Cholinergic and alpha adrenergic augmentation of histamine-induced contraction of canine airway smooth muscle.

The effect of i.v. methacholine (MC) and norepinephrine (NE) in causing synergistic contraction of airways with histamine was studied in 31 anesthetized dogs. Dose-response studies were performed for individual agonists and then with agonists administered together for the same animal. The additive airway contractile response to i.v. MC and histamine and i.v. NE and histamine was less than that obtained for the same doses of these agonists administered by i.v. injection together in the same syringe. Synergism was observed for 0.005 microgram/kg to 5.0 microgram/kg i.v. of MC and 0.0025 microgram/kg i.v. of histamine, as measured by change in dynamic compliance (P less than 0.1), airway resistance (P less than .001), isometric tracheal smooth muscle tension (P less than .01) and duration of the tracheal contractile response (P less than 0.005). Synergism was also observed for 0.002 microgram/kg to 2.0 microgram/kg of NE and 0.0025 microgram/kg to 2.5 microgram/kg of histamine i.v. for airway resistance and dynamic compliance (P less than .025), isometric tracheal contraction (P less than .05) and duration of tracheal contraction (P less than .01). No augmentation was observed for seven animals receiving NE and MC at any dose nor was the duration of tracheal contraction to these combined agonists greater than additive. The addition of histamine to cholinergic or alpha adrenergic stimulation results in synergistic contraction of airways and augmentation of the duration of contractile response. This effect is specific for histamine, since no augmentation is seen when MC and NE are administered together.