title: Upregulation of caveolin-1 contributes to aggravated high-salt diet-induced endothelial dysfunction and hypertension in type 1 diabetic rats.
abstract: OBJECTIVE
  Endothelial dysfunction and hypertension is more common in individuals with diabetes than in the general population. This study was aimed to investigate the underlying mechanisms responsible for endothelial dysfunction of type 1 diabetic rats fed with high-salt diet.
  
  
  METHODS
  Type 1 diabetes (DM) was induced by intraperitoneal injection of streptozotocin (70 mg·kg(-1)). Normal or diabetic rats were randomly fed high-salt food (HS, 8% NaCl) or standard food (CON) for 6 weeks.
  
  
  RESULTS
  Both HS (143±10 mmHg) and DM+HS (169±11 mmHg) groups displayed significantly higher systolic blood pressure than those in the CON group (112±12 mmHg, P<0.01). DM+HS rats exhibited more pronounced impairment of vasorelaxation to acetylcholine and insulin compared with either DM or HS. Akt/endothelial nitric oxide synthase (eNOS) phosphorylation levels and nitric oxide (NO) concentration in DM+HS were significantly lower than in DM. The levels of caveolin-1 (cav-1) in DM+HS were significantly higher than that in DM and HS. Co-immunoprecipitation results showed increased interaction between cav-1 and eNOS in the DM+HS group. In the presence of cav-1 small interfering RNA (siRNA), eNOS phosphorylations in human umbilical vein endothelial cells (HUVEC) were significantly increased compared with control siRNA. Cav-1 was slightly but not significantly lower in HUVEC cultured with high glucose and high-salt buffer solution and pretreated with wortmannin or l-nitro-arginine methyl ester.
  
  
  CONCLUSIONS
  Impaired endothelial Akt activation and increased cav-1 expression and resultant decreased eNOS activation contributes to aggravated high-salt diet-induced endothelial dysfunction and hypertension in DM rats.
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an 710032, China; Department of Physiology, Renji College, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Xing
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Chunjuan
authors.initials: C
authors.lastname: Mi
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zhengrui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Ma
authors.affiliation: Experiment Teaching Center, Fourth Military Medical University, Xi'an 710032, China. Electronic address: hfzhang@fmmu.edu.cn.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an 710032, China. Electronic address: fgao@fmmu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000821:Animal Feed; D000818:Animals; D001794:Blood Pressure; D051242:Caveolin 1 / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary / Q000009:adverse effects; D013599:Systole; D015854:Up-Regulation; D014664:Vasodilation
chemical_list: C495537:Cav1 protein, rat; D051242:Caveolin 1; D034741:RNA, Small Interfering; D012982:Sodium, Dietary; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III
keywords: Caveolin-1; Diabetes; Endothelial dysfunction; Hypertension; eNOS