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Characterization of the vasorelaxant mechanisms of the endocannabinoid anandamide in rat aorta.
Br J Pharmacol 2007; 152(5):699-708BJ

Abstract

BACKGROUND AND PURPOSE

Studies in isolated preparations of vascular tissue (mainly resistance vessels) provide evidence that anandamide exerts vasorelaxation. The aim of the present work was to further characterize the mechanisms involved in the vascular response induced by anandamide in a conduit vessel, rat aorta.

EXPERIMENTAL APPROACH

Isometric tension changes in response to a cumulative concentration-response curve of anandamide (1 nM-100 micro M) were recorded in aortic rings from male Wistar rats. The involvement of a number of factors in this relaxation was investigated including endothelium-derived vasorelaxant products, cannabinoid and vanilloid receptors (transient potential vanilloid receptor-1 (TRPV1)), release of calcitonin gene-related peptide (CGRP), anandamide metabolism and the membrane transporter for anandamide.

KEY RESULTS

Anandamide caused a significant concentration-dependent vasorelaxation in rat aorta. This vasorelaxation was significantly inhibited by Pertussis toxin, by a non-CB1/non-CB2 cannabinoid receptor antagonist, by endothelial denudation, by inhibition of nitric oxide synthesis or inhibition of prostanoid synthesis via cyclooxygenase-2 (COX-2), by blockade of prostaglandin receptors EP4 and by a fatty acid amino hydrolase inhibitor. Antagonists for CB1, CB2, TRPV1 or CGRP receptors, an inhibitor of the release of endothelium-derived hyperpolarizing factor, and an inhibitor of anandamide transport did not modify the vascular response to anandamide.

CONCLUSIONS AND IMPLICATIONS

Our results demonstrate, for the first time, the involvement of the non-CB1/non-CB2 cannabinoid receptor and an anandamide-arachidonic acid-COX-2 derived metabolite (which acts on EP4 receptors) in the endothelial vasorelaxation caused by anandamide in rat aorta.

Authors+Show Affiliations

Area de Farmacología, Dpto. Ciencias de la Salud III, Facultad Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17704831

Citation

Herradón, E, et al. "Characterization of the Vasorelaxant Mechanisms of the Endocannabinoid Anandamide in Rat Aorta." British Journal of Pharmacology, vol. 152, no. 5, 2007, pp. 699-708.
Herradón E, Martín MI, López-Miranda V. Characterization of the vasorelaxant mechanisms of the endocannabinoid anandamide in rat aorta. Br J Pharmacol. 2007;152(5):699-708.
Herradón, E., Martín, M. I., & López-Miranda, V. (2007). Characterization of the vasorelaxant mechanisms of the endocannabinoid anandamide in rat aorta. British Journal of Pharmacology, 152(5), pp. 699-708.
Herradón E, Martín MI, López-Miranda V. Characterization of the Vasorelaxant Mechanisms of the Endocannabinoid Anandamide in Rat Aorta. Br J Pharmacol. 2007;152(5):699-708. PubMed PMID: 17704831.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of the vasorelaxant mechanisms of the endocannabinoid anandamide in rat aorta. AU - Herradón,E, AU - Martín,M I, AU - López-Miranda,V, Y1 - 2007/08/20/ PY - 2007/8/21/pubmed PY - 2008/2/26/medline PY - 2007/8/21/entrez SP - 699 EP - 708 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 152 IS - 5 N2 - BACKGROUND AND PURPOSE: Studies in isolated preparations of vascular tissue (mainly resistance vessels) provide evidence that anandamide exerts vasorelaxation. The aim of the present work was to further characterize the mechanisms involved in the vascular response induced by anandamide in a conduit vessel, rat aorta. EXPERIMENTAL APPROACH: Isometric tension changes in response to a cumulative concentration-response curve of anandamide (1 nM-100 micro M) were recorded in aortic rings from male Wistar rats. The involvement of a number of factors in this relaxation was investigated including endothelium-derived vasorelaxant products, cannabinoid and vanilloid receptors (transient potential vanilloid receptor-1 (TRPV1)), release of calcitonin gene-related peptide (CGRP), anandamide metabolism and the membrane transporter for anandamide. KEY RESULTS: Anandamide caused a significant concentration-dependent vasorelaxation in rat aorta. This vasorelaxation was significantly inhibited by Pertussis toxin, by a non-CB1/non-CB2 cannabinoid receptor antagonist, by endothelial denudation, by inhibition of nitric oxide synthesis or inhibition of prostanoid synthesis via cyclooxygenase-2 (COX-2), by blockade of prostaglandin receptors EP4 and by a fatty acid amino hydrolase inhibitor. Antagonists for CB1, CB2, TRPV1 or CGRP receptors, an inhibitor of the release of endothelium-derived hyperpolarizing factor, and an inhibitor of anandamide transport did not modify the vascular response to anandamide. CONCLUSIONS AND IMPLICATIONS: Our results demonstrate, for the first time, the involvement of the non-CB1/non-CB2 cannabinoid receptor and an anandamide-arachidonic acid-COX-2 derived metabolite (which acts on EP4 receptors) in the endothelial vasorelaxation caused by anandamide in rat aorta. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/17704831/Characterization_of_the_vasorelaxant_mechanisms_of_the_endocannabinoid_anandamide_in_rat_aorta_ L2 - https://doi.org/10.1038/sj.bjp.0707404 DB - PRIME DP - Unbound Medicine ER -