BRONCHODILATOR ACTION OF INHALED NITRIC-OXIDE IN GUINEA-PIGS

The effects of inhaling nitric oxide (NO) on airway mechanics were studied in anesthetized and mechanically ventilated guinea pigs. In animals without induced bronchoconstriction, breathing 300 ppm NO decreased baseline pulmonary resistance (R(L)) from 0.138+/-0.004 (mean+/-SE) to 0.125+/-0.002 cmH2O/ml.s (P < 0.05). When an intravenous infusion of methacholine (3.5-12-mu-g/kg.min) was used to increase R(L) from 0.143+/-0.008 to 0.474+/-0.041 cmH2O/ml.s (P < 0.05), inhalation of 5-300 ppm NO-containing gas mixtures produced a dose-related, rapid, consistent, and reversible reduction of R(L) and an increase of dynamic lung compliance. The onset of bronchodilation was rapid, beginning within 30 s after commencing inhalation. An inhaled NO concentration of 15.0+/-2.1 ppm was required to reduce R(L) by 50% of the induced bronchoconstriction. Inhalation of 100 ppm NO for 1 h did not produce tolerance to its bronchodilator effect nor did it induce substantial methemoglobinemia (< 2%). The bronchodilating effects of NO were additive with the effects of inhaled terbutaline, irrespective of the sequence of NO and terbutaline administration. Inhaling aerosol generated from S-nitroso-N-acetylpenicillamine also induced a rapid and profound decrease of R(L) from 0.453+/-0.022 to 0.287+/-0.022 cmH2O/ml.s, which lasted for over 15 min in guinea pigs bronchoconstricted with methacholine. Our results indicate that low levels of inhaled gaseous NO, or an aerosolized NO-releasing compound are potent bronchodilators in guinea pigs.