H2 receptor blockade and bronchial hyperreactivity to histamine in asthma.

The role of histamine H1 and H2 receptors in the lung is not clear. H1 receptor blockade results in bronchodilatation and inhibition of histamine induced bronchoconstriction. H2 receptor blockade in vitro prevents the normal negative feedback of histamine on further mediator release in antigen challenge. Bronchospasm in guinea pigs given antigen challenge is enhanced by previous administration of metiamide or burimamide but not of cimetidine. These findings suggest the possible deleterious effect of H2 receptor antagonists in asthmatic subjects. The effects of H2 receptor blockade with cimetidine on bronchial hyperreactivity to histamine were studied in 10 asthmatic volunteers by whole body plethysmography. Cimetidine 800 mg and placebo were administered orally on two separate days, eight hours and two hours before study. No significant difference in baseline levels of airways obstruction was seen with the two agents. Inhalational challenge with increasing concentrations of histamine revealed no significant difference in bronchial hyperreactivity to histamine between cimetidine and placebo treatment days. H2 receptor blockade with cimetidine does not appear to affect ventilatory function or bronchial hyperreactivity to histamine in asthmatic subjects. It has been suggested that cimetidine may have H1 as well as H2 receptor blocking properties which prevent this effect.