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PMID: 17043671 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB(1) and VR(1) receptors.

British journal of pharmacology ·Vol. 149 ·No. 7 ·2006-12-00 ·Pages 898-908

Moezi L, Gaskari SA, Liu H, Baik SK, Dehpour AR, Lee SS

Abstract

Hyperdynamic circulation and mesenteric hyperaemia are found in cirrhosis. To delineate the role of endocannabinoids in these changes, we examined the cardiovascular effects of anandamide, AM251 (CB(1) antagonist), AM630 (CB(2) antagonist) and capsazepine (VR1 antagonist), in a rat model of cirrhosis. Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, diameters of mesenteric arteriole and venule (intravital microscopy), arterial pressure, cardiac output, systemic vascular resistance and superior mesenteric artery (SMA) flow were measured after anandamide, AM251 (with or without anandamide), AM630 and capsazepine administration. CB(1), CB(2) and VR1 receptor expression in SMA was assessed by western blot and RT-PCR. Anandamide increased mesenteric vessel diameter and flow, and cardiac output in cirrhotic rats, but did not affect controls. Anandamide induced a triphasic arterial pressure response in controls, but this pattern differed markedly in cirrhotic rats. Pre-administration of AM251 blocked the effects of anandamide. AM251 (without anandamide) increased arterial pressure and systemic vascular resistance, constricted mesenteric arterioles, decreased SMA flow and changed cardiac output in a time-dependent fashion in cirrhotic rats. Capsazepine decreased cardiac output and mesenteric arteriolar diameter and flow, and increased systemic vascular resistance in cirrhotic rats, but lacked effect in controls. Expression of CB(1) and VR1 receptor proteins were increased in cirrhotic rats. AM630 did not affect any cardiovascular parameter in either group. These data suggest that endocannabinoids contribute to hyperdynamic circulation and mesenteric hyperaemia in cirrhosis, via CB(1)- and VR1-mediated mechanisms.

MeSH Terms
Animals Arachidonic Acids/pharmacology Bile Ducts/surgery Blood Flow Velocity Blood Pressure/drug effects Blotting, Western Capsaicin/analogs & derivatives,pharmacology Cardiac Output/drug effects Disease Models, Animal Endocannabinoids Hyperemia/etiology,metabolism,physiopathology Indoles/pharmacology Liver Circulation/drug effects Liver Cirrhosis, Biliary/complications,metabolism,physiopathology Male Mesenteric Artery, Superior/chemistry,drug effects Piperidines/pharmacology Polyunsaturated Alkamides/pharmacology Pyrazoles/pharmacology RNA, Messenger/analysis Rats Rats, Sprague-Dawley Receptor, Cannabinoid, CB1/analysis,drug effects,metabolism Receptor, Cannabinoid, CB2/drug effects Reverse Transcriptase Polymerase Chain Reaction Splanchnic Circulation/drug effects TRPV Cation Channels/analysis,drug effects,metabolism Time Factors Vascular Resistance/drug effects Vasodilation/drug effects Vasodilator Agents/pharmacology
Chemicals
Arachidonic Acids Endocannabinoids Indoles Piperidines Polyunsaturated Alkamides Pyrazoles RNA, Messenger Receptor, Cannabinoid, CB1 Receptor, Cannabinoid, CB2 TRPV Cation Channels TRPV1 receptor Vasodilator Agents AM 251 capsazepine Capsaicin iodopravadoline anandamide
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Moezi L
Liver Unit, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Gaskari S A
Liu H
Baik S K
Dehpour A R
Lee S S
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1038/sj.bjp.0706928
Published
2006-12-00
Epub
2006-00-16
Pages
898-908
Language
English
Region
England
NLM ID
7502536
PMCID
PMC2014695
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjp.0706928 PMC Full Text View journal details
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