The degree of protection against inhaled
histamine achieved by inhalation of the
ganglion blocker
hexamethonium bromide plus placebo,
hexamethonium plus
atropine sulphate, and placebo plus placebo was examined in six atopic subjects, four of whom had current
asthma.
Hexamethonium was administered until there was systemic evidence of ganglionic blockade with a postural drop in blood pressure of 31 +/- 7.5 mm Hg (mean +/- SD) (p = 0.01) and an increase in heart rate of 30 +/- 3.1 bpm (mean +/- SD) (p = 0.01).
Atropine was inhaled in a dose (18 mg nebulized during tidal breathing) known to produce systemic inhibition of cardiac and salivary
cholinergic (
muscarinic) receptors. The airway effects were measured by FEV1.
Hexamethonium caused bronchoconstriction in all four subjects with
asthma, which was reversed by
atropine. The mean provocation concentration of
histamine to provoke a 20% fall in FEV1 was 2.97 mg/ml after
premedication with placebo, it was not different at 2.84 mg/ml after
hexamethonium alone, and it increased slightly to 5.31 mg/ml after both
hexamethonium and
atropine (p = 0.06). The results suggest that the main effect of inhaled
histamine is not by reflex bronchoconstriction but rather through stimulation of H1-receptors on airway smooth muscle. Therefore,
histamine hyperresponsiveness in
asthma is not primarily caused by a defect in the parasympathetic nervous supply to the airway.