Arecoline improves vascular endothelial function in high fructose-fed rats via increasing cystathionine-γ-lyase expression and activating KATP channels  

作　　者：Hong-yan LING Guang WANG Wei ZHANG Xing LI Shou-hong ZHOU Bi HU 

机构地区：[1]Department of Physiology,College of Medicine,University of South China,Hengyang 421001,China [2]Department of Physiology,College of Xiangnan,Chenzhou 423043,China

出　　处：《Acta Pharmacologica Sinica》2012年第8期1023-1029,共7页中国药理学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China （No 81000328）, the fifty-first batch of China Postdoctoral Science Foundation （No 2012M511384）, and the Fund of the Research Project of Department of Science and Technology of Hunan Province （No 2007TP4018）.

摘　　要：Aim： 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^-l·d^-1）, medium （1.0 mg·kg^-l·d^-1） or high （5.0 mg·kg^-l·d^-1） doses of arecoline for 4 weeks. At the termination of the treat-ments, 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-y-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 fruc-tose-fed rats with the CSE inhibitor propargylglycine （10 mmol/L） or the ATP-sensitive potassium （KATp） channel blocker glibenclamide （10 mmol/L） abolished the restoration of ACh-induced EDVR by high dose arecoline. On the contrary, treatment with high dose areco- line significantly impaired ACh-induced EDVR in the aortic rings from control rats, and pretreatment with propargylglycine or glibencl-amide did not cause further changes. Conclusion： 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 KATP channels by arecoline.Aim： 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^-l·d^-1）, medium （1.0 mg·kg^-l·d^-1） or high （5.0 mg·kg^-l·d^-1） doses of arecoline for 4 weeks. At the termination of the treat-ments, 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-y-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 fruc-tose-fed rats with the CSE inhibitor propargylglycine （10 mmol/L） or the ATP-sensitive potassium （KATp） channel blocker glibenclamide （10 mmol/L） abolished the restoration of ACh-induced EDVR by high dose arecoline. On the contrary, treatment with high dose areco- line significantly impaired ACh-induced EDVR in the aortic rings from control rats, and pretreatment with propargylglycine or glibencl-amide did not cause further changes. Conclusion： 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 KATP channels by arecoline.

关 键 词：ARECOLINE betel-quid chewing propargylglycine glibenclamide high fructose-fed rat endothelium-dependent vasorelaxation cystathionine-y-lyase KATP channel diabetes mellitus vascular endothelial dysfunction 

分 类 号：Q959.837[生物学—动物学] Q591.2