Objective It is to approach the improving effects of tanshinone ⅡA towards oxidative stress related cardiac hypertrophy and related mechanism.Methods The cell of cardiac hypertrophy model induced by 5-hydroxytryptamine(5-HT) was treated by different concentrations of tanshinone ⅡA.The following items were studied such as cell surface area,leucine incorporation and ROS.The ELISA and RT-PCR were employed to test the level of Apelin and Apelin mRNA.Results ①Compared with DMSO,the increased surface area of neonatal rat myocardial cells stimulated by 5-HT serotonin with the significant effects at 30 μmol/L was inhibited by tanshinone ⅡA;② The synthesis rate of protein and reactive oxygen species level were reduced by tanshinone ⅡA;③ The levels of Apelin and Apelin mRNA were elevated after tanshinone ⅡA treatment;④The effect of tanshinone ⅡA in suppressing cardiac hypertrophy was reduced by the antagonist of Apelin receptor F13A.Conclusion Tanshinone ⅡA can improve oxidative stress related cardiac hypertrophy with possible mechanism of up-regulating Apelin.

OBJECTIVE To observe the effects and mechanisms of sodium tanshinone ⅡA sulfonate(STS) on angiotensin Ⅱ(Ang Ⅱ)-induced cardiomyocyte oxidative stress.METHODS In the primary culture of neonatal rat cardiomyocytes,the content of reactive oxygen species(ROS) was measured by 2,7-dichlorofluorescein diacetate(DCFH-DA).8-hydroxydeoxyguanosine level in the supernatant was measured by ELISA.As indexes of cardiomyocyte oxidative stress,the cellular contents of MDA and SOD,cell vialibity and LDH release were measured.NADPH oxidase(NOX) activity was measured by chromatometry.The expressions of p47 phox was assessed using Western blot.RESULTS STS can decrease Ang Ⅱ-induced elevations of ROS level and oxidative stress,and inhibit the expression of p47 phox and NOX activity.CONCLUSION The inhibitory effects of STS on Ang Ⅱ-induced cardiomyocyte oxidative stress may be associated with depressing NOX signaling pathway via down regulation of p47 phox expression.

OBJECTIVE:To explore the effects of Tanshinone II A (Tan II A) on the myocardial apoptosis in rats with heart failure and its mechanisms for regulating the miR- 133 levels.METHODS:The heart failure rat model was established by thoracic aorta constriction (TAC). Tan II A Injection was applied for 12 successive weeks. Meanwhile, partial heart failure rats were subcutaneously implanted with osmotic pump of antagonist to observe its inhibition on the miR-133 level. Twelve weeks later, the hemodynamic conditions, the myocardial apoptosis (using TUENL method), myocardial pro-apoptotic genes (Bax and Caspase-3), and the expressions of anti-apoptosis genes (Bcl-2) (using Western blot and RT-PCR method) were analyzed.RESULTS:Compared with the sham-operation group, TAC operation could deteriorate the heart function (except the mean arterial pressure), elevate the myocardial apoptosis level, increase the protein and mRNA levels of Bax and Caspase-3, and down-regulate the protein and mRNA levels of miR-133 and Bcl-2. TAC rats treated by Tan II A could significantly improve all indices with statistical difference except the heart rate. Subcutaneously pumping of antagonist could partially abolish the anti-apoptosis effect of Tan II A.CONCLUSION:Tan II A could decrease the myocardial apoptosis level of heart failure rats, which was possibly realized by up-regulating the miR-133 level.

Objective To explore the inhibition effect of Apelin on the oxidative stress related cardiac hypertrophy and the possibly mechanism.Methods The 5-HT was applied to induce the cardiac hypertrophic cells with neonatal rat cardiac myocytes,which was divided into control group,Apelin activation group,inhibition group(DETC or ATZ),and combination group.Theβ-liquid scintillation counter was used to detect the[~3H]leucine incorporation and imunohistochemical staining was used to analyze the cell surface area.The intracellular ROS was detected by CM-H_2DCFDA.The kits were used to detect the intracellular H_2O_2 levels,lipid peroxide(LPO)levels,catalase(CAT)and glutathione peroxidase(GPx)activity.Besides, the level of CAT mRNA and GPx mRNA levels were detected by RT-PCR.Results(1)Compared with control group,the Apelin reduced the[~3H]leucine incorporation and cell surface of cardiac hypertrophic cells in a dose dependent manner with the strongest effect at 50μmol/L(P<0.05);(2)The concentration of 50μmol/L Apelin could reduce the level of intracellular ROS(P<0.05),but the pretreatment with DETC significantly inhibited the effects of Apelin(P<0.05);(3) The concentration of 50μmol/L Apelin could reduce the level of intracellular H_2O_2,and the pretreatment with ATZ inhibited the effects of Apelin(P<0.05);(4)The concentration of 50μmol/L Apelin treatment could result in the improvement of the CAT activity,mRNA levels increased,while the LPO,GPx activity and mRNA levels did not have difference(P>0.05),while the pretreatment with ATZ significantly inhibited the CAT activity,mRNA levels increase(P<0.05).Conclusion It demonstrated that the Apelin inhibit the oxidative stress related cardiac hypertrophy,with the possibly mechanism was the activation of catalase.

