We investigated the modification of histamine-induced bronchoconstriction by the H2-antagonist cimetidine in conscious sheep. One hundred breaths of 5% histamine aerosol increased mean (SD) pulmonary resistance (RL) by 5.6 (1.4) cmH2O/1/sec. This increase in RL was completely blocked by intravenous clemastine (0.5 mg), a specific H1-antagonist, indicating that the histamine-induced bronchoconstriction was mediated by H1-receptors. Intravenous cimetidine caused a dose-dependent enhancement of the histamine response between 1 and 1000 mg with a mean peak ΔRL of 15.3 (5) cmH2O/1/sec (P<0.05) at the 1000 mg dose, while it blocked the histamine response at a dose of 2400 mg [ΔRL=1.9 (2) cmH2O/1/sec, p=NS]. This paradoxic effect was not related to an anticholinergic mechanism as intravenous cimetidine (2400 mg) failed to block carbachol-induced (25 breaths of 1% solution) bronchoconstriction. We conclude that in the ovine airway, cimetidine is a selective H2-histamine receptor blocker at lower tissue concentrations, and a combined H2- and H1-histamine receptor blocker at high tissue concentrations.
ASJC Scopus subject areas
- Pharmacology (medical)