The effects of histamine, acetylcholine and 5-hydroxytryptamine on lung mechanics and irritant receptors in the dog.

1. The ability of histamine, acetylcholine, acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) given I.V. and by aerosol to induce reflex bronchoconstriction and to activate lung irritant receptors has been studied in dogs anaesthetized with chloralose. 2. Histamine (four breaths of an aerosol from 0.0625%, 0.125% and 0.25% solutions and 5, 10 and 20 microgram kg-1 I.V.), 5-HT (four breaths of an aerosol from 0.5% or 1.0% solutions and 10, 20 and 40 microgram kg-1 I.V.) produced significant relex changes in RL (total lung resistance). The changes in RL produced by ACh (four breaths of an aerosol from 0.25%, 0.5% and 1.0% solutions, of 5, 10, 20 and 40 microgram kg-1 I.V.) were unaffected by vagal cooling. 3. The falls in Cdyn (dynamic compliance) produced by ACh given by aerosol or I.V. were unaffected by vagal cooling. The falls in Cdyn produced by histamine (10 microgram kg-1 and 40 microgram kg-1 I.V.) and 5-HT (four breaths of an aerosol generated from a 0.5% solution and 20 microgram kg-1 and 40 microgram kg-1 I.V.) were significantly reduced by vagal cooling. 4. Histamine, 5-HT and ACh given by aerosol and I.V. increased lung irritant receptor discharge. Irrespective of the route of administration, for a given change in RL histamine produced a greater increase in irritant receptor discharge than did ACh or 5-HT, which produced similar increases. 5. For a given change in RL, histamine, ACh and 5-HT were more effective in activating lung irritant receptors when given I.V. than by aerosol. 6. The mechanisms of irritant receptor activation by histamine, ACh and 5-HT and the relationship between irritant receptor discharge and reflex bronchoconstriction are discussed.