title: Effect of tongxinluo on vasoconstriction induced by the chronic injury of the adventitia in the rat carotid artery.
abstract: OBJECTIVE
  Tongxinluo (TXL) is a traditional Chinese medicine that is developed on the meridian theory of traditional Chinese medicine, with the function of alleviating the angina. The present study was undertaken to explore the molecular mechanism of TXL in treating the pectoris angina through observing the effectiveness of TXL superfine powder on the vasoconstriction and the activation of RhoA/Rho-kinase pathway induced by the injury of the adventitia.
  
  
  METHODS
  36 male Wistar Kyoto rats were assigned to 3 treatments (n=12): vehicle, TXL (400 mg kg(-1) day(-1)) and fasudil (15 mg kg(-1) day(-1)). After 1 week of treatment, adventitia injury was induced by positioning a silicone collar around the right carotid artery for 1 week. Blood flow and vascular reactivity to serotonin were determined 1 week after injurying, the both sides of carotids were harvested for morphometry, Western blotting analysis and RT-PCR analysis.
  
  
  RESULTS
  Adventitia injury leaded to histological changes of vasoconstriction with the lumen cross-sectional area of 44.7% (p<0.001) decreasing and the media diameter of 62.31% (p<0.001) increasing, accompanying by the reduction of the blood flow and the increase of vascular reactivity sensitivity to serotonin. Treatment with both TXL superfine powder and fasudil can prevent the development of vasoconstriction, improve the carotid blood flow and normalize the vascular hypersensitivity to serotonin. Adventitia injuring of the rat carotid increased the expression of Rho-kinase mRNA and p-MYPT1(Thr696) protein by 1.78-fold (p<0.05) and >2-fold respectively (p<0.05). TXL reduced the expression of Rho-kinase mRNA and p-MYPT1(Thr696) protein by 54.2% (p<0.05) and 57.1% (p<0.05) respectively in collared arteries. Fasudil restrained the p-MYPT1(Thr696) protein expression by 63.8% (p<0.05) in collared arteries, did not affect the collar-induced the increase of Rho-kinase mRNA expression (p>0.05).
  
  
  CONCLUSIONS
  Treatment with TXL, similar to that with fasudil, can effectively prevent collar-induced vasoconstriction and vascular hyperreactivity to serotonin through inhibiting the RhoA/Rho-kinase pathway.
authors.affiliation: Cardiology Department, The First Affiliated Hospital of China Medical University, Heping District, Shenyang, China.
authors.forename: Lian Na
authors.initials: LN
authors.lastname: Xie
authors.forename: Ding Yin
authors.initials: DY
authors.lastname: Zeng
authors.forename: Hai Shan
authors.initials: HS
authors.lastname: Zhang
authors.forename: Dan Meng
authors.initials: DM
authors.lastname: Sun
authors.forename: Xue Feng
authors.initials: XF
authors.lastname: Pang
authors.forename: Qi Gang
authors.initials: QG
authors.lastname: Guan
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003238:Connective Tissue / Q000293:injuries; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D018056:Hemorheology / Q000187:drug effects; D008297:Male; D008517:Phytotherapy; D011208:Powders; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D011208:Powders; D012333:RNA, Messenger; D014665:Vasodilator Agents; C513941:tongxinluo; D012701:Serotonin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1; D020742:rhoA GTP-Binding Protein; C049347:fasudil