Endothelium-dependent mechanisms of the vasodilatory effect of the endocannabinoid, anandamide, in the rat pulmonary artery

Baranowska-Kuczko, M., MacLean, M. R., Kozłowska, H. and Malinowska, B. (2012) Endothelium-dependent mechanisms of the vasodilatory effect of the endocannabinoid, anandamide, in the rat pulmonary artery. Pharmacological Research, 66(3), pp. 251-259. (doi:10.1016/j.phrs.2012.05.004)

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Publisher's URL: http://dx.doi.org/10.1016/j.phrs.2012.05.004

Abstract

Endocannabinoids exhibit vasodilatory properties and reduce blood pressure in vivo. However, the influence and mechanism of action of the prominent endocannabinoid, anandamide (AEA), in pulmonary arteries are not known. The present study determined the vascular response to AEA in isolated rat pulmonary arteries. AEA relaxed rat pulmonary arteries that were pre-constricted with U-46619. This relaxation was reduced by the following conditions:removal of the endothelium; in KCl pre-constricted preparations; in the presence of the potassium channel (KCa) blockers, tetraethylammonium and the combination of charybdotoxin and apamin, and the prostacyclin receptor antagonist, RO1138452. Inhibitors of cyclooxygenase (indomethacin), nitric oxide (NO) synthase (NG-nitro-L-arginine methyl ester) and fatty acid amide hydrolase (URB597) alone or in combination diminished AEA-induced relaxation in endothelium-intact vessels. The remaining experiments were performed in the presence of URB597 to eliminate the influence of AEA metabolites. Antagonists of the endothelial cannabinoid receptor (CBx), O-1918 and cannabidiol, attenuated the AEA-induced response. Antagonists of CB1, CB2 and TRPV1 receptors, AM251, AM630 and capsazepine, respectively, did not modify the AEA-induced response. A reference activator of CBx receptors, abnormal cannabidiol, mimicked the receptor-mediated AEA effects. The present study demonstrated that AEA relaxed rat pulmonary arteries in an endothelium-dependent fashion via the activation of the O-1918-sensitive CBx receptor and/or prostacyclin-like vasoactive products of AEA. One or both of these mechanisms may involve KCa or the NO pathway.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:MacLean, Professor Margaret
Authors: Baranowska-Kuczko, M., MacLean, M. R., Kozłowska, H., and Malinowska, B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Pharmacological Research
Publisher:Elsevier
ISSN:1043-6618
ISSN (Online):1096-1186
Published Online:22 May 2012
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
573731Gender and the development of pulmonary arterial hypertension: regulation of genes from mouse to manMargaret MacleanBritish Heart Foundation (BHF)RG/11/7/28916RI CARDIOVASCULAR & MEDICAL SCIENCES
573733Gender and the development of pulmonary arterial hypertension: regulation of genes from mouse to manMargaret MacleanBritish Heart Foundation (BHF)RG/11/7/28916RI CARDIOVASCULAR & MEDICAL SCIENCES