CARDIOTONIC ACTION OF RING A-MODIFIED CARDENOLIDES, WITH SPECIAL REFERENCE TO CLEAVAGE OF THE RING

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Abstract
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 of Ascaris antigen (3 mg protein) by inhalation showed increases in respiratory resistance (Rrs) and respiratory rate to 2.5- to 5.0-fold. Airway secretion volume was also significantly increased 3- to 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.) but not by cimetidine. Hypersecretion of tracheobronchial fluid in both asthmas was significantly prevented by 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. Histamine is probably involved in the allergic asthma produced by A. suum. Histamine apparently 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.