Objective It is to observe the action of tanshinone on electrophysiological abnormality and calcineurin(CaN) activity in hypertrophy cardiomyocyte.Methods The influence of tanshinone on action potential duration,L-type calcium channels current(ICa,L),intra-cellular calcium ion concentration and CaN activity in cellular membrane of hypertrophic myocardium induced by the surgery of "one kidney one clamp" was observed through patch clamp,intra-cellular calcium mensuration and molecular biological technique.Results Tanshinone could markedly shorten the prolongation of action potential duration(P<0.001),lower membrane capacity and peak amplitude of ICa,L(P<0.001) and markedly reduce intra-cellular calcium ion concentration,but not affect the density of ICa,L.Tanshinone could markedly inhibited CaN expression of hypertrophic myocardium(P<0.05).Conclusion Tanshinone can effectively reduce calcium ion concentration,inhibit L-type calcium channels and lower CaN activity in hypertrophic cadiocyte so that it may improve electrophysiological abnormality and alleviate the occurrence of myocardial hypertrophy.

Objective To observe the effect of sodium tanshinone ⅡA sulfonate (STS) on angiotensin receptor and signal transducers and activators of transcription (STAT3) of myocardial hypertrophy due to pressure overload and explore the molecular biological mechanism by which STS could postpone myocardial hypertrophy. Methods Twenty four SD rats at 9 weeks old,suffered from abdominal aorta constriction,were randomly divided into three groups:model group (n=8),STS treatment group treated by ip injection of STS [10 mg/(kg·d)] (n=8),and Valsatan [10 mg(/kg·d)] treament group. Another eight rats,which were suffered from artificial surgery,as a Sham group (n=8). Tail artery systolic blood pressure (SBP) and left ventricular mass index (LVMI) were measured,and the myocardial fiber diameter (MFD) was detected by HE and VG staining. Protein expressions of AT1R and STAT3 were assessed by Western blotting and AT1R mRNA by RT-PCR. Results Compared to the Sham group,the SBP,LVMI,MFD,AT1R mRNA,and STAT3 expressions markedly increased in model group (P0.05). All items of above mentioned in STS group were lower than those in model group (P0.05). Conclusion STS could postpone the progress of myocardial hypertrophy by downregulating the expression of AT1R receptors and STAT3.

Objective:To study the effects of Tanshinone on the vasoactive peptides in the plasma of spontaneously hypertensive rats(SHR) for example:endothelin,angiotensinⅡand atrial natriuretic factor.Methods:Twenty four male SHR were randomly divided into positive control group,Tanshinone group and Valsartan group.Eight male Wistar rats were as a normal control group.After 4 weeks intervention,blood pressure of the rat tail,weight of myocardium and the contents of endothelin,angiotensinⅡ and atrial natriuretic factor were measured.Results:After 4 weeks intervention,the blood pressure of Tanshinone group and Valsartan group decreased than positive control group(P 0.01).The ventricle weights and ventricle weight/body weight index of positive control group were higher than other groups(P 0.05).The contents of endothelin,angiotensinⅡ and atrial natriuretic factor in Tanshinone group and Valsartan group were lower than positive control group(P 0.05).Conclusion:Tanshinone could decreased the contents of endothelin,angiotensinⅡ and atrial natriuretic factor in the plasma of spontaneously hypertensive rats,and which might be attenuated ventricular hypertrophy.

