title: Plasma endothelin-1 and nitric oxide correlate with ligustrazine alleviation of pulmonary artery hypertension in patients of chronic cor pulmonale from high altitude plateau during acute exacerbation.
abstract: OBJECTIVE
  To explore the mechanisms involved in the ligustrazine alleviation of the pulmonary artery hypertension (PAH) in patients of chronic obstructive pulmonary disease (COPD) associated with chronic cor pulmonale (CCP) during exacerbation.
  
  
  METHODS
  Seventy patients of COPD and CCP with acute exacerbation were randomly and equally divided into control group and treatment group. The control group received standard treatment with antibiotics, antiasthmatic and expectorant medications, and oxygenation; and the ligustrazine treatment group received ligustrazine treatment (80 mg/d; i.v.; for 2 weeks) in addition to the standard treatment. Before and at the end of 2 week treatment, the clinic responses of the two regimens were evaluated, plasma levels of endothelin-1 (ET-1) and nitric oxide (NO) were determined; arterial oxygen partial pressure (PaO2, mean pulmonary arterial pressure (mPAP), outflow tract of right ventricle (RVOT), and internal diameter of right ventricle (RV) were measured.
  
  
  RESULTS
  Good clinic benefits were achieved in both the standard and ligustrazine regimens, plasma level of ET-1, values of mPAP, RV and RVOT decreased significantly, plasma level of NO and PaO2 values decreased (all P < 0.01 vs pre-treatment to all parameters). Compared with the control group, ligustrazine greatly enhanced the clinic efficacy from 77.1% to 97.1% (P < 0.05), and also resulted in more significant changes of all these parameters (P < 0.01 vs control group for all parameters). For both groups, the levels of plasma ET-1 were positively correlated with values of mPAP, RVOT, and RV (r = 0.710, 0.853, and 0.766, respectively, all P = 0.000), and negatively correlated with plasma NO and PaO2 (r = - 0.823, and - 0.752, respectively, all P = 0.000).
  
  
  CONCLUSIONS
  Ligustrazine is effective in treating pulmonary artery hypertension during acute exacerbation of COPD and CCP in patients from the plateau area. The observed changes in the plasma levels of NO and ET-1 in response to ligustrazine treatment suggest that ligustrazine may act through the selective effect on pulmonary blood vessels to enhance the synthesis and release of NO and suppress those of ET-1 from lung vascular endothelial cells, thus reducing pulmonary artery pressure and decreasing pulmonary arterial hypertension.
authors.forename: En-Zhi
authors.initials: EZ
authors.lastname: Feng
authors.forename: Sheng-Yue
authors.initials: SY
authors.lastname: Yang
authors.forename: Ning-Xia
authors.initials: NX
authors.lastname: Huang
authors.forename: He
authors.initials: H
authors.lastname: Yin
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhong-Xin
authors.initials: ZX
authors.lastname: Tian
mesh_terms: D000531:Altitude; D001784:Blood Gas Analysis; D002908:Chronic Disease; D019332:Endothelin-1 / Q000097:blood*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D009569:Nitric Oxide / Q000097:blood*; D011651:Pulmonary Artery / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D011719:Pyrazines / Q000627:therapeutic use*; D012119:Respiration
chemical_list: D019332:Endothelin-1; D011719:Pyrazines; D009569:Nitric Oxide; C017953:tetramethylpyrazine