{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T18:41:18Z","timestamp":1772908878639,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,9,14]],"date-time":"2015-09-14T00:00:00Z","timestamp":1442188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["219707\u2010M"],"award-info":[{"award-number":["219707\u2010M"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>In vivo<\/jats:italic> stimulation of cardiac vagal neurons induces bradycardia by acetylcholine (<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h) release. As vagal release of <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h may be modulated by autoreceptors (muscarinic M<jats:sub>2<\/jats:sub>) and heteroreceptors (including serotonin 5\u2010HT<jats:sub>1<\/jats:sub>), this study has analysed the pharmacological profile of the receptors involved in histamine\u2010induced inhibition of the vagal bradycardic out\u2010flow in pithed rats. For this purpose, 180 male Wistar rats were pithed, artificially ventilated and pre\u2010treated (i.v.) with 1\u00a0mg\/kg atenolol, followed by i.v. administration of physiological saline (1\u00a0ml\/kg), histamine (10, 50, 100 and 200\u00a0\u03bcg\/kg) or the selective histamine H<jats:sub>1<\/jats:sub> (2\u2010pyridylethylamine), H<jats:sub>2<\/jats:sub> (dimaprit), H<jats:sub>3<\/jats:sub> (methimepip) and H<jats:sub>4<\/jats:sub> (VUF 8430) receptor agonists (1, 10, 50 and 100\u00a0\u03bcg\/kg each). Under these conditions, electrical stimulation (3, 6 and 9\u00a0Hz; 15\u00a0\u00b1\u00a03\u00a0V and 1\u00a0ms) of the vagus nerve resulted in frequency\u2010dependent bradycardic responses, which were (i) unchanged during the infusions of saline, 2\u2010pyridylethylamine, dimaprit or VUF 8430; and (ii) dose\u2010dependently inhibited by histamine or methimepip. Moreover, the inhibition of the bradycardia caused by 50\u00a0\u03bcg\/kg of either histamine or methimepip (which failed to inhibit the bradycardic responses to i.v. bolus injections of acetylcholine; 1\u201310\u00a0\u03bcg\/kg) was abolished by the H<jats:sub>3<\/jats:sub> receptor antagonist JNJ\u00a010181457 (1\u00a0mg\/kg, i.v.). In conclusion, our results suggest that histamine\u2010induced inhibition of the vagal bradycardic out\u2010flow in pithed rats is mainly mediated by pre\u2010junctional activation of histamine H<jats:sub>3<\/jats:sub> receptors, as previously demonstrated for the vasopressor sympathetic out\u2010flow and the vasodepressor sensory CGRPergic (calcitonin gene\u2010related peptide) out\u2010flow.<\/jats:p>","DOI":"10.1111\/bcpt.12475","type":"journal-article","created":{"date-parts":[[2015,8,24]],"date-time":"2015-08-24T16:58:49Z","timestamp":1440435529000},"page":"113-121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacological Evidence that Histamine H<sub>3<\/sub> Receptors Mediate Histamine\u2010Induced Inhibition of the Vagal Bradycardic Out\u2010flow in Pithed 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