title: Induction of heme oxygenase-1 ameliorates vascular dysfunction in streptozotocin-induced type 2 diabetic rats.
abstract: OBJECTIVE
  To explore the effects of heme oxygenase-1 (HO-1) on vascular dysfunction in high fat diet streptozotocin-induced type 2 diabetic (T2D) rats.
  
  
  METHODS
  Rats received a high-fat diet followed by a low dose of streptozotocin (30 mg/kg) to induce T2D. T2D rats were treated with hemin (1, 5, or 25mg/kg) or carbon monoxide-releasing molecule-2 (CORM-2, 5 mg/kg) for 4 weeks. Isometric contractions of aortic rings were measured. The expression of cyclooxygenase-2 (COX-2) and activities of HO, SOD, and MDA were evaluated.
  
  
  RESULTS
  The fasting blood glucose, blood insulin levels, and IR index in T2D rats were higher than those in the control group, which were ameliorated by HO-1 inducer hemin. The antidiabetic effect was accompanied by enhanced HO activity. The vascular relaxation response to ACh was decreased in T2D rats, while treatment with hemin could prevent such decrease in vasorelaxation. An increase in COX-2 expression was found in the aortas of T2D rats. Treatment of T2D rats with COX-2 inhibitor NS398 restored ACh-induced vasodilation. COX-2 overexpression in T2D rats was inhibited by hemin. Hemin treatment also inhibited the decline of SOD activity and the increase of MDA content in the aorta of T2D rats. CORM-2, an agent which releases the HO-1 product CO, could mimic the beneficial effect of hemin.
  
  
  CONCLUSIONS
  Induction of HO-1 with hemin ameliorates the abnormality of endothelium-dependent vascular relaxation in T2D rats. A possible mechanism involves suppression of reactive oxygen species production and inhibition of COX-2 up-regulation induced by diabetes mellitus.
authors.affiliation: Department of Pathophysiology, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Department of Respiratory Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ying
authors.affiliation: Department of Pathophysiology, Zhejiang University, Hangzhou 310000, Zhejiang, China.
authors.forename: Ying-ying
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Zhejiang University, Hangzhou 310000, Zhejiang, China.
authors.forename: Yue-liang
authors.initials: YL
authors.lastname: Shen
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Pathophysiology, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Ke-ke
authors.initials: KK
authors.lastname: Jin
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. Electronic address: wzyxywlx@163.com.
authors.forename: Liang-xing
authors.initials: LX
authors.lastname: Wang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002248:Carbon Monoxide / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004790:Enzyme Induction; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006427:Hemin / Q000494:pharmacology; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013311:Streptozocin; D014664:Vasodilation
chemical_list: D017382:Reactive Oxygen Species; D013311:Streptozocin; D006427:Hemin; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D000111:Acetylcysteine
keywords: Cyclooxygenase-2; Heme oxygenase-1; Type 2 diabetes; Vasorelaxation