Histamine decreases myogenic tone in rat cerebral arteries by H2-receptor-mediated KV channel activation, independent of endothelium and cyclic AMP

Yagna P.R. Jarajapu, Charlotte Oomen, Victor V. Uteshev-Gaard, Harm J. Knot

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The effect of histamine on the pressure-induced constriction was characterized in rat cerebral arteries and mechanisms were investigated. Rat cerebral arteries were pressurized to 70 mm Hg in an arteriograph and the effect of histamine on myogenic tone was studied. Histamine and amthamine, a selective histamine H2-receptor agonist, concentration-dependently decreased myogenic tone, which was unchanged in the absence of endothelium. 2-(2-aminoethyl) pyridine, a selective histamine H1-receptor agonist, produced concentration-dependent constriction of arteries that was significantly increased in the absence of endothelium. Imetit, a selective histamine H3-receptor agonist, has no effect on myogenic tone. The dilation to histamine was antagonized by tiotidine, a selective antagonist of histamine H2-receptor subtype, giving a pKB of 7.86 that was not altered in the absence of endothelium. The histamine-mediated dilation was significantly antagonized by NF 449, a reversible inhibitor of Gs-protein activation but was not affected by ODQ and SQ 22536. Dilations to histamine and amthamine were accompanied by a decrease in arterial wall calcium measured by fura-2 ratios. The dilation to histamine was significantly reduced by partial depolarization of smooth muscle by 25 mM KCl (control 91 ± 5%, 25 mM KCl 53 ± 5%, P < 0.002) and was not observed in the presence of strongly depolarizing 60 mM KCl. The histamine dilation was not affected by iberiotoxin, barium chloride and glibenclamide but was strongly antagonized by 4-aminopyridine (0.3 mM) and tetraethylammonium chloride (10 mM) (pEC50: control: 5.6 ± 0.1, 4-aminopyridine: 4.1 ± 0.1 (P < 0.001); tetraethylammonium chloride: 3.2 ± 0.2 (P < 0.0001)). These results suggest that histamine-mediated reversal of myogenic tone in rat cerebral arteries is endothelium-independent, mediated by histamine H2-receptor subtype with no involvement of guanylyl cyclase or adenylyl cyclase activation and most likely involves activation of KV potassium channels.

Original languageEnglish
Pages (from-to)116-124
Number of pages9
JournalEuropean Journal of Pharmacology
Volume547
Issue number1-3
DOIs
StatePublished - 10 Oct 2006

Keywords

  • Endothelium
  • Histamine
  • K potassium channels
  • Myogenic tone
  • Rat cerebral artery

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