In vivo effect of cimetidine on canine pulmonary responsiveness to aerosol histamine

A series of experiments were designed to discover whether pulmonary histamine H₂ receptors might be of physiologic importance in vivo in the dog. Dose-response curves were performed to aerosol histamine in 11 dogs both before and 1 hr after H₂ receptor blockade with cimetidine (1 mg/kg as a rapid intravenous infusion). Cimetidine had no significant effect on control values of dynamic compliance or resistance of the lung. In the 11 dogs tested H₂ receptor antagonism significantly potentiated (p < 0.05) the animals' pulmonary responsiveness to aerosol histamine. The potentiation of histamine constrictor effects produced by cimetidine were more marked on those dogs initially least responsive to aerosol histamine (p < 0.01). We have found evidence for the presence of inhibitory H₂ receptors in canine airways and for the distribution of these receptors among dogs, explaining in part the previously described differences among dogs in the pulmonary responsiveness to aerosol histamine.