscope. In separate experiments, histamine was infused intravenously in the presence or absence of atropine (0.2 mg/kg iv) or methylene blue (20 mg/min iv). When Rp stabilized, nitric oxide (500 ppm) was delivered. Nitric oxide partially reversed histamine-induced bronchoconstriction in a dose-dependent fashion (maximum of 42 +/- 3% reduction at 500 ppm; n = 5; P < 0.01) that did not differ in the presence or absence of atropine. Methylene blue blocked the effect of nitric oxide on histamine-induced constriction (n = 6; P = 0.45). These findings suggest that high concentrations of nitric oxide produce small but significant bronchodilation of peripheral airways through a mechanism independent of the cholinergic neural pathway. The mechanism of action appears to involve activation of guanylyl cyclase.
authors.affiliation: Department of Anesthesiology, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Lindeman
authors.forename: A
authors.initials: A
authors.lastname: Aryana
authors.forename: C A
authors.initials: CA
authors.lastname: Hirshman
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006632:Histamine / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012137:Respiratory System / Q000187:drug effects*
chemical_list: D000336:Aerosols; D009569:Nitric Oxide; D001285:Atropine; D006632:Histamine; D006162:Guanylate Cyclase; D000420:Albuterol; D008751:Methylene Blue