Histamine H3 receptors inhibit sympathetic modulation of airway microvascular leakage in allergic guinea pigs.

Histamine H3 receptor modulation of antigen-induced airway microvascular leakage (AML) during sympathetic nerve stimulation was studied in guinea pigs. Intravenous administration of ovalbumin (100 micrograms) to sensitized guinea pigs produced AML that was reduced by electrical stimulation of sympathetic sites in the dorsal medulla. The sympatho-inhibition of this AML was attenuated by the histamine H3 receptor agonist, (R)-alpha-methylhistamine (30 and 100 micrograms/kg). The effect of (R)-alpha-methylhistamine was blocked by i.v. administration of the histamine H3 antagonists, thioperamide (1 and 3 mg/kg), burimamide (1-10 mg/kg) and impromidine (1 and 3 mg/kg). Thioperamide (3 mg/kg) and impromidine (3 mg/kg), but not burimamide (10 mg/kg) blocked the reduction in blood pressure due to (R)-alpha-methylhistamine. These results show that histamine H3 receptors inhibit sympathetic nerves that control the airway vasculature.