Interrelationship between alpha- and beta-adrenergic agonists and histamine in canine airways

To determine the interrelationship between adrenergic receptors in airway smooth muscle and histamine-induced airway constriction, we studied the responses of 26 parasympathectomized dogs to selective and mixed alpha- and beta-adrenergic stimulation in situ by means of an isometric tracheal smooth-muscle preparation. Intra-arterial (IA) phenylephrine (PE) caused dose-related tracheal contraction beginning at 10-8 mol; maximal active tension was 9.47 +/- 2.2 gm F/cm (mean +/- SD) at 10-5 mol. Pretreatment with propranolol augmented tracheal contraction to PE (maximum 35.5 +/- 3.2 gm F/cm). The contractile response to PE was blocked with a dose of phentolamine (200 microgram/kg IA), which did not alter the response to acetylcholine. Isoproterenol (ISO) caused dose-related tracheal relaxation beginning at 4.2 X 10-11 mol (maximum 43.2 +/- 19.6 gm F/cm). Norepinephrine (NE) also caused tracheal relaxation beginning at 1.2 X 10-6 mol, which was less than relaxation caused by ISO. Prestimulation with histamine did not augment the contractile response to PE but reduced maximal tracheal relaxation to NE ( p less than 0.001). It is concluded that selective alpha-adrenergic stimulation causes tracheal contraction. However, nonselective stimulation results in tracheal relaxation, even with a weak beta-agonist such as NE. Histamine does not augment alpha-adrenergic contraction as previously suggested but causes physiologic antagonism of beta-adrenergic relaxation of tracheal muscle.