Reversal of bronchoconstriction by inhaled nitric oxide. Histamine versus methacholine

Using high-resolution CT (HRCT), which measures changes in innervated airways greater than 1 mm in diameter, we compared the ability of nitric oxide (NO) to dilate airways preconstricted with histamine and methacholine in five anesthetized dogs. After the airways were preconstricted, NO was inhaled in concentrations of 100, 200, and 400 ppm. Additionally, histamine was given with and without atropine and methylene blue. Data were analyzed by one-way analysis of variance. Histamine and methacholine decreased airway area to a similar extent: 60 +/- 3% (mean +/- SEM) and 63 +/- 3% of control, respectively (p = 0.85). Atropine completely reversed the histamine-induced constriction (255 +/- 19%). NO also completely reversed histamine-induced airway constriction in a dose-related fashion. The airway area went from 60 +/- 3% during histamine infusion to 85 +/- 5, 102 +/- 5, and 111 +/- 10% of control, respectively (p < 0.01), after doses of 100, 200, and 400 ppm NO. Methylene blue partially inhibited the reversal by 200 ppm NO of histamine-induced constriction. In contrast, NO only partially reversed methacholine-induced constriction. NO at 100, 200, and 400 ppm partially attenuated the methacholine-induced airway constriction. Airway area went from 63 +/- 3 to 67 +/- 3, 75 +/- 3, and 75 +/- 2% of control, respectively (p < 0.01). We conclude that NO relaxes canine conducting airways by indirect mechanisms as well as by directly relaxing the airway smooth muscle.