title: Activation of the central histaminergic system mediates arachidonic-acid-induced cardiovascular effects.
abstract: The aim of this study was to explain the involvement of the central histaminergic system in arachidonic acid (AA)-induced cardiovascular effects in normotensive rats using hemodynamic, immunohistochemistry, and microdialysis studies. Intracerebroventricularly (i.c.v.) administered AA (0.25, 0.5, and 1.0 μmol) induced dose- and time-dependent increases in mean arterial pressure and decreased heart rate in conscious normotensive Sprague-Dawley rats. Central injection of AA (0.5 μmol) also increased posterior hypothalamic extracellular histamine levels and produced strong COX-1 but not COX-2 immunoreactivity in the posterior hypothalamus of rats. Moreover, the cardiovascular effects and COX-1 immunoreactivity in the posterior hypothalamus induced by AA (0.5 μmol; i.c.v.) were almost completely blocked by the H2 receptor antagonist ranitidine (50 and 100 nmol; i.c.v.) and partially blocked by the H1 receptor blocker chlorpheniramine (100 nmol; i.c.v.) and the H3-H4 receptor antagonist thioperamide (50 and 100 nmol; i.c.v.). In conclusion, these results indicate that centrally administered AA induces pressor and bradycardic responses in conscious rats. Moreover, we suggest that AA may activate histaminergic neurons and increase extracellular histamine levels, particularly in the posterior hypothalamus. Acting as a neurotransmitter, histamine is potentially involved in AA-induced cardiovascular effects under normotensive conditions.
authors: a Department of Physiology, Faculty of Veterinary Medicine, Uludag University, Bursa 16059, Turkey.
authors: Burcin
authors: B
authors: Altinbas
authors: Bora Burak
authors: BB
authors: Topuz
authors: Tuncay
authors: T
authors: İlhan
authors: Mustafa Sertac
authors: MS
authors: Yilmaz
authors: Hatice
authors: H
authors: Erdost
authors: Murat
authors: M
authors: Yalcin
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D002744:Chlorpheniramine / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000378:metabolism* / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D007034:Hypothalamus, Posterior / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D017207:Rats, Sprague-Dawley
chemical_list: D006633:Histamine Antagonists; D018377:Neurotransmitter Agents; D010880:Piperidines; D016718:Arachidonic Acid; D002744:Chlorpheniramine; D006632:Histamine; D011899:Ranitidine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C052075:thioperamide
keywords: acide arachidonique cérébral; brain arachidonic acid; central histaminergic system; cyclooxygenase immunohistochemistry; immunohistochimie de la cyclooxygenase; mean arterial pressure and heart rate; microdialyse; microdialysis; pression artérielle moyenne et rythme cardiaque; système histaminergique central