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Anandamide-induced vasorelaxation in rabbit aortic rings has two components: G protein dependent and independent.
Am J Physiol Heart Circ Physiol. 2002 Jun; 282(6):H2046-54.AJ

Abstract

The endogenous cannabinoid anandamide (arachidonylethanolamide) produces vasorelaxation in different vascular beds. In the present study, we found that anandamide and a metabolically stable analog, methanandamide, produced dose-dependent (10 nM-10 microM) vasorelaxation of approximately 80% in a rabbit aortic ring preparation in an endothelium-dependent manner. Non-endothelium-dependent vasorelaxation was observed to be a maximum of 20-22% at >10 microM methanandamide. The efficacious CB(1) receptor analogs desacetyllevonantradol (10 microM) and WIN55212-2 (10 microM) failed to produce vasorelaxation; however, the endothelium-dependent vasorelaxation evoked by methanandamide was partially (75%) blocked by the CB(1) receptor antagonist SR141716A. The VR(1) vanilloid receptor antagonist capsazepine or the calcitonin gene-related peptide (CGRP) antagonist CGRP-(8-37) partially attenuated (25%) the vasorelaxation in endothelium-intact preparations and greatly reduced the response in endothelium-denuded preparations. Pretreatment of aortic rings with N(G)-nitro-L-arginine methyl ester completely blocked the methanandamide-, capsaicin-, and CGRP-induced vasorelaxation. Pretreatment of aortic rings with pertussis toxin attenuated the methanandamide-induced vasorelaxation in endothelium-intact aortic rings, indicating the involvement of G(i/o) proteins in the vasorelaxation; however, pertussis toxin treatment failed to block the endothelium-independent response. Thus, in the rabbit aorta, methanandamide-induced vasorelaxation exhibits two components: 1) in endothelium-intact rings, an SR141716A-sensitive, non-CB(1) receptor component that requires pertussis toxin-sensitive G proteins and nitric oxide (NO) production; and 2) in endothelium-denuded rings, a component that is mediated by VR(1) vanilloid receptors and possibly by the subsequent release of CGRP that requires NO production but is independent of pertussis toxin-sensitive G proteins.

Authors+Show Affiliations

Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA. smukhopadhyay@wpo.nccu.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12003810

Citation

Mukhopadhyay, Somnath, et al. "Anandamide-induced Vasorelaxation in Rabbit Aortic Rings Has Two Components: G Protein Dependent and Independent." American Journal of Physiology. Heart and Circulatory Physiology, vol. 282, no. 6, 2002, pp. H2046-54.
Mukhopadhyay S, Chapnick BM, Howlett AC. Anandamide-induced vasorelaxation in rabbit aortic rings has two components: G protein dependent and independent. Am J Physiol Heart Circ Physiol. 2002;282(6):H2046-54.
Mukhopadhyay, S., Chapnick, B. M., & Howlett, A. C. (2002). Anandamide-induced vasorelaxation in rabbit aortic rings has two components: G protein dependent and independent. American Journal of Physiology. Heart and Circulatory Physiology, 282(6), H2046-54.
Mukhopadhyay S, Chapnick BM, Howlett AC. Anandamide-induced Vasorelaxation in Rabbit Aortic Rings Has Two Components: G Protein Dependent and Independent. Am J Physiol Heart Circ Physiol. 2002;282(6):H2046-54. PubMed PMID: 12003810.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anandamide-induced vasorelaxation in rabbit aortic rings has two components: G protein dependent and independent. AU - Mukhopadhyay,Somnath, AU - Chapnick,Barry M, AU - Howlett,Allyn C, PY - 2002/5/11/pubmed PY - 2002/6/21/medline PY - 2002/5/11/entrez SP - H2046 EP - 54 JF - American journal of physiology. Heart and circulatory physiology JO - Am. J. Physiol. Heart Circ. Physiol. VL - 282 IS - 6 N2 - The endogenous cannabinoid anandamide (arachidonylethanolamide) produces vasorelaxation in different vascular beds. In the present study, we found that anandamide and a metabolically stable analog, methanandamide, produced dose-dependent (10 nM-10 microM) vasorelaxation of approximately 80% in a rabbit aortic ring preparation in an endothelium-dependent manner. Non-endothelium-dependent vasorelaxation was observed to be a maximum of 20-22% at >10 microM methanandamide. The efficacious CB(1) receptor analogs desacetyllevonantradol (10 microM) and WIN55212-2 (10 microM) failed to produce vasorelaxation; however, the endothelium-dependent vasorelaxation evoked by methanandamide was partially (75%) blocked by the CB(1) receptor antagonist SR141716A. The VR(1) vanilloid receptor antagonist capsazepine or the calcitonin gene-related peptide (CGRP) antagonist CGRP-(8-37) partially attenuated (25%) the vasorelaxation in endothelium-intact preparations and greatly reduced the response in endothelium-denuded preparations. Pretreatment of aortic rings with N(G)-nitro-L-arginine methyl ester completely blocked the methanandamide-, capsaicin-, and CGRP-induced vasorelaxation. Pretreatment of aortic rings with pertussis toxin attenuated the methanandamide-induced vasorelaxation in endothelium-intact aortic rings, indicating the involvement of G(i/o) proteins in the vasorelaxation; however, pertussis toxin treatment failed to block the endothelium-independent response. Thus, in the rabbit aorta, methanandamide-induced vasorelaxation exhibits two components: 1) in endothelium-intact rings, an SR141716A-sensitive, non-CB(1) receptor component that requires pertussis toxin-sensitive G proteins and nitric oxide (NO) production; and 2) in endothelium-denuded rings, a component that is mediated by VR(1) vanilloid receptors and possibly by the subsequent release of CGRP that requires NO production but is independent of pertussis toxin-sensitive G proteins. SN - 0363-6135 UR - https://www.unboundmedicine.com/medline/citation/12003810/Anandamide_induced_vasorelaxation_in_rabbit_aortic_rings_has_two_components:_G_protein_dependent_and_independent_ L2 - http://journals.physiology.org/doi/full/10.1152/ajpheart.00497.2001?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -