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Articles in PresS, published online ahead of print January 24, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00497.2001
Submitted on June 6, 2001
Accepted on January 8, 2002
1 Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, MO, USA; Program in Neuroscience, Drug Abuse Research, J.L. Chambers Biomedical, Biotechnology Research Institute, North Carolina Central University, Durham, NC, USA
2 Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, MO, USA
3 Program in Neuroscience, Drug Abuse Research, J.L. Chambers Biomedical, Biotechnology Research Institute, North Carolina Central University, Durham, NC, USA
The endogenous cannabinoid, anandamide (arachidonylethanolamide), produces vasorelaxation in different vascular beds. In the present study, we have found that anandamide and the metabolically stable analog, methanandamide, produced dosedependent (10 nM - 10 µM) vasorelaxation of about 80% in the rabbit aortic ring preparation in an endothelium-dependent manner. Non-endothelium-dependent vasorelaxation was observed to be a maximum of 20-22% at > 10 µM methanandamide. The efficacious CB1 receptor analogs desacetyllevonantradol (10 µM) and WIN55212-2 (10 µM) failed to produce vasorelaxation; however, vasorelaxation was partially (75%)blocked by the CB1 receptor antagonist SR141716A. The VR1 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 othelium-denuded preparations. Pretreatment of the aortic rings with NG Nitro-L-Arginine methyl ester ompletely blocked the methanandamide-, capsaicin-, and CGRP- induced orelaxation. Pretreatment of aortic rings with pertussis toxin attenuated the methanandamide-induced vasorelaxation in endothelium-intact aortic rings, indicating the involvement of Gi/o-proteins in the vasorelaxation; however, pertussis toxin treatment failed to block the endotheliumindependent response. Thus, in rabbit aorta, methanandamide-induced vasorelaxation exhibits two components: 1) in endothelium-intact rings, an SR141716A-sensitive, non- CB1 receptor component that requires pertussis toxin-sensitive G proteins and NO production; and 2) in endothelium-denuded rings, a component that is mediated by VR1 vanilloid receptors and possibly by the subsequent release of CGRP, that requires NO production but is independent of pertussis toxin-sensitive G proteins.
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