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Characterization of vasorelaxant responses to anandamide in the rat mesenteric arterial bed.
J Physiol. 2002 Mar 15; 539(Pt 3):893-902.JP

Abstract

The endogenous cannabinoid anandamide has recently been identified as a vasorelaxant but the underlying mechanisms are controversial. The vasorelaxant responses to anandamide have now been examined in the rat mesenteric arterial bed. Anandamide caused potent vasorelaxations (pD(2) = 6.24 +/- 0.06; R(max) = 89.4 +/- 2.2 %) which were unaffected by inhibition of nitric oxide synthase with N(G)-nitro-L-arginine methyl ester (L-NAME; 300 microM). The responses were also predominantly endothelium independent and were unaffected by the cannabinoid CB(1) receptor antagonist SR141716A (1 microM), although at higher concentrations (3 and 10 microM) SR141716A was inhibitory. Both 1 mM ouabain (pD(2) = 5.90 +/- 0.07; R(max) = 50.4 +/- 6.5 %) and 100 microM 18alpha-glycyrrhetinic acid (pD(2) = 6.04 +/- 0.14; R(max) = 40.9 +/- 5.8 %) opposed anandamide-induced vasorelaxation. However, the gap junction inhibitors carbenoxolone (100 microM) and palmitoleic acid (50 microM) did not affect vasorelaxation to anandamide. Relaxation to anandamide was significantly attenuated by both capsaicin pretreatment to deplete the sensory nerves of neurotransmitters (pD(2) = 5.86 +/- 0.18; R(max) = 56.3 +/- 5.2 %) and the vanilloid antagonist ruthenium red (10 microM; pD(2) = 5.64 +/- 0.09; R(max) = 33.7 +/- 3.9 %). However, these inhibitory effects were prevented by the additional presence of L-NAME, when the relaxation to anandamide was unaffected (pD(2) = 6.19 +/- 0.07; R(max) = 81.9 +/- 2.8 %). The inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, also prevented capsaicin from inhibiting the responses to anandamide. The results of this study point to anandamide acting via several mechanisms, which include the involvement of sensory nerves, but only in the presence of nitric oxide.

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Authors+Show Affiliations

Harris D
School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK.
McCulloch AI
No affiliation info available
Kendall DA
No affiliation info available
Randall MD
No affiliation info available

MeSH

AnimalsAnimals, NewbornArachidonic AcidsBiological FactorsCapsaicinDrug SynergismEndocannabinoidsEnzyme InhibitorsGap JunctionsIn Vitro TechniquesIndomethacinMaleMesenteric ArteriesNG-Nitroarginine Methyl EsterNitric Oxide SynthasePolyunsaturated AlkamidesRatsRats, WistarReceptors, CannabinoidReceptors, DrugRuthenium RedVasodilationVasodilator Agents

Pub Type(s)

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

Language

eng

PubMed ID

11897858

Citation

Harris, David, et al. "Characterization of Vasorelaxant Responses to Anandamide in the Rat Mesenteric Arterial Bed." The Journal of Physiology, vol. 539, no. Pt 3, 2002, pp. 893-902.
Harris D, McCulloch AI, Kendall DA, et al. Characterization of vasorelaxant responses to anandamide in the rat mesenteric arterial bed. J Physiol. 2002;539(Pt 3):893-902.
Harris, D., McCulloch, A. I., Kendall, D. A., & Randall, M. D. (2002). Characterization of vasorelaxant responses to anandamide in the rat mesenteric arterial bed. The Journal of Physiology, 539(Pt 3), 893-902.
Harris D, et al. Characterization of Vasorelaxant Responses to Anandamide in the Rat Mesenteric Arterial Bed. J Physiol. 2002 Mar 15;539(Pt 3):893-902. PubMed PMID: 11897858.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of vasorelaxant responses to anandamide in the rat mesenteric arterial bed. AU - Harris,David, AU - McCulloch,Audrey I, AU - Kendall,David A, AU - Randall,Michael D, PY - 2002/3/19/pubmed PY - 2002/6/21/medline PY - 2002/3/19/entrez SP - 893 EP - 902 JF - The Journal of physiology JO - J Physiol VL - 539 IS - Pt 3 N2 - The endogenous cannabinoid anandamide has recently been identified as a vasorelaxant but the underlying mechanisms are controversial. The vasorelaxant responses to anandamide have now been examined in the rat mesenteric arterial bed. Anandamide caused potent vasorelaxations (pD(2) = 6.24 +/- 0.06; R(max) = 89.4 +/- 2.2 %) which were unaffected by inhibition of nitric oxide synthase with N(G)-nitro-L-arginine methyl ester (L-NAME; 300 microM). The responses were also predominantly endothelium independent and were unaffected by the cannabinoid CB(1) receptor antagonist SR141716A (1 microM), although at higher concentrations (3 and 10 microM) SR141716A was inhibitory. Both 1 mM ouabain (pD(2) = 5.90 +/- 0.07; R(max) = 50.4 +/- 6.5 %) and 100 microM 18alpha-glycyrrhetinic acid (pD(2) = 6.04 +/- 0.14; R(max) = 40.9 +/- 5.8 %) opposed anandamide-induced vasorelaxation. However, the gap junction inhibitors carbenoxolone (100 microM) and palmitoleic acid (50 microM) did not affect vasorelaxation to anandamide. Relaxation to anandamide was significantly attenuated by both capsaicin pretreatment to deplete the sensory nerves of neurotransmitters (pD(2) = 5.86 +/- 0.18; R(max) = 56.3 +/- 5.2 %) and the vanilloid antagonist ruthenium red (10 microM; pD(2) = 5.64 +/- 0.09; R(max) = 33.7 +/- 3.9 %). However, these inhibitory effects were prevented by the additional presence of L-NAME, when the relaxation to anandamide was unaffected (pD(2) = 6.19 +/- 0.07; R(max) = 81.9 +/- 2.8 %). The inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, also prevented capsaicin from inhibiting the responses to anandamide. The results of this study point to anandamide acting via several mechanisms, which include the involvement of sensory nerves, but only in the presence of nitric oxide. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/11897858/Characterization_of_vasorelaxant_responses_to_anandamide_in_the_rat_mesenteric_arterial_bed_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3751&date=2002&volume=539&spage=893 DB - PRIME DP - Unbound Medicine ER -