Effect of oxymatrine, the active component from Radix Sophorae flavescentis (Kushen), on ventricular remodeling in spontaneously hypertensive rats.

PURPOSE: 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.

CONCLUSION: 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.