目的 观察丹参酮ⅡA磺酸钠(sodium tanshinone ⅡA sulfonate,TSN) 对腹主动脉缩窄高血压大鼠肥厚心肌的作用以及对细胞内游离钙离子浓度、Janus激酶及其信号转导子和激活子(JAK/STAT)的影响.方法 SD大鼠行腹主动脉缩窄术建立高血压左室心肌肥厚模型,随机分为心肌肥厚组(n=8)、丹参酮ⅡA组(n=8)和缬沙坦组(n=8);另取8只行假手术.用药8周后通过超声心动图测定左室后壁、室间隔的厚度;测量大鼠的尾动脉收缩压(SBP)和左室质量指数(LVMI);HE染色检测心肌细胞的直径(MDF);激光共聚焦显微镜测定心肌细胞内游离Ca2+浓度的变化;Western blot方法测定各组大鼠JAK1和STAT3的表达.结果 ①TSN对血压没有影响,显著高于假手术组和缬沙坦组(P<0.01).②TSN组和缬沙坦组的左室后壁、室间隔厚度、LVMI、MFD虽然高于假手术组(P<0.05),却显著低于手术组(P<0.01).③TSN与缬沙坦均可显著降低肥厚心肌的[Ca2+]i,丹参酮对[Ca2+]i 的影响显著超过缬沙坦(P<0.05).④与假手术组相比,肥厚心肌的JAK1和STAT3蛋白表达显著升高(P﹤0.05);丹参酮ⅡA、缬沙坦均可显著降低肥厚心肌JAK1和STAT3的蛋白水平.结论 JAK/STAT的表达在心肌肥厚的信号通路中起着重要的作用;丹参酮ⅡA可能是通过降低心肌细胞[Ca2+]i浓度、阻滞JAK/STAT信号通路的转导,起到抑制心肌肥厚的作用.

Objective To elucidate the possible mechanism about tanshinone resisting ventricular remodeling by studying the effect of high salt diet on rennin-angiotensin-aldosterone system in rat heart and cardiac structure,and the change of related data after tanshinone intervention.Methods SD rats were divided into three groups: normal group,high salt group,and tanshinone group.The systolic blood pressure,left ventricular weight index(LVWI),the content of aldosterone in heart,and the expression levels of aldosterone synthase(CYP11B2) and angiotensin type 1 receptor(AT1R) in the cardiac tissue of every group were measured.Results There was no significant difference in blood pressure among the three groups.The LVWI and aldosterone content in heart were obviously increased in high salt group as compared with normal group(P<0.05),and were decreased significantly in tanshinone group as compared with high salt group(P<0.05).Plasma rennin and aldosterone concentrations were significantly lower in high salt group than in normal group(P<0.05).The expression of CYP11B2 mRNA and AT1R mRNA in cardiac tissue was obviously increased in high salt group as compared with that in normal group(P<0.05).Tanshinone could inhibit the high expression of CYP11B2 mRNA and AT1R mRNA in hypertrophic myocardium.Conclusion Tanshinone could inhibit cardiac aldosterone synthesis and AT1R expression to insist myocardial hypertrophy caused by high salt intake.

Objective:To explore the depressant effect of TSNⅡA( Tanshinone ⅡA) on myocardial hypertrophy induced by angiotensin Ⅱ(Ang Ⅱ) in cultured neonatal Wistar rat myocardical cells.Methods:The cultured neonatal rat cardiomyocytes were treated with AngⅡ(10-6mol·L-1),TSNⅡA(10-8mol·L-1),and AngⅡ(10-6mol·L-1)+ TSNⅡA(10-8mol·L-1) respectively in free-serum medium for 36 h. The cell size,3H-Leucine incorporation and total protein level were investigated.Results:TSNⅡA could antagonize the AngⅡ induced increas the cell size,3H-Leucine incorporation and total protein level.Conclusions:TSNⅡA prevens cardiomyocytes from hypertrophy induced by AngⅡ.

