title: Endothelial CB1-receptors limit infarct size through NO formation in rat isolated hearts.
abstract: The aim of the present study was to document the presence of cannabinoid receptors in the rat heart, and to assess the cardioprotective properties of CB(1)- and CB(2)-receptor agonists. Rat isolated hearts were exposed to low-flow ischemia and reperfusion, with selective cannabinoid agonists administered prior to and during the ischemic period. In some hearts, RT-PCR, Western blots, and immunohistological techniques were used to identify and localize both cannabinoid-receptor subtypes. The effect of cannabinoids on infarct size was evaluated in additional hearts using TTC staining. Protein and mRNA for both CB(1)- and CB(2)-receptors were found in rat heart extracts. CB(1)-receptors were localized almost exclusively on arterial and capillary endothelial cells in intact hearts, whereas CB(2)-receptors appeared on cardiomyocytes and endothelial cells of larger arteries. Both the CB(1)-agonist, ACEA (50 nM), and the CB(2)-agonist, JWH015 (50 nM), reduced infarct size. However, only the cardioprotective effect of the CB(1)-agonist was blocked by the NO-synthase inhibitor, N(G)-nitro-L-arginine (30 microM). In conclusion, CB(1)-receptors are present mainly on endothelial cells in the rat heart, and exert their effect through production of NO. In contrast, CB(2)-receptors present on cardiomyocytes exert a cardioprotective effect independent of this endothelial factor.
authors.affiliation: Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, QC, Canada H3C 3J7.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lépicier
authors.forename: Caroline
authors.initials: C
authors.lastname: Lagneux
authors.forename: Martin G
authors.initials: MG
authors.lastname: Sirois
authors.forename: Daniel
authors.initials: D
authors.lastname: Lamontagne
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D015153:Blotting, Western; D004727:Endothelium / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000502:physiology*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001095:Arachidonic Acids; D007211:Indoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C119325:arachidonyl-2-chloroethylamide; D009569:Nitric Oxide; D012313:RNA; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C402944:JHW 015