Cardiovascular effects of selective agonists and antagonists of histamine H3 receptors in the anaesthetized rat |
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Authors: | G Coruzzi E Gambarelli G Bertaccini H Timmerman |
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Institution: | (1) Institute of Pharmacology, University of Parma, via Gramsci 14, I-43100 Parma, Italy;(2) Leiden-Amsterdam Center for Drug Research, Department of Pharmacochemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, NL-1081 HV Amsterdam, The Netherlands |
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Abstract: | The cardiovascular responses to a series of selective histamine H3 receptor agonists, (R) -methylhistamine, imetit and immepip and selective antagonists, thioperamide, clobenpropit and clophenpropit, were studied in anaesthetized rats. At 0.003–1 mol/kg i.v. doses, H3 agonists failed to produce any significant change in the basal blood pressure and heart rate. Larger doses of (R) -methylhistamine increased the blood pressure and heart rate and higher doses of imetit caused vasodepressor responses and reduced heart rate, whereas immepip proved virtually inactive. While (R) -methylhistamine-induced effects were not blocked by histamine H1-, H2- and H3-receptor antagonists, they were however reduced by idazoxan and propranolol, which indicates that the mechanisms involved are adrenergic. The effects induced by imetit are not related to histamine H3 receptors but are mediated by indirect (via 5HT3 receptors) cholinergic mechanisms, since these effects were prevented by 1 mg/kg i.v. atropine and by 0.1 mg/kg i.v. ondansetron. Similarly, the H3 antagonists per se failed to change basal cardiovascular function up to 10 mol/kg i.v. and only at 30 mol/kg i.v. were marked decreases observed in the blood pressure and heart rate with a significant reduction in the effects of noradrenaline. These data indicate that in anaesthetized rats, histamine H3 receptor activation or blockade has no effect on basal cardiovascular function. The effects recorded after the administration of large doses of (R) -methylhistamine and imetit are clearly unrelated to histamine H3 receptors and should be taken into account when using these compounds as H3 ligands for in vivo experiments. |
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Keywords: | Anaesthetized rat Histamine H3 receptors Blood pressure Heart rate Selective agonists and antagonists |
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