α3β4-Nicotinic receptors mediate adrenergic nerve- and peptidergic (CGRP) nerve-dependent vasodilation induced by nicotine in rat mesenteric arteries

S. Eguchi, S. Miyashita, Y. Kitamura, H. Kawasaki

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25 Citations (Scopus)

Abstract

Background and purpose: Previous studies demonstrated that nicotine-induced endothelium-independent vasodilation is mediated by perivascular adrenergic nerves and nerves releasing calcitonin gene-related peptide (CGRPergic nerves). We characterized the nicotinic acetylcholine (ACh) receptor subtype underlying the vasodilation in response to nicotine in rat mesenteric arteries. Experimental approach: Rat mesenteric vascular beds without endothelium were contracted by perfusion with Krebs solution containing methoxamine and the perfusion pressure was measured with a pressure transducer. Key results: Perfusion of nicotine (1-100 μM) for 1 min caused a concentration-dependent decrease in perfusion pressure due to vasodilation. Perfusion of (±)-epibatidine (1-100 nM) (non-selective agonist) or (-)-cytisine (1-100 μM) (partial agonist for nicotinic β2 subtype and full agonist for nicotinic β4 subtype) induced vasodilation in a concentration-dependent manner. Vasodilation induced by nicotine, (-)-cytisine- and (±)- epibatidine was markedly attenuated by guanethidine (5 μM) and pretreatment with capsaicin (1 μM). Mecamylamine (relatively selective antagonist for α3β4 subtype), but not dihydro-β-erythroidine (selective antagonist for α4β2 subtype) or α-bungarotoxin (selective antagonist for α7 subtype), markedly inhibited nicotine-induced vasodilation. Nicotine-induced vasodilation was inhibited by methyllycaconitine at high concentrations (>1 μM), which non-selectively antagonize nicotinic receptors, while a low concentration of 10 nM, which selectively antagonizes α7 subtype, had no effect. (-)-Cytisine and (±)-epibatidine-induced vasodilation were abolished by mecamylamine Conclusion and implications: These results suggest that the nicotinic α3β4 receptor subtype, but not the α7 and α4β2 subtypes, is responsible for the vasodilation in rat mesenteric arteries induced by nicotine- and nicotinic ACh receptor agonists through stimulation of adrenergic and CGRPergic perivascular nerves.

Original languageEnglish
Pages (from-to)1216-1223
Number of pages8
JournalBritish Journal of Pharmacology
Volume151
Issue number8
DOIs
Publication statusPublished - Aug 1 2007

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Keywords

  • Adrenergic nerves
  • Calcitonin gene-related peptide-containing nerves
  • Nicotine
  • Rat mesenteric resistance artery
  • Vasodilation
  • α3β4 nicotinic receptor subtype

ASJC Scopus subject areas

  • Pharmacology

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