title: Pharmacological Evidence that Histamine H3 Receptors Mediate Histamine-Induced Inhibition of the Vagal Bradycardic Out-flow in Pithed Rats.
abstract: In vivo stimulation of cardiac vagal neurons induces bradycardia by acetylcholine (ACh) release. As vagal release of ACh may be modulated by autoreceptors (muscarinic M2 ) and heteroreceptors (including serotonin 5-HT1 ), this study has analysed the pharmacological profile of the receptors involved in histamine-induced inhibition of the vagal bradycardic out-flow in pithed rats. For this purpose, 180 male Wistar rats were pithed, artificially ventilated and pre-treated (i.v.) with 1 mg/kg atenolol, followed by i.v. administration of physiological saline (1 ml/kg), histamine (10, 50, 100 and 200 μg/kg) or the selective histamine H1 (2-pyridylethylamine), H2 (dimaprit), H3 (methimepip) and H4 (VUF 8430) receptor agonists (1, 10, 50 and 100 μg/kg each). Under these conditions, electrical stimulation (3, 6 and 9 Hz; 15 ± 3 V and 1 ms) of the vagus nerve resulted in frequency-dependent bradycardic responses, which were (i) unchanged during the infusions of saline, 2-pyridylethylamine, dimaprit or VUF 8430; and (ii) dose-dependently inhibited by histamine or methimepip. Moreover, the inhibition of the bradycardia caused by 50 μg/kg of either histamine or methimepip (which failed to inhibit the bradycardic responses to i.v. bolus injections of acetylcholine; 1-10 μg/kg) was abolished by the H3 receptor antagonist JNJ 10181457 (1 mg/kg, i.v.). In conclusion, our results suggest that histamine-induced inhibition of the vagal bradycardic out-flow in pithed rats is mainly mediated by pre-junctional activation of histamine H3 receptors, as previously demonstrated for the vasopressor sympathetic out-flow and the vasodepressor sensory CGRPergic (calcitonin gene-related peptide) out-flow.
authors: Laboratory of Pharmacology, Department of Physiology and Pharmacology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain.
authors: Mónica
authors: M
authors: García
authors: Laboratory of Pharmacology, Department of Physiology and Pharmacology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain.
authors: José Ángel
authors: JÁ
authors: García-Pedraza
authors: Department of Pharmacobiology, Cinvestav-Coapa, México D.F, Mexico.
authors: Carlos M
authors: CM
authors: Villalón
authors: Laboratory of Pharmacology, Department of Physiology and Pharmacology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain.
authors: Asunción
authors: A
authors: Morán
mesh_terms: D000818:Animals; D001919:Bradycardia / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000378:metabolism; D017442:Histamine Agonists / Q000494:pharmacology*; D054828:Histamine H3 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
chemical_list: D017442:Histamine Agonists; D054828:Histamine H3 Antagonists; D007093:Imidazoles; D010880:Piperidines; D011725:Pyridines; D018100:Receptors, Histamine H3; C000596689:methimepip; D006632:Histamine; C006183:2-(2-aminoethyl)pyridine