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Mechanisms of anandamide-induced vasorelaxation in rat isolated coronary arteries.
Br J Pharmacol. 2001 Oct; 134(4):921-9.BJ

Abstract

1. The cannabinoid arachidonyl ethanolamide (anandamide) caused concentration-dependent relaxation of 5-HT-precontracted, myograph-mounted, segments of rat left anterior descending coronary artery. 2. This relaxation was endothelium-independent, unaffected by the fatty acid amide hydrolase inhibitor, arachidonyl trifluoromethyl ketone (10 microM), and mimicked by the non-hydrolysable anandamide derivative, methanandamide. 3. Relaxations to anandamide were attenuated by the cannabinoid receptor antagonist, SR 141716A (3 microM), but unaffected by AM 251 (1 microM) and AM 630 (1 microM), more selective antagonists of cannabinoid CB(1) and CB(2) receptors respectively. Palmitoylethanolamide, a selective CB(2) receptor agonist, did not relax precontracted coronary arteries. 4. Anandamide relaxations were not affected by inhibition of sensory nerve transmission with capsaicin (10 microM) or blockade of vanilloid VR1 receptors with capsazepine (5 microM). Nevertheless capsaicin relaxed coronary arteries in a concentration-dependent and capsazepine-sensitive manner, confirming functional sensory nerves were present. In contrast, capsazepine and capsaicin did inhibit anandamide relaxations in methoxamine-precontracted rat small mesenteric arteries. 5. Relaxations to anandamide were inhibited by TEA (1 mM) or iberiotoxin (50 nM), blockers of large conductance, Ca(2+)-activated K(+) channels (BK(Ca)). Gap junction inhibition with 18alpha-glycyrrhetinic acid (100 microM) did not affect anandamide relaxations. 6. This study shows anandamide relaxes the rat coronary artery by a novel mechanism. Anandamide-induced relaxations do not involve the endothelium, degradation into active metabolites, or activation of cannabinoid CB(1) or CB(2) receptors, but may involve activation of BK(Ca). Vanilloid receptor activation also has no role in the effects of anandamide in coronary arteries, even though functional sensory nerves are present.

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Authors+Show Affiliations

White R
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QJ.
Ho WS
No affiliation info available
Bottrill FE
No affiliation info available
Ford WR
No affiliation info available
Hiley CR
No affiliation info available

MeSH

AmidesAnimalsArachidonic AcidsCapsaicinCoronary VesselsDose-Response Relationship, DrugEndocannabinoidsEndothelium, VascularEthanolaminesGap JunctionsGlycyrrhetinic AcidIn Vitro TechniquesIndolesIndomethacinMalePalmitic AcidsPeptidesPiperidinesPolyunsaturated AlkamidesPotassium Channel BlockersPyrazolesRatsRats, WistarReceptor, Cannabinoid, CB2Receptors, CannabinoidReceptors, DrugRimonabantSerotoninTetraethylammoniumVasodilation

Pub Type(s)

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

Language

eng

PubMed ID

11606334

Citation

White, R, et al. "Mechanisms of Anandamide-induced Vasorelaxation in Rat Isolated Coronary Arteries." British Journal of Pharmacology, vol. 134, no. 4, 2001, pp. 921-9.
White R, Ho WS, Bottrill FE, et al. Mechanisms of anandamide-induced vasorelaxation in rat isolated coronary arteries. Br J Pharmacol. 2001;134(4):921-9.
White, R., Ho, W. S., Bottrill, F. E., Ford, W. R., & Hiley, C. R. (2001). Mechanisms of anandamide-induced vasorelaxation in rat isolated coronary arteries. British Journal of Pharmacology, 134(4), 921-9.
White R, et al. Mechanisms of Anandamide-induced Vasorelaxation in Rat Isolated Coronary Arteries. Br J Pharmacol. 2001;134(4):921-9. PubMed PMID: 11606334.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms of anandamide-induced vasorelaxation in rat isolated coronary arteries. AU - White,R, AU - Ho,W S, AU - Bottrill,F E, AU - Ford,W R, AU - Hiley,C R, PY - 2001/10/19/pubmed PY - 2002/1/5/medline PY - 2001/10/19/entrez SP - 921 EP - 9 JF - British journal of pharmacology JO - Br J Pharmacol VL - 134 IS - 4 N2 - 1. The cannabinoid arachidonyl ethanolamide (anandamide) caused concentration-dependent relaxation of 5-HT-precontracted, myograph-mounted, segments of rat left anterior descending coronary artery. 2. This relaxation was endothelium-independent, unaffected by the fatty acid amide hydrolase inhibitor, arachidonyl trifluoromethyl ketone (10 microM), and mimicked by the non-hydrolysable anandamide derivative, methanandamide. 3. Relaxations to anandamide were attenuated by the cannabinoid receptor antagonist, SR 141716A (3 microM), but unaffected by AM 251 (1 microM) and AM 630 (1 microM), more selective antagonists of cannabinoid CB(1) and CB(2) receptors respectively. Palmitoylethanolamide, a selective CB(2) receptor agonist, did not relax precontracted coronary arteries. 4. Anandamide relaxations were not affected by inhibition of sensory nerve transmission with capsaicin (10 microM) or blockade of vanilloid VR1 receptors with capsazepine (5 microM). Nevertheless capsaicin relaxed coronary arteries in a concentration-dependent and capsazepine-sensitive manner, confirming functional sensory nerves were present. In contrast, capsazepine and capsaicin did inhibit anandamide relaxations in methoxamine-precontracted rat small mesenteric arteries. 5. Relaxations to anandamide were inhibited by TEA (1 mM) or iberiotoxin (50 nM), blockers of large conductance, Ca(2+)-activated K(+) channels (BK(Ca)). Gap junction inhibition with 18alpha-glycyrrhetinic acid (100 microM) did not affect anandamide relaxations. 6. This study shows anandamide relaxes the rat coronary artery by a novel mechanism. Anandamide-induced relaxations do not involve the endothelium, degradation into active metabolites, or activation of cannabinoid CB(1) or CB(2) receptors, but may involve activation of BK(Ca). Vanilloid receptor activation also has no role in the effects of anandamide in coronary arteries, even though functional sensory nerves are present. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/11606334/Mechanisms_of_anandamide_induced_vasorelaxation_in_rat_isolated_coronary_arteries_ L2 - https://doi.org/10.1038/sj.bjp.0704333 DB - PRIME DP - Unbound Medicine ER -