title: Luteolin reduces high glucose-mediated impairment of endothelium-dependent relaxation in rat aorta by reducing oxidative stress.
abstract: While luteolin, a flavone rich in many plants, has some cardiovascular activity, it is not clear whether luteolin has beneficial effects on the vascular endothelial impairment in hyperglycemia/high glucose. Here, we reveal the protective effect of luteolin on endothelium-dependent relaxation in isolated rat aortic rings exposed to high glucose. The thoracic aorta of male Sprague-Dawley rats was rapidly dissected out and the effect of luteolin on the tension of aortic rings pretreated with high glucose (44mM) for 4h was measured in an organ bath system. The levels of nitric oxide (NO), hydroxy radical (OH(-)) and reactive oxygen species (ROS), and the activity of superoxide dismutase (SOD) and nitric oxide synthase (NOS) were measured in aortas. The vasorelaxation after treatment with luteolin for 8 weeks in aortic rings from diabetic rats was also determined. We found that exposure to high glucose decreased acetylcholine-induced endothelium-dependent relaxation. However, high mannitol had no effect on vasorelaxation. Luteolin evoked a concentration-dependent relaxation in aortic rings previously contracted by phenylephrine, and the pD(2) value was 5.24+/-0.04. The EC(50) of luteolin markedly attenuated the inhibition of relaxation induced by high glucose, which was significantly weakened by pretreatment with l-NAME (0.1mM), but not by indomethacin (0.01mM). Luteolin significantly inhibited the increase of ROS level and OH(-) formation, and the decrease of NO level, NOS and SOD activity caused by high glucose. The improving effect of luteolin on endothelium-dependent vasorelaxation in diabetic rat aortic rings was reversed by pretreatment with l-NAME or methylene blue. The results indicate that the decrease of endothelium-dependent relaxation in rat aortic rings exposed to high glucose is markedly attenuated by luteolin, which may be mediated by reducing oxidative stress and enhancing activity in the NOS-NO pathway.
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, 388 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Ling-Bo
authors.initials: LB
authors.lastname: Qian
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Fang-Xia
authors.initials: FX
authors.lastname: Chen
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Ma
authors.forename: Iain C
authors.initials: IC
authors.lastname: Bruce
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D066298:In Vitro Techniques; D047311:Luteolin / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D005947:Glucose; D047311:Luteolin