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Anandamide-induced relaxation of sheep coronary arteries: the role of the vascular endothelium, arachidonic acid metabolites and potassium channels.

Abstract

1. The effects of the endocannabinoid, anandamide, and its metabolically stable analogue, methanandamide, on induced tone were examined in sheep coronary artery rings in vitro. 2. In endothelium-intact rings precontracted to the thromboxane A(2) mimetic, U46619, anandamide (0.01 - 30 microM) induced slowly developing concentration-dependent relaxations (pEC(50) [negative log of EC(50)]=6.1+/-0.1; R(max) [maximum response]=81+/-4%). Endothelium denudation caused a 10 fold rightward shift of the anandamide concentration-relaxation curve without modifying R(max). Methanandamide was without effect on U46619-induced tone. 3. The anandamide-induced relaxation was unaffected by the cannabinoid receptor antagonist, SR 141716A (3 microM), the vanilloid receptor antagonist, capsazepine (3 and 10 microM) or the nitric oxide synthase inhibitor, L-NAME (100 microM). 4. The cyclo-oxygenase inhibitor, indomethacin (3 and 10 microM) and the anandamide amidohydrolase inhibitor, PMSF (70 and 200 microM), markedly attenuated the anandamide response. The anandamide transport inhibitor, AM 404 (10 and 30 microM), shifted the anandamide concentration-response curve to the right. 5. Precontraction of endothelium-intact rings with 25 mM KCl attenuated the anandamide-induced relaxations (R(max)=7+/-7%), as did K(+) channel blockade with tetraethylammonium (TEA; 3 microM) or iberiotoxin (100 nM). Blockade of small conductance, Ca(2+)-activated K(+) channels, delayed rectifier K(+) channels, K(ATP) channels or inward rectifier K(+) channels was without effect. 6. These data suggest that the relaxant effects of anandamide in sheep coronary arteries are mediated in part via the endothelium and result from the cellular uptake and conversion of anandamide to a vasodilatory prostanoid. This, in turn, causes vasorelaxation, in part, by opening potassium channels.

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  • Authors+Show Affiliations

    ,

    Institute of Pharmacy and Chemistry, University of Sunderland, Dale Building, Sunderland SR1 3SD.

    Source

    British journal of pharmacology 134:5 2001 Nov pg 1003-12

    MeSH

    15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
    4-Aminopyridine
    Animals
    Apamin
    Arachidonic Acid
    Arachidonic Acids
    Barium
    Calcium Channel Blockers
    Cannabinoid Receptor Modulators
    Cannabinoids
    Capsaicin
    Coronary Vessels
    Cytochrome P-450 Enzyme Inhibitors
    Dose-Response Relationship, Drug
    Endocannabinoids
    Endothelium, Vascular
    Enzyme Inhibitors
    Fatty Acids, Unsaturated
    Glyburide
    In Vitro Techniques
    Indomethacin
    Miconazole
    NG-Nitroarginine Methyl Ester
    Nitric Oxide Synthase
    Peptides
    Phenylmethylsulfonyl Fluoride
    Piperidines
    Polyunsaturated Alkamides
    Potassium
    Potassium Channel Blockers
    Potassium Channels
    Pyrazoles
    Receptors, Drug
    Rimonabant
    Sheep
    Tetraethylammonium
    Vasoconstrictor Agents
    Vasodilation

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    11682448

    Citation

    Grainger, J, and G Boachie-Ansah. "Anandamide-induced Relaxation of Sheep Coronary Arteries: the Role of the Vascular Endothelium, Arachidonic Acid Metabolites and Potassium Channels." British Journal of Pharmacology, vol. 134, no. 5, 2001, pp. 1003-12.
    Grainger J, Boachie-Ansah G. Anandamide-induced relaxation of sheep coronary arteries: the role of the vascular endothelium, arachidonic acid metabolites and potassium channels. Br J Pharmacol. 2001;134(5):1003-12.
    Grainger, J., & Boachie-Ansah, G. (2001). Anandamide-induced relaxation of sheep coronary arteries: the role of the vascular endothelium, arachidonic acid metabolites and potassium channels. British Journal of Pharmacology, 134(5), pp. 1003-12.
    Grainger J, Boachie-Ansah G. Anandamide-induced Relaxation of Sheep Coronary Arteries: the Role of the Vascular Endothelium, Arachidonic Acid Metabolites and Potassium Channels. Br J Pharmacol. 2001;134(5):1003-12. PubMed PMID: 11682448.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Anandamide-induced relaxation of sheep coronary arteries: the role of the vascular endothelium, arachidonic acid metabolites and potassium channels. AU - Grainger,J, AU - Boachie-Ansah,G, PY - 2001/10/30/pubmed PY - 2002/1/5/medline PY - 2001/10/30/entrez SP - 1003 EP - 12 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 134 IS - 5 N2 - 1. The effects of the endocannabinoid, anandamide, and its metabolically stable analogue, methanandamide, on induced tone were examined in sheep coronary artery rings in vitro. 2. In endothelium-intact rings precontracted to the thromboxane A(2) mimetic, U46619, anandamide (0.01 - 30 microM) induced slowly developing concentration-dependent relaxations (pEC(50) [negative log of EC(50)]=6.1+/-0.1; R(max) [maximum response]=81+/-4%). Endothelium denudation caused a 10 fold rightward shift of the anandamide concentration-relaxation curve without modifying R(max). Methanandamide was without effect on U46619-induced tone. 3. The anandamide-induced relaxation was unaffected by the cannabinoid receptor antagonist, SR 141716A (3 microM), the vanilloid receptor antagonist, capsazepine (3 and 10 microM) or the nitric oxide synthase inhibitor, L-NAME (100 microM). 4. The cyclo-oxygenase inhibitor, indomethacin (3 and 10 microM) and the anandamide amidohydrolase inhibitor, PMSF (70 and 200 microM), markedly attenuated the anandamide response. The anandamide transport inhibitor, AM 404 (10 and 30 microM), shifted the anandamide concentration-response curve to the right. 5. Precontraction of endothelium-intact rings with 25 mM KCl attenuated the anandamide-induced relaxations (R(max)=7+/-7%), as did K(+) channel blockade with tetraethylammonium (TEA; 3 microM) or iberiotoxin (100 nM). Blockade of small conductance, Ca(2+)-activated K(+) channels, delayed rectifier K(+) channels, K(ATP) channels or inward rectifier K(+) channels was without effect. 6. These data suggest that the relaxant effects of anandamide in sheep coronary arteries are mediated in part via the endothelium and result from the cellular uptake and conversion of anandamide to a vasodilatory prostanoid. This, in turn, causes vasorelaxation, in part, by opening potassium channels. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/11682448/Anandamide_induced_relaxation_of_sheep_coronary_arteries:_the_role_of_the_vascular_endothelium_arachidonic_acid_metabolites_and_potassium_channels_ L2 - https://doi.org/10.1038/sj.bjp.0704340 DB - PRIME DP - Unbound Medicine ER -