title: Anandamide induces endothelium-dependent vasoconstriction and CGRPergic nerve-mediated vasodilatation in the rat mesenteric vascular bed.
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 CB(1)-receptor- and prostanoid-mediated endothelium-dependent vasoconstriction and perivascular capsaicin-sensitive CGRPergic nerve-mediated vasodilatation.
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Tamaki
authors.forename: Hideki
authors.initials: H
authors.lastname: Nawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Takatori
authors.forename: Sakiko
authors.initials: S
authors.lastname: Oda
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sendo
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Zamami
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawasaki
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D002186:Cannabinoids / Q000494:pharmacology*; D063388:Endocannabinoids / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D008642:Mesenteric Veins / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D015740:Calcitonin Gene-Related Peptide; C078814:anandamide