title: Endothelium-dependent mechanisms of the vasodilatory effect of the endocannabinoid, anandamide, in the rat pulmonary artery.
abstract: Endocannabinoids exhibit vasodilatory properties and reduce blood pressure in vivo. However, the influence and mechanism of action of the prominent endocannabinoid, anandamide (AEA), in pulmonary arteries are not known. The present study determined the vascular response to AEA in isolated rat pulmonary arteries. AEA relaxed rat pulmonary arteries that were pre-constricted with U-46619. This relaxation was reduced by the following conditions:removal of the endothelium; in KCl pre-constricted preparations; in the presence of the potassium channel (K(Ca)) blockers, tetraethylammonium and the combination of charybdotoxin and apamin, and the prostacyclin receptor antagonist, RO1138452. Inhibitors of cyclooxygenase (indomethacin), nitric oxide (NO) synthase (N(G)-nitro-l-arginine methyl ester) and fatty acid amide hydrolase (URB597) alone or in combination diminished AEA-induced relaxation in endothelium-intact vessels. The remaining experiments were performed in the presence of URB597 to eliminate the influence of AEA metabolites. Antagonists of the endothelial cannabinoid receptor (CB(x)), O-1918 and cannabidiol, attenuated the AEA-induced response. Antagonists of CB(1), CB(2) and TRPV1 receptors, AM251, AM630 and capsazepine, respectively, did not modify the AEA-induced response. A reference activator of CB(x) receptors, abnormal cannabidiol, mimicked the receptor-mediated AEA effects. The present study demonstrated that AEA relaxed rat pulmonary arteries in an endothelium-dependent fashion via the activation of the O-1918-sensitive CB(x) receptor and/or prostacyclin-like vasoactive products of AEA. One or both of these mechanisms may involve K(Ca) or the NO pathway.
authors.affiliation: Zakład Fizjologii i Patofizjologii Doświadczalnej, Uniwersytet Medyczny w Białymstoku, ul. Mickiewicza 2A, 15-222 Białystok, Poland. mabar@umb.edu.pl
authors.forename: Marta
authors.initials: M
authors.lastname: Baranowska-Kuczko
authors.forename: Margaret R
authors.initials: MR
authors.lastname: MacLean
authors.forename: Hanna
authors.initials: H
authors.lastname: Kozłowska
authors.forename: Barbara
authors.initials: B
authors.lastname: Malinowska
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000840:Anisoles / Q000494:pharmacology; D001030:Apamin / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D001593:Benzyl Compounds / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D003510:Cyclohexanes / Q000494:pharmacology; D063388:Endocannabinoids / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011189:Potassium Chloride / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000378:metabolism; D044006:Receptors, Epoprostenol / Q000037:antagonists & inhibitors / Q000378:metabolism; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000581:Amidohydrolases; D000840:Anisoles; D001030:Apamin; D001095:Arachidonic Acids; D001549:Benzamides; D001593:Benzyl Compounds; D063387:Cannabinoid Receptor Antagonists; D002211:Capsaicin; D002219:Carbamates; D018999:Charybdotoxin; D003510:Cyclohexanes; D063388:Endocannabinoids; D007093:Imidazoles; D007211:Indoles; D007213:Indomethacin; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D026902:Potassium Channel Blockers; D011189:Potassium Chloride; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D044006:Receptors, Epoprostenol; D050916:TRPV Cation Channels; D019789:Tetraethylammonium; D000099252:Fatty Acid Amide Hydrolases; C514222:(2-(4-(4-isopropoxybenzyl)-phenylamino) imidazoline); C552735:1,3-dimethoxy-5-methyl-2-(3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl)benzene; C494484:TRPV1 receptor; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C103505:AM 251; C071423:capsazepine; C094023:iodopravadoline; C078814:anandamide