| Cytochrome P450 Pathway Contributes to Methanandamide-induced Vasorelaxation in Rat Aorta. | |
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MedLine Citation:
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PMID: 20814734 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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PURPOSE: The generation of hyperpolarising vasorelaxant endothelial cytochrome P450 epoxygenase (CYP)-derived metabolites of arachidonic may provide beneficial effects for the treatment of cardiovascular diseases in which the bioavailability of NO is impaired. The cannabinoid methanandamide has vasodilatory properties linked to hyperpolarisation. The aim of the present work was to investigate the vasorelaxant effects of methanandamide in rat aorta, focusing on the role of cytochrome P450 pathway. METHODS: Changes in isometric tension in response to a cumulative concentration-response curve of methanandamide (1 nM-100 μM) were recorded in aortic rings from male Wistar rats. The involvement of cannabinoid receptors, endothelial nitric oxide (NO)-, prostacyclin- and some hyperpolarising-mediated pathways were investigated. The activation of large-conductance Ca(2+)-activated K(+) (BKCa) channels have also been evaluated. RESULTS: Methanandamide provoked an endothelium-dependent vasorelaxation in rat aorta, reaching a maximal effect (Rmax) of 67% ± 2.6%. This vasorelaxation was clearly inhibited by the combination of CB(1) and CB(2) cannabinoid antagonists (Rmax: 21.6% ± 1.3%) and by the combination of guanylate cyclase and CYP inhibitors (Rmax: 16.7% ± 1.1%). The blockade induced separately by guanylate cyclase (31.3% ± 2.8%) or CYP (36.3% ± 6.6%) inhibitors on methanandamide vasorelaxation was not significantly modified by either CB(1) or CB(2) inhibition. BKCa channels inhibition caused a partial and significant inhibition of the methanandamide vasorelaxation (Rmax: 39.9% ± 3.3%). CONCLUSIONS: Methanandamide endothelium-dependent vasorelaxation is mediated by CB(1) and CB(2) cannabinoid receptors. The NO- and CYP-mediated pathways contribute in a concurrent manner in this vascular effect. Stimulation of both cannabinoid receptor subtypes is indistinctly linked to NO or CYP routes to cause vasorelaxation. |
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Authors:
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Visitación López-Miranda; M Teresa Dannert; Esperanza Herradón; Angela Alsasua; M Isabel Martín |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy Volume: 24 ISSN: 1573-7241 ISO Abbreviation: Cardiovasc Drugs Ther Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2011-03-09 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8712220 Medline TA: Cardiovasc Drugs Ther Country: United States |
Other Details:
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Languages: eng Pagination: 379-89 Citation Subset: IM |
Affiliation:
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Dpto. Farmacología y Nutrición, Facultad Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. Atenas s/n, 28922, Alcorcón, Madrid, Spain, visitacion.lopezmiranda@urjc.es. |
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