title: Arecoline improves vascular endothelial function in high fructose-fed rats via increasing cystathionine-γ-lyase expression and activating K(ATP) channels.
abstract: OBJECTIVE
  To investigate the effect of arecoline, a major component of betel nut, on vascular endothelial function in high fructose-fed rats and the potential mechanisms underlying the effect.
  
  
  METHODS
  Male Wistar rats were fed a high-fructose or control diet for 16 weeks. At the beginning of week 13, the rats were injected ip with low (0.5 mg·kg(-1)·d(-1)), medium (1.0 mg·kg(-1)·d(-1)) or high (5.0 mg·kg(-1)·d(-1)) doses of arecoline for 4 weeks. At the termination of the treatments, blood was collected, fasting blood glucose (FBG) and serum insulin (FSI) levels were measured, and insulin sensitivity index (ISI) was calculated. The thoracic aortas were isolated and aortic rings were prepared for studying ACh-induced endothelium-dependent vasorelaxation (EDVR). The mRNA and protein expression of cystathionine-γ-lyase (CSE) in the thoracic aortas was analyzed using RT-PCR and Western blot analysis, respectively.
  
  
  RESULTS
  In high fructose-fed rats, the levels of FBG and FSI were remarkably increased, whereas the ISI and the mRNA and protein expression of CSE were significantly decreased. ACh-induced EDVR in the aortic rings from high fructose-fed rats was remarkably reduced. These changes were reversed by treatment with high dose arecoline. Pretreatment of the aortic rings rings from high fructose-fed rats with the CSE inhibitor propargylglycine (10 mmol/L) or the ATP-sensitive potassium (K(ATP)) channel blocker glibenclamide (10 mmol/L) abolished the restoration of ACh-induced EDVR by high dose arecoline. On the contrary, treatment with high dose arecoline significantly impaired ACh-induced EDVR in the aortic rings from control rats, and pretreatment with propargylglycine or glibenclamide did not cause further changes.
  
  
  CONCLUSIONS
  Arecoline treatment improves ACh-induced EDVR in high fructose-fed rats, and the potential mechanism of action might be associated with increase of CSE expression and activation of K(ATP) channels by arecoline.
authors: Department of Physiology, College of Medicine, University of South China, Hengyang 421001, China.
authors: Hong-yan
authors: HY
authors: Ling
authors: Guang
authors: G
authors: Wang
authors: Wei
authors: W
authors: Zhang
authors: Xing
authors: X
authors: Li
authors: Shou-hong
authors: SH
authors: Zhou
authors: Bi
authors: B
authors: Hu
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology; D001115:Arecoline / Q000494:pharmacology*; D003542:Cystathionine gamma-Lyase / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D005632:Fructose / Q000008:administration & dosage / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar
chemical_list: D054086:KATP Channels; D005632:Fructose; D001115:Arecoline; D003542:Cystathionine gamma-Lyase