On the mechanism of histamine-induced bronchodilation in conscious guinea-pigs.
The bronchodilatory effect of histamine was evaluated in a conscious guinea-pig model of cholinergically mediated bronchoconstriction. The H1, bronchoconstrictor, property of histamine was masked using high doses of the H1-antagonist chlorpheniramine (30 mg/kg), and the bronchodilatory activity evaluated by observing the increase in latency to collapse induced by aerosol methacholine. Under these conditions, histamine (1.0, 3.0 or 10.0 mg/kg, i.p.) delayed methacholine-induced collapse in a dose-dependent manner. Cimetidine, an H2-receptor antagonist (10 to 100 mg/kg), did not delay collapse either in the presence or absence of an H1-antagonist. However, when cimetidine was administered prior to histamine, the bronchodilatory activity of histamine was abolished. A similar abolition of histamine bronchodilation was observed if propranolol, a beta-adrenoceptor antagonist, was administered prior to histamine. Propranolol alone had no effect on methacholine-induced bronchospasm. These data suggest that the major bronchodilatory property of histamine may be mediated indirectly via catecholamine release through an H2-receptor mechanism.
D000336:Aerosols; D000818:Animals; D001986:Bronchial Spasm / Q000139:chemically induced; D001993:Bronchodilator Agents; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D008785:Metiamide / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000187:drug effects
D000336:Aerosols; D001993:Bronchodilator Agents; D006633:Histamine Antagonists; D008688:Methacholine Compounds; D011969:Receptors, Histamine H1; D016210:Methacholine Chloride; D008785:Metiamide; D002744:Chlorpheniramine; D002927:Cimetidine; D006632:Histamine; D011433:Propranolol