Histaminergic mechanisms involved in the centrally mediated effects of ouabain.
The role of central histaminergic mechanisms in cardiac glycoside toxicity was evaluated in chloralose-urethane anesthetized cats. Cardiac rhythm, blood pressure and sympathetic nerve activity were monitored during continuous i.v. infusion of ouabain (1 microgram/kg/min). Histamine administered into the fourth cerebral ventricle decreased significantly the dose of ouabain necessary to produce ventricular arrhythmias and fibrillation. Toxicity potentiation was associated with enhancement of sympathetic efferent activity. Dimaprit, a specific H2 receptor agonist, produced a similar, but slightly greater, potentiation of ouabain activity than histamine when similarly administered. Intracerebroventricular (i.c.v.) pretreatment of cats with cimetidine, an H2 receptor antagonist, provided a dose-dependent protective effect against ouabain-induced toxicity. Central administration of diphenhydramine, an H1 receptor antagonist, had no effect on cardiotoxic actions. These results suggest a role for central histaminergic mechanisms in cardiac glycoside toxicity which is mediated through an H2 receptor process. Furthermore, it is suggested that ouabain stimulates central histaminergic neurons which impinge on hypothalamic areas and such excitement results in a centrogenic activation of sympathetic centers which is responsible for cardiac glycoside cardiotoxicity.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002415:Cats; D005260:Female; D006632:Histamine / Q000008:administration & dosage / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects*; D008297:Male; D010042:Ouabain / Q000633:toxicity*; D011968:Receptors, Histamine / Q000187:drug effects*; D011970:Receptors, Histamine H2 / Q000187:drug effects*
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D010042:Ouabain; D006632:Histamine