title: Xiaokening stimulates endothelial nitric oxide release in diabetic rats.
abstract: BACKGROUND
  Diabetes mellitus induces microangiopathic changes that lead to endothelial dysfunction. This study investigated the effect of Xiaokening, a type of Chinese compound medicine, on the mesenteric arteriolar endothelial cell function of diabetic rats and its underlying mechanism.
  
  
  METHODS
  Diabetes mellitus was induced in rat models via intraperitoneal injection of 60 mg/kg streptozotocin and observed over three weeks. Mesenteric arterioles, which were isolated in a cannulated and pressurised state, were incubated with intravascular injections of 1, 3 or 5 g/L Xiaokening for 24, 48 or 72 hours. The effects of Xiaokening on the release of nitric oxide (NO) on the mesenteric arterioles were detected under shear stress of 1, 10 and 20 dyn/cm(2). Biochemical methods were used to determine the activities of superoxide dismutase (SOD) and xanthine oxidase (XO). The expressions of endothelial NO synthase (eNOS), SOD and XO in the mesenteric arterioles were assessed using Western blot.
  
  
  RESULTS
  Compared to normal rat arterioles, less NO was released in the mesenteric arterioles of diabetic rats. Xiaokening was found to have a concentration- and time-dependent effect on NO release; when the shear stress was increased, there was a gradual increase in the release of NO. Compared to normal arterioles, the expression of eNOS in the mesenteric arterioles of diabetic rats was lower. Incubation with Xiaokening increased SOD activity and expression, and decreased XO activity and expression in the mesenteric arterioles of the diabetic rats.
  
  
  CONCLUSIONS
  Xiaokening was able to significantly increase NO release and improve the endothelial function of mesenteric arterioles through antioxidative mechanisms.
authors.affiliation: Department of Pathology, Xuzhou Medical College, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Physiology, Xuzhou Medical College, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Xuzhou Medical College, China.
authors.forename: Qunli
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Physiology, Xuzhou Medical College, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Physiology, Xuzhou Medical College, China.
authors.forename: Changdong
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Pathology, Xuzhou Medical College, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology, Xuzhou Medical College, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D001160:Arterioles / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004365:Drugs, Chinese Herbal; C000612640:xiaokening; D009569:Nitric Oxide; D013311:Streptozocin; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D010100:Oxygen
keywords: Xiaokening; diabetes mellitus; endothelial cells; nitric oxide