title: Transgenic overexpression of uncoupling protein 2 attenuates salt-induced vascular dysfunction by inhibition of oxidative stress.
abstract: BACKGROUND
  Ablation of uncoupling protein 2 (UCP2) has been involved in the enhancement of salt sensitivity associated with increased superoxide level and decreased nitric oxide (NO) bioavailability. However, the role of overexpression of UCP2 in salt-induced vascular dysfunction remains elusive.
  
  
  METHODS
  UCP2 transgenic (TG) and wild-type (WT) mice were placed on either a normal-salt (NS, 0.5%) or a high-salt (HS, 8%) diet for 12 weeks. Blood pressure (BP) and hypotensive responses were measured, and the vascular tone, superoxide level, and NO bioavailability in aortas were measured in each group.
  
  
  RESULTS
  The TG mice had increased expression and function of UCP2 in vascular smooth muscle cells. The acetylcholine (ACh)- and nitroglycerin (NTG)-induced hypotensive responses and aortic relaxations were significantly blunted in WT mice fed with an HS diet compared with an NS diet. These harmful effects were prevented in UCP2 TG mice. The impairments of ACh- and NTG-induced relaxation in aorta were inhibited by the endothelial NO synthase (eNOS) inhibitor L-NAME and mitochondrial antioxidant MitoQ, respectively. The HS intake led to a significant increase in superoxide production and a comparable decrease in NO bioavailability in aortas, and these effects were blunted in UCP2 TG mice. The expression of UCP2 was slightly increased in the HS group. However, the expression and phosphorylation of eNOS were not affected by an HS diet and overexpression of UCP2.
  
  
  CONCLUSIONS
  These findings suggest that overexpression of UCP2 can ameliorate salt-induced vascular dysfunction. This beneficial effect of UCP2 is mediated by decreased superoxide and reserved NO bioavailability.
authors.affiliation: Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan, PR China.
authors.forename: Shuangtao
authors.initials: S
authors.lastname: Ma
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dachun
authors.initials: D
authors.lastname: Yang
authors.forename: De
authors.initials: D
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Tang
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress; D017673:Sodium Chloride, Dietary; D013481:Superoxides / Q000378:metabolism; D000071246:Uncoupling Protein 2; D015854:Up-Regulation; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017673:Sodium Chloride, Dietary; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D014665:Vasodilator Agents; D013481:Superoxides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
keywords: blood pressure; high salt intake; hypertension; hypotensive response; nitric oxide; superoxide; uncoupling protein 2; vascular dysfunction.