title: Histamine H3 and H4 receptor ligands modify vascular histamine levels in normal and arthritic large blood vessels in vivo.
abstract: Growing evidence associates histamine with arthritis, but its implication in shaping vascular function in chronic inflammation remains largely elusive. This study explored the involvement of vascular histamine in the extra-articular responses in peripheral large blood vessels using a rat model of adjuvant-induced arthritis. Histamine levels were increased in the abdominal aorta and the inferior vena cava of arthritic animals. Contrary to the H1 receptor antagonist dimetindene, histamine induction was observed following administration of the H3 and H4 receptor ligands GSK334429 and JNJ7777120, respectively. In arthritis, prophylactic treatment with GSK334429 partially attenuated the clinical signs and restored basal histamine levels only in the abdominal aorta. This study is the first to implicate the H3 and H4 receptors in a concerted constitutive regulation of basal vascular histamine in the rat large blood vessels and to identify the H3 receptor as a component that may influence arterial histamine during the onset of arthritis.
authors.affiliation: Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kyriakidis
authors.forename: Evangelia
authors.initials: E
authors.lastname: Zampeli
authors.forename: Marina
authors.initials: M
authors.lastname: Palaiologou
authors.forename: Dina
authors.initials: D
authors.lastname: Tiniakos
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Tiligada
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001011:Aorta / Q000473:pathology*; D001169:Arthritis, Experimental / Q000473:pathology*; D001381:Azepines / Q000627:therapeutic use; D004115:Dimethindene / Q000627:therapeutic use; D004727:Endothelium / Q000378:metabolism; D005620:Freund's Adjuvant; D006632:Histamine / Q000097:blood / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000627:therapeutic use; D054828:Histamine H3 Antagonists / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D007249:Inflammation / Q000473:pathology; D008297:Male; D010879:Piperazines / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D011968:Receptors, Histamine / Q000378:metabolism*; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D000074040:Receptors, Histamine H4; D014682:Vena Cava, Inferior / Q000473:pathology*
chemical_list: C519817:1-(1-methylethyl)-4-((1-(6-(trifluoromethyl)-3-pyridinyl)-4-piperidinyl)carbonyl)hexahydro-1H-1,4-diazepine; D000893:Anti-Inflammatory Agents; D001381:Azepines; D006634:Histamine H1 Antagonists; D054828:Histamine H3 Antagonists; C498828:Hrh4 protein, rat; D007211:Indoles; D010879:Piperazines; D011725:Pyridines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D018100:Receptors, Histamine H3; D000074040:Receptors, Histamine H4; C484309:1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine; D004115:Dimethindene; D006632:Histamine; D005620:Freund's Adjuvant