title: Anandamide-induced vasorelaxation in rabbit aortic rings has two components: G protein dependent and independent.
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: Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA. smukhopadhyay@wpo.nccu.edu
authors: Somnath
authors: S
authors: Mukhopadhyay
authors: Barry M
authors: BM
authors: Chapnick
authors: Allyn C
authors: AC
authors: Howlett
mesh_terms: D000818:Animals; D001011:Aorta; D001095:Arachidonic Acids / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D063388:Endocannabinoids; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D017629:Gap Junctions / Q000502:physiology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D037342:Pertussis Toxin; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D011817:Rabbits; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000502:physiology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000187:drug effects / Q000502:physiology; D000077285:Rimonabant; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D018015:Receptors, Calcitonin Gene-Related Peptide; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D010566:Virulence Factors, Bordetella; C088155:methanandamide; D019001:Nitric Oxide Synthase; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000077285:Rimonabant; D002211:Capsaicin; C078814:anandamide; D019331:NG-Nitroarginine Methyl Ester