title: Cannabinoids alter endothelial function in the Zucker rat model of type 2 diabetes.
abstract: Circulating levels of anandamide are increased in diabetes, and cannabidiol ameliorates a number of pathologies associated with diabetes. The aim of the present study was to examine how exposure to anandamide or cannabidiol might affect endothelial dysfunction associated with Zucker Diabetic Fatty rats. Age-matched Zucker Diabetic Fatty and Zucker lean rats were killed by cervical dislocation and their arteries mounted on a myograph at 37 °C. Arteries were incubated for 2h with anandamide, cannabidiol or vehicle, contracted, and cumulative concentration-response curves to acetylcholine were constructed. Anandamide (10 µM, 2h) significantly improved the vasorelaxant responses to acetylcholine in aortae and femoral arteries from Zucker Diabetic Fatty rats but not Zucker lean rats. By contrast, anandamide (1 µM, 2h) significantly blunted acetylcholine-induced vasorelaxation in third-order mesenteric arteries (G3) from Zucker Diabetic Fatty rats. Cannabidiol incubation (10 µM, 2h) improved acetylcholine responses in the arteries of Zucker Diabetic Fatty rats (aorta and femoral) and Zucker lean (aorta, femoral and G3 mesenteric), and this effect was greater in the Zucker Diabetic Fatty rat. These studies suggest that increased circulating endocannabinoids may alter vascular function both positively and negatively in type 2 diabetes, and that part of the beneficial effect of cannabidiol in diabetes may be due to improved endothelium-dependent vasorelaxation.
authors.affiliation: Division of Vascular Medicine, School of Graduate Entry Medicine and Health, University of Nottingham, Royal Derby Hospital, Derby, DE22 3DT, UK. Electronic address: mzxcs@nottingham.ac.uk.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Stanley
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Wheal
authors.forename: Michael D
authors.initials: MD
authors.lastname: Randall
authors.forename: Saoirse E
authors.initials: SE
authors.lastname: O'Sullivan
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001095:Arachidonic Acids / Q000494:pharmacology*; D002185:Cannabidiol / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D002185:Cannabidiol; C078814:anandamide
keywords: Anandamide; Cannabidiol; Diabetes; Endocannabinoid; Endothelium; Vasorelaxation