Anandamide Induces Endothelium-Dependent Vasoconstriction and CGRPergic Nerve–Mediated Vasodilatation in the Rat Mesenteric Vascular Bed

Journal of Pharmacological Sciences

Sakiko Oda³  Chihiro Tamaki³  Yoshito Zamami²  Hiromu Kawasaki³  Toshiaki Sendo¹  Hideki Nawa¹  Shingo Takatori³ 

[1] Department of Hospital Pharmacy, School of Medicine, Okayama University, Japan;Department of Molecular Design for Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan;Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan

关键词: anandamide;    cannabinoid-1 receptor;    transient receptor potential vanilloid-1;    CGRPergic nerve;    prostanoid;   

DOI  :  10.1254/jphs.11236FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(48)Cited-By(4)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 (CB1)-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.

【 授权许可】

Unknown