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

Abstract

BACKGROUND AND PURPOSE

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.

EXPERIMENTAL APPROACH

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.

KEY RESULTS

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.

CONCLUSIONS AND IMPLICATIONS

These data suggest that endocannabinoids contribute to hyperdynamic circulation and mesenteric hyperaemia in cirrhosis, via CB(1)- and VR1-mediated mechanisms.

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  • Authors+Show Affiliations

    ,

    Liver Unit, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.

    , , , ,

    Source

    British journal of pharmacology 149:7 2006 Dec pg 898-908

    MeSH

    Animals
    Arachidonic Acids
    Bile Ducts
    Blood Flow Velocity
    Blood Pressure
    Blotting, Western
    Capsaicin
    Cardiac Output
    Disease Models, Animal
    Endocannabinoids
    Hyperemia
    Indoles
    Liver Circulation
    Liver Cirrhosis, Biliary
    Male
    Mesenteric Artery, Superior
    Piperidines
    Polyunsaturated Alkamides
    Pyrazoles
    RNA, Messenger
    Rats
    Rats, Sprague-Dawley
    Receptor, Cannabinoid, CB1
    Receptor, Cannabinoid, CB2
    Reverse Transcriptase Polymerase Chain Reaction
    Splanchnic Circulation
    TRPV Cation Channels
    Time Factors
    Vascular Resistance
    Vasodilation
    Vasodilator Agents

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    17043671

    Citation

    Moezi, L, et al. "Anandamide Mediates Hyperdynamic Circulation in Cirrhotic Rats Via CB(1) and VR(1) Receptors." British Journal of Pharmacology, vol. 149, no. 7, 2006, pp. 898-908.
    Moezi L, Gaskari SA, Liu H, et al. Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB(1) and VR(1) receptors. Br J Pharmacol. 2006;149(7):898-908.
    Moezi, L., Gaskari, S. A., Liu, H., Baik, S. K., Dehpour, A. R., & Lee, S. S. (2006). Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB(1) and VR(1) receptors. British Journal of Pharmacology, 149(7), pp. 898-908.
    Moezi L, et al. Anandamide Mediates Hyperdynamic Circulation in Cirrhotic Rats Via CB(1) and VR(1) Receptors. Br J Pharmacol. 2006;149(7):898-908. PubMed PMID: 17043671.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB(1) and VR(1) receptors. AU - Moezi,L, AU - Gaskari,S A, AU - Liu,H, AU - Baik,S K, AU - Dehpour,A R, AU - Lee,S S, Y1 - 2006/10/16/ PY - 2006/10/18/pubmed PY - 2007/2/3/medline PY - 2006/10/18/entrez SP - 898 EP - 908 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 149 IS - 7 N2 - BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: 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. CONCLUSIONS AND IMPLICATIONS: These data suggest that endocannabinoids contribute to hyperdynamic circulation and mesenteric hyperaemia in cirrhosis, via CB(1)- and VR1-mediated mechanisms. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/17043671/Anandamide_mediates_hyperdynamic_circulation_in_cirrhotic_rats_via_CB_1__and_VR_1__receptors_ L2 - https://doi.org/10.1038/sj.bjp.0706928 DB - PRIME DP - Unbound Medicine ER -