title: Qiliqiangxin improves cardiac function in spontaneously hypertensive rats through the inhibition of cardiac chymase.
abstract: BACKGROUND
  This study was designed to investigate the effects and mechanism of action of the traditional Chinese drug formula, qiliqiangxin (QLQX), on cardiac function in spontaneously hypertensive rats (SHRs).
  
  
  METHODS
  We evaluated the effects of oral high-dose (4 g/kg/day, n = 7) and low-dose (1 g/kg/day, n = 7) QLQX on cardiac function in SHRs aged between 8 compared to control, the 8-week-old Wistar-Kyoto (WKY) rats. Echocardiography was performed to evaluate cardiac function and hemodynamic parameters. Hematoxylin and eosin (HE) and Masson's trichrome staining were performed, and the expression of myocardial angiotensin (Ang)-converting enzyme, chymase, transforming growth factor (TGF)-β, and collagen-type I and III were evaluated with real-time reverse transcription-PCR. Myocardial chymase, Ang-converting enzyme (ACE), and Ang II activities were measured with radioimmunoassay (RIA) techniques. Cardiac mast cells were detected with toluidine blue staining.
  
  
  RESULTS
  In SHRs, the number of chymase enzyme-positive mast cells increased in the left ventricle (LV) compared with WKY rats. QLQX significantly decreased mast cell density and cardiac chymase levels, and it improved ejection fraction values and cardiac systolic function compared with vehicle. Moreover, QLQX decreased left atrial diameters and improved the E/A ratio. QLQX suppressed collagen-type I and III and TGF-β mRNA levels, and Ang II activity, in a dose-dependent manner. Whereas no difference in ACE activity was found between SHRs, chymase expression and activity were significantly decreased with QLQX.
  
  
  CONCLUSIONS
  These data suggest that QLQX improves both systolic and diastolic cardiac function in SHRs through downregulating the cardiac chymase signaling pathway and chymase-mediated Ang II production.
authors.affiliation: Department of Cardiology, Harbin Medical University, PR China. doctor_liuwei@yahoo.com.cn
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Junjun
authors.initials: J
authors.lastname: Chen
authors.forename: Tengfei
authors.initials: T
authors.lastname: Xu
authors.forename: Wendan
authors.initials: W
authors.lastname: Tian
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D053818:Chymases / Q000037:antagonists & inhibitors*; D024042:Collagen Type I / Q000096:biosynthesis; D024061:Collagen Type III / Q000096:biosynthesis; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004452:Echocardiography; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008407:Mast Cells; D008516:Medicine, Chinese Traditional; D009206:Myocardium / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D004365:Drugs, Chinese Herbal; D016212:Transforming Growth Factor beta; C572413:qiliqiangxin; D007703:Peptidyl-Dipeptidase A; D053818:Chymases