title: Effect of oxymatrine, the active component from Radix Sophorae flavescentis (Kushen), on ventricular remodeling in spontaneously hypertensive rats.
abstract: OBJECTIVE
  To examine the effects of oxymatrine (OMT) on ventricular remodeling in spontaneous hypertension rat (SHR) and the underlying mechanism.
  
  
  METHODS
  SHRs were divided into four groups: SHR control, SHR+40 mg/kg captopril, SHR+30 mg/kg OMT and SHR+60 mg/kg OMT. Normotensive age-matched WKY rats were assigned to two groups: WKY control, WKY+30 mg/kg OMT. The rats were orally administered with the corresponding drugs or drinking water for 21 weeks. Mean arterial blood pressure (MAP) and heart rate (HR) were measured. The left ventricular weight index (LVWI) and heart weight index (HWI) were determined. Myocardium tissue was stained with picric acid/Sirius red for measurement of collagen content measurements. The concentrations of serum norepinephrine and angiotensin II (Ang II) in myocardium were determined. Real-time RT-PCR was used to detect the mRNA expressions of transforming growth factor-β1 (TGF-β1), collagen types I, III and angiotensin converting enzyme (ACE). Western blots were performed to determine bioactivities of extracellular signal regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK/SAPK), p38 mitogen-activated protein kinases (p38 MAPK) and phospho-speciﬁc protein kinase C (PKC).
  
  
  RESULTS
  In the SHR, hypertension, myocardium hypertrophy, more cardiac fibrosis, higher concentrations of serum norepinephrine and myocardium Ang II were observed. OMT treatment lowered the blood pressure, reduced the concentrations of serum norepinephrine and myocardium Ang II, favorably decreased the measured gravimetric parameters, decreased the interstitial and perivascular collagen deposition, attenuated the collagen of type I and III accumulation, downregulated the mRNA expression of ACE and TGF-β1, and suppressed the phosphorylation of ERK 1/2, JNK and p38 MAPK in SHRs.
  
  
  CONCLUSIONS
  OMT prevents ventricular remodeling in SHR. The mechanisms may be related to inhibiting the gene overexpression of ACE and TGF-β1, suppressing the activation of signaling pathways of ERK 1/2, JNK and p38 MAPK.
authors.affiliation: Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Xiao Yan
authors.initials: XY
authors.lastname: Huang
authors.forename: Chang Xun
authors.initials: CX
authors.lastname: Chen
mesh_terms: D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D008517:Phytotherapy; D011807:Quinolizines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects*; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000804:Angiotensin II; D000889:Anti-Arrhythmia Agents; D003094:Collagen; D004365:Drugs, Chinese Herbal; D009638:Norepinephrine; D007703:Peptidyl-Dipeptidase A; D011807:Quinolizines; D053773:Transforming Growth Factor beta1; C508962:Tgfb1 protein, rat; C037573:oxymatrine; D000093842:Matrines; C494416:kushen