Background Left ventricular hypertrophy(LVH) is a cardiovascular risk factor independent of the blood pressure. JAK/STAT pathway has been confirmed to participate in cardiac hypertrophy and hyperplasia. Our previous reports have shown that sodium tanshinone ⅡA sulfonate(STS) reversed LVH,inhibited the myocardial cells Ca2+ influx,lowered left ventricular myocardial tumor necrosis factor-α(TNF-α)and the proto-oncogene c-fos,Bcl-2,and p53 protein expression. Objective To study the effect of sodium tanshinone ⅡA sulfonate(STS) on JAK/STAT pathway in left ventricular hypertrophy(LVH) induced by abdominal aorta stenosis in rats. Methods Twenty-four 9-weeks-old rats submitted to abdominal aorta constriction,were randomized to receive STS 10 mg/(kg·d)(n=8)or sterilized distilled water (1 mL/d)(n=8),or valsartan 10 mg/(kg·d) by gavage(n=8),with age and sex matched sham operated rats(n=8) as control. HE,VG and immunohistonchemical staining were used to evaluate the myocardial fiber dimension(MFD). Expressions of JAK1 and STAT3 were assessed by using Western blot. Results Compared with the control group,pressure loaded rats had higher SBP[(117.3±8.3) vs LVH: (186.5±13.5)mmHg,P<0.05],LVMI[(1.60±0.03) vs LVH:(2.1±0.1)mg/g,P<0.05],MFD[(10.2±0.9) vs LVH: (18.1±1.3)μm,P<0.05],JAK1[(0.32±0.04) vs LVH: (0.69±0.16),P<0.05]and STAT3[(0.55±0.14) vs LVH: (0.74±0.08),P<0.05]. STS and valsartandecrease JAK1[(0.69±0.16) vs STS: (0.63±0.16) vs valsartan: (0.46±0.07),P<0.05]and STAT3 expressions[(0.74±0.08) vs STS: (0.70±0.06) vs valsartan: (0.59±0.08),P<0.05]. Conclusion Long-term use of STS or Valsartan inhibit the development of LVH which is associated with decreasing the expression of JAK1,STAT3.

Cardiac fibrosis occurs after pathological stimuli to the cardiovascular system. One of the most important factors that contribute to cardiac fibrosis is angiotensin II (Ang II). Accumulating studies have suggested that reactive oxygen species (ROS) plays an important role in cardiac fibrosis and sodium tanshinone IIA sulfonate (STS) possesses antioxidant action. We therefore examined whether STS depresses Ang II-induced collagen type I expression in cardiac fibroblasts. In this study, Ang II significantly enhanced collagen type I expression and collagen synthesis. Meanwhile, Ang II depressed matrix metalloproteinase-1 (MMP-1) expression and activity. These responses were attenuated by STS. Furthermore, STS depressed the intracellular generation of ROS, NADPH oxidase activity and subunit p47(phox) expression. In addition, N-acetylcysteine the ROS scavenger, depressed effects of Ang II in a manner similar to STS. In conclusion, the current studies demonstrate that anti-fibrotic effects of STS are mediated by interfering with the modulation of ROS.

To investigate the molecular mechanism by which Tanshinone IIA (TSN IIA) prevents left ventricular hypertrophy (LVH), we examined the expression of AT1R, TGF-β1 and Smads gene in the hypertrophic myocardium of hypertensive rats with abdominal aorta constriction. LVH model was established by creating abdominal aorta constriction. Four weeks later, animals were randomly divided into 4 groups with 8 animals in each. One group was used as model control, the other three groups were treated with TSN IIA (20 mg/kg), TSN IIA (10 mg/kg) and valsartan (10 mg/kg), respectively. Another 8 SD rats were subjected to sham surgery and served as blank control. After 8-week treatment, the caudal artery pressure of the animals was measured. The tissues of left ventricle were taken for the measurement of the left ventricular mass index (LVMI) and pathological sectioning and HE-staining were used for determining the myocardial fiber dimension (MFD). The mRNA expression of AT1R, protein expression of TGF-beta1 and activity of Smad-2, 4, 7 were detected by RT-PCR and Western blotting, respectively. Our results showed that (1) the blood pressure of rats treated with TSN IIA, either at high or low dose, was significantly higher than those in the control and valsartan-treated group (P<0.01, P<0.05); (2) LVMI and MFD in TSN IIA and valsartan-treated rats were higher than those in the control group (P<0.05) but significantly lower than those in the model control (P<0.01); (3) the high doses of TSN IIA and valsartan significantly down-regulated the mRNA expression of AT1R and protein expression of TGF-beta1 and Smad-3 in the hypertrophic myocardium (P<0.01), and TGF-beta1 in valsartan-treated animals was more significantly lower than that in rats treated with TSN IIA; (4) the two doses of TSN IIA and valsartan significantly up-regulated the protein expression of Smad-7 in the hypertrophic myocardium (P<0.01), and Smad-7 in the animals treated with high-dose TSN IIA was significantly higher than that in rats treated with valsartan. It is concluded that inhibition of myocardial hypertrophy induced by TSN IIA independent of blood pressure. The underlying mechanism might be the down-regulated expression of AT1R mRNA and Smad-3, increased production of Smad-7, and blocking effect of TSN IIA on TGF beta1/Smads signal pathway in local myocardium.

