title: Tongxinluo Induces nNOS Expression Through ERK Activation: Possible Contribution to the Effects of Tongxinluo to Attenuate Vasoconstriction.
abstract: OBJECTIVE
  Vasoconstriction and hypersensitivity to the vasoconstrictive action of serotonin occurs in the early stage of atherosclerosis. Vascular neural nitric oxide synthase (nNOS) plays an important role in the regulation of vascular tone and is vasoprotective against atherosclerosis. In this study, we intended to investigate the possible role of nNOS in mediating the effect of Chinese medicine Tongxinluo (TXL) to attenuate vasoconstriction induced by the chronic injury in the collared carotid artery.
  
  
  METHODS
  Twenty-four male Wistar Kyoto rats were assigned to 2 treatments (n = 12): vehicle and TXL (400 mg·kg·d). After 2 weeks of treatment, adventitia injury was induced by placing a silicone collar around the left carotid artery for 2 weeks. Blood flow and vascular reactivity to serotonin were determined, and carotid arteries were harvested for morphometry, RT-PCR, and Western blotting analysis. Expression of nNOS and phosphorylated ERK1/2 was also analyzed in primary cultured vascular smooth muscle cells after TXL and/or ERK kinase inhibitor treatment.
  
  
  RESULTS
  Adventitia injury induced by the placement of a silicone collar around the carotid artery for 2 weeks led to chronic vasoconstriction and vascular hypersensitivity to serotonin, which was attenuated by TXL treatment. TXL improved the carotid blood flow and normalized the vascular hypersensitivity to serotonin in collared carotid arteries. The expression of nNOS and phosphorylated ERK1/2 was increased by TXL treatment in both collared carotid artery and vascular smooth muscle cells indicating a possible contribution of ERK1/2 and nNOS signaling to the beneficial effects of TXL. Moreover, we showed that the effect of TXL to increase nNOS expression was mediated by the phosphorylated ERK1/2 since the effect could be abolished by the ERK kinase inhibitor PD98059.
  
  
  CONCLUSIONS
  TXL increases nNOS expression in the collared carotid artery through activation of ERK1/2 signaling, which may have contributed to the attenuation of vasoconstriction induced by the collar-induced adventitia injury.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Qigang
authors.initials: Q
authors.lastname: Guan
authors.forename: Moujie
authors.initials: M
authors.lastname: Liu
authors.forename: Rihui
authors.initials: R
authors.lastname: Liu
authors.forename: Haishan
authors.initials: H
authors.lastname: Zhang
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Pang
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Sun
authors.forename: Dingyin
authors.initials: D
authors.lastname: Zeng
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis*; D051381:Rats; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D004365:Drugs, Chinese Herbal; C513941:tongxinluo; D052248:Nitric Oxide Synthase Type I