Anandamide induces endothelium-dependent vasoconstriction and CGRPergic nerve-mediated vasodilatation in the rat mesenteric vascular bed

Chihiro Tamaki, Hideki Nawa, Shingo Takatori, Sakiko Oda, Toshiaki Sendo, Yoshito Zamami, Hiromu Kawasaki

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

An endogenous cannabinoid anandamide (N-arachidonoylethanolamide) has been shown to cause vasodilatation in vitro and a brief vasoconstriction followed by prolonged depressor response in vivo. This study investigated the vascular effects of anandamide and underlying mechanisms in rat mesenteric vascular beds. In preparations with an intact endothelium and active tone, anandamide at low concentrations (0.1 - 1 nM) caused a concentration-dependent decrease in perfusion pressure due to vasodilatation, but at high concentrations (10 nM - 1 μM) elicited an initial and sharp increase in perfusion pressure due to vasoconstriction followed by long-lasting vasodilatation in a concentration-dependent manner. Treatment with SR141716A [cannabinoid-1 (CB 1)-receptor antagonist] blunted both the vasoconstrictor and vasodilator responses. Also, removal of the endothelium and indomethacin (cyclooxygenase inhibitor), but not adrenergic denervation with 6-hydoxydopamine (adrenergic neurotoxin), markedly inhibited the vasoconstrictor response to anandamide, while these treatments did not affect vasodilatation. The vasodilatation, but not vasoconstriction, in response to anandamide was markedly attenuated by capsazepine [ selective antagonist for transient receptor potential vanilloid-1 (TRPV1)], pretreatment with capsaicin [calcitonin gene-related peptide (CGRP)ergic-nerve depletor], or cold-storage denervation. These results suggest that in rat mesenteric vascular beds, anandamide causes CB1-receptor- and prostanoid-mediated endothelium-dependent vasoconstriction and perivascular capsaicin-sensitive CGRPergic nerve-mediated vasodilatation.

Original languageEnglish
Pages (from-to)496-505
Number of pages10
JournalJournal of Pharmacological Sciences
Volume118
Issue number4
DOIs
Publication statusPublished - 2012

Keywords

  • Anandamide
  • CGRPergic nerve
  • Cannabinoid-1 receptor
  • Prostanoid
  • Transient receptor potential vanilloid-1

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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