Tanshinone IIA, one of the main active components from the Chinese herb Danshen, is widely used to treat cardiovascular diseases in Asian countries, especially in China. To further elucidate its heart rate–reducing and anti-ischemic mechanisms, here we investigated the effects of tanshinone IIA on hyperpolarization-activated cyclic nucleotide–modulated (HCN) channels expressed in Xenopus oocytes using two-electrode voltage clamp techniques. When applied to the extracellular solution, 100 μM tanshinone IIA caused a slowing of activation and deactivation and an increase of minimum open probabilities (from 0.06 ± 0.01 to 0.29 ± 0.03, P<0.05) in HCN2 channels without shifting the voltage dependence of channel activation. Tanshinone IIA potently enhanced the amplitude of voltage-independent current (instantaneous current) of HCN2 at −90 mV in a concentration-dependent manner with an EC50 of 107 μM. Similar but 2.3-fold less sensitivity to tanshinone IIA was observed in the HCN1 subtype. More significant effect on HCN2 and MiRP1 co-expression was observed. In conclusion, tanshinone IIA changed HCN channel gating by selectively enhancing the instantaneous current (one population of HCN channels), which resulted in the corresponding increment of minimum open probabilities, slowing channel activation and deactivation processes with little effect on the voltage-dependent current (another population of HCN channels).

The effects of tanshinone II A on cell signal transduction system protein kinase B in rats with myocardial hypertrophy induced by the abdominal aorta partial coarctation were investigated. Rat models of myocardial hypertrophy were established by using abdominal aorta partial coarctation method. Forty-eight rats were randomly divided into sham group (S group), model group (M group), valsartan treatment group (X group), low-dose tanshinone treatment group (LD group), medium-dose tanshinone treatment group (MD group), and high-dose tanshinone treatment group (HD group) (n = 8 in each group). Left ventricular mass index (LVMI), left ventricular posterior wall (LVPW), and septal thickness (IVS) were detected by high frequency ultrasonography. Myocardial fiber diameter (MFD) was examined by Hematoxylin-Eosin (HE) staining, and the contents of phosphorylated protein kinase B (p-Akt) and p-Gsk3β in myocardium were assayed by Western blot. The results showed that compared with S group, the values of LVMI, LVPW, IVS and MFD were increased in other groups (P<0.05), and the contents of p-Akt, and p-Gsk3β were also increased in other groups. As compared with MD group, the values of LVMI, LVPW, IVS and MFD were decreased in all treatment groups (P<0.05), and the contents of p-Akt, and p-Gsk3β were also decreased in all treatment groups. However, there were no significant differences among LD, MD, and HD groups (P>0.05), and there were no significant differences between X group and tanshinone treatment groups (P>0.05). It was suggested that tanshinone II A could prevent myocardial hypertrophy by its action on the Akt signaling pathway.

Objective To study the intervention effect of tanshinone on electrophysiological abnormality of hypertrophic cardicoyte in order to illuminate the underlying mechanism of tanshinone in preventing the arrhythmia induced by myocardial hypertrophy. Method Twenty-week-rid SD rats (200～250 g) were divided into 4 groups (8 in each group) randomly. Of 4 groups, rats of three groups were operated on by a procedure of 'one kidney one clamp' to make renal artery constriction. The rest group served as sham operation group (control group). When the blood pressure increased,rats of operation groups were divided into tanshinone group, captopril group and hyper-trophic group. The effects of tanshinoe and captopril were observed and compared on the action potential duration (APD),L-type calcium current (ICa, L) and transient outward potassium current (Ito) density in cellular membrane of hypertrophic myocardium by using patch clamp and intra-cellular calcium survey technique. Results The blood pressure in operation groups was obviously higher than that in sham-operation group (P<0.01), but there was no difference between operation groups (P>0.05). The ratio of ventricle weight to body weight (VW/BW) was much higher in hypertrophic group than in control group (P<0.01), and it significantly decreased after interven-tion with tanshinone or captopril (P<0.01). Compared with hypertrophic group, tanshinone markedly shortened the prolongation of action potential duration (P<0.01), decreased membrane capacity and peak amplitude of ICa,L(P<0.01), but had no effect on the density of ICa,L. Tanshinone also significantly increased Ito current density and peak amplitude, which were completely different from hypertrophic group (P<0.05). There were similar results foundin captopril intervention. Conclusions Tanshinone could reduce calcium influx and resume the activity of ho ion channels, and thus shorten the first phase and the plateau phase of repolarization and decrease the prolongation of APD in hypertrophic cadiocyte. So tanshinone can prevent the onset of arrhythmia attributed to the myocardial hypertrophy.

OBJECTIVE To explore the molecular mechanism for tanshinone ⅡA reversing left ventricular hypertrophy,which involved the effect of tashinone on the angiotensin Ⅱ type 1 receptor and endothelial nitric oxide synthase(eNOS) and protein kinase C(PKC) in the hypertrophic cadiocyte of rats suffered abdominal aorta constriction.METHODS SD rats were operated with abdominal aorta constriction and 8 rats were done with artificial surgery.After 4 weeks,all rats were divided into 4 groups: myocardial hypertrophy group,low dose tanshinone ⅡA group(10 mg·kg-1·d-1,ip),high dose tanshinone ⅡA group(20 mg·kg-1·d-1,ip) and valsartan group(10 mg·kg-1·d-1,ig).Eight weeks later,measuring the left ventricular mass index(LVMI) with the tissue of left ventricle and myocardial fiber dimension(MFD) by pathological section and HE stain.To detect the nitric oxide content by nitrate reductase,to detect the genic expression of AT1 receptor by RT-PCR and to detect the activity of eNOS and PKC by Western blotting.RESULTS ①The tanshinone ⅡA at either low or high dosage has not effect on the blood pressure,which remains significantly hihgher than the artificial surgery and valsartan groups(P0.01).②The LVMI and MFD in both tanshinone ⅡA at either dosage and valsartan groups are significantly lower than those of the surgery group(P0.01),although higher than the artificial surgery group(P0.05).③The amount of NO and eNOS expression in both tanshinone ⅡA at either dosage and valsartan groups are higher than the surgery group(P0.01),and the up-regulation of eNOS in tanshinone ⅡA group at either dosage is more prominent than in valsartan group(P0.05).④Tanshinone ⅡA at either dosage could significantly down-regulate the AT1R mRNA and PKC level in the hypertrophic cardiomyocyte(P0.01),with more prominent effect on down-regulating PKC expression than valsartan group(P0.05).CONCLUSION NO/NOS system in local myocardium had close relationship with the pathological process for myocardial hypertrophy.Tanshinone ⅡA could produce the pharmacological action to reverse myocardial hypertrophy by downregulating the genic expression of AT1 receptor and inhibiting the activity of PKC and promoting the genic expression of eNOS in local myocardium and the production of endogenous NO.

To observe the effects of sodium tanshinone II A sulfonate (STS) on angiotensin II (Ang II)-induced hypertrophy of myocardial cells through the expression of phosphorylated extracellular signal-regulated kinase (p-ERK1/2).

OBJECTIVE:To explore the molecular biological mechanism for tanshinone II A reversing left ventricular hypertrophy, it would be studying the effect of tashinone on the endothelial nitric oxide synthase (eNOS) and protein kinase C (PKC) in the hypertrophic cadiocyte of rats suffered abdominal aorta constriction.METHOD:SD rats were operated with abdominal aorta constriction and 8 rats were done with sham surgery. After 4 weeks, all rats were divided into 4 groups: myocardial hypertrophy group, low dose tanshinone II A group (10 mg x kg(-1) x d(-1)), high dose tanshinone II A group (20 mg x kg(-1) x d(-1)) and valsartan group (10 mg x kg(-1) d(-1) intragastric administration). 8 weeks later, the rats were used to measure the left ventricular mass index (LVMI) with the tissue of left ventricle and myocardial fiber dimension (MFD) by pathological section and HE stain, to detect the nitric oxide content by nitrate reductase, to detect the genic expression of eNOS by RT-PCR and to detect the activity of protein kinase C (PKC) by Western blotting.RESULT:1) The blood pressure in group myocardial hypertrophy [(186 +/- 13) mmHg] and tansginone II A [low and high dose (188 +/- 11,187 +/- 14) mmHg] was obