The effect of inhaled hexamethonium bromide and atropine sulphate on airway responsiveness to histamine.
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.
O'Byrne
P M
PM
Thomson
N C
NC
Latimer
K M
KM
Roberts
R S
RS
Morris
M M
MM
Daniel
E E
EE
Hargreave
F E
FE
D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001285:Atropine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D005541:Forced Expiratory Volume; D006339:Heart Rate / Q000187:drug effects; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000503:physiopathology*; D008297:Male; D010275:Parasympathetic Nervous System / Q000503:physiopathology
D006584:Hexamethonium Compounds; D018738:Hexamethonium; D001285:Atropine; D006632:Histamine