Involvement of histamine H1- and H2-receptors in induced asthmas in dogs.
Participation of histamine H1- and H2-receptors in both asthmas, i.e. experimentally induced bronchoconstriction and bronchosecretion, with ascaris suum and histamine in anesthetized dogs was investigated. Dogs given 0.2% histamine solution or ascaris antigen (3 mg protein) by inhalation showed increases in respiratory resistance (Rrs) and respiratory rate to 2.5-5.0 fold. Airway secretion volume was also significantly increased 3-4 fold. The increase in Rrs by histamine inhalation was effectively inhibited or abolished by a histamine H1-receptor antagonist, chlorpheniramine (0.3-1 mg/kg i.v.), but not by a H2-receptor antagonist, cimetidine (1-3 mg/kg i.v.). The increase in Rrs by antigen inhalation was reduced by relatively high doses of chlorpheniramine (1-3 mg/kg i.v.), and not by cimetidine. In contrast, hypersecretion of tracheobronchial fluid in both asthmas was significantly prevented by either chlorpheniramine or cimetidine. Combinations of both antagonists abolished the hypersecretion. Atropine (2 mg/kg i.v.) significantly inhibited the occurrence of responses in both asthmas. The results suggest that histamine is involved in the allergic asthma produced by ascaris suum and that histamine directly evokes airway constriction through H1-receptors and hypersecretion of tracheobronchial fluid through H1- and H2-receptors, and, in part, indirectly activates the cholinergic pathway.
Involvement of histamine H1- and H2-receptors in induced asthmas in dogs. Participation of histamine H1- and H2-receptors in both asthmas, i.e. experimentally induced bronchoconstriction and bronchosecretion, with ascaris suum and histamine in anesthetized dogs was investigated. Dogs given 0.2% histamine solution or ascaris antigen (3 mg protein) by inhalation showed increases in respiratory resistance (Rrs) and respiratory rate to 2.5-5.0 fold. Airway secretion volume was also significantly increased 3-4 fold. The increase in Rrs by histamine inhalation was effectively inhibited or abolished by a histamine H1-receptor antagonist, chlorpheniramine (0.3-1 mg/kg i.v.), but not by a H2-receptor antagonist, cimetidine (1-3 mg/kg i.v.). The increase in Rrs by antigen inhalation was reduced by relatively high doses of chlorpheniramine (1-3 mg/kg i.v.), and not by cimetidine. In contrast, hypersecretion of tracheobronchial fluid in both asthmas was significantly prevented by either chlorpheniramine or cimetidine. Combinations of both antagonists abolished the hypersecretion. Atropine (2 mg/kg i.v.) significantly inhibited the occurrence of responses in both asthmas. The results suggest that histamine is involved in the allergic asthma produced by ascaris suum and that histamine directly evokes airway constriction through H1-receptors and hypersecretion of tracheobronchial fluid through H1- and H2-receptors, and, in part, indirectly activates the cholinergic pathway.