title: Increased airway osmolarity inhibits the action of nitric oxide in the rabbit.
abstract: Inhalation of nitric oxide (NO) is known to dilate preconstricted airways. In asthmatics, there are large variations in the effect of NO on airway tone. One explanation of these variations may be different degrees of airway wall oedema. The effect of NO inhalation on methacholine (meth)-induced airway constriction was investigated in a rabbit model. Oedema and a change in osmolarity of the airways was achieved by hypertonic saline nebulization and hyperventilation with dry gas. There was an increase in resistance to meth at a concentration of 3 mg x mL(-1), of 86+/-14 cmH2O x L(-1) x s (mean+/-SEM) after oedema formation, compared with 46+/-16 cmH2O x L(-1) x s without oedema. Inhalation of 80 parts per million (ppm) NO failed to counter the increase in resistance due to meth, 92+/-14 cmH2O x L(-1) x s after hypertonic saline nebulization. After hyperventilation of dry gas, the increase in resistance due to meth at 1 mg x mL(-1) was 27+/-11 cmH2O x L(-1) x s with 80 ppm NO and 28+/- 5 cmH2O x L(-1) x s without NO. In conclusion, the relaxant effect of nitric oxide-inhalation on the airway smooth muscle can be blocked by an increase in the osmolarity of the airway surface liquid. The mechanism of this inhibition of nitric oxide remains to be established.
authors.affiliation: Dept of Clinical Physiology, University Hospital and Asthma Research Centre, University of Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Högman
authors.forename: J
authors.initials: J
authors.lastname: Hjoberg
authors.forename: G
authors.initials: G
authors.lastname: Hedenstierna
mesh_terms: D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001980:Bronchi / Q000378:metabolism*; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D009994:Osmolar Concentration; D011817:Rabbits; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage
chemical_list: D000336:Aerosols; D016085:Bronchoconstrictor Agents; D012462:Saline Solution, Hypertonic; D016210:Methacholine Chloride; D009569:Nitric Oxide