CHOLINERGIC AND ALPHA-ADRENERGIC AUGMENTATION OF HISTAMINE-INDUCED CONTRACTION OF CANINE AIRWAY SMOOTH-MUSCLE

  • 1 January 1981
    • journal article
    • research article
    • Vol. 218  (3) , 582-587
Abstract
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 2 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 the agonists administered by i.v. injection together in the same syringe. Synergism was observed for 0.005 .mu.g/kg to 5.0 .mu.g/kg i.v. of MC and 0.0025 .mu.g/kg to 2.5 .mu.g/kg i.v. of histamine, as measured by change in dynamic compliance (P < 0.01), airway resistance (P < 0.001), isometric tracheal smooth muscle tension (P < 0.01) and duration of the tracheal contractile response (P < 0.005). Synergism was observed for 0.002 .mu.g/kg to 2.0 .mu.g/kg of NE and 0.0025 .mu.g/kg to 2.5 .mu.g/kg of histamine i.v. for airway resistance and dynamic compliance (P < 0.025), isometric tracheal contraction (P < 0.05) and duration of tracheal contraction (P < 0.01). No augmentation was observed for 7 animals receiving NE and MC at any dose and the duration of tracheal contraction to these combined agonists was not greater than additive. The addition of histamine to cholinergic or .alpha.-adrenergic stimulation causes synergistic contraction of airways and augmentation of the duration of contractile response. This effect is specific for histamine, as no augmentation is seen when MC and NE are administered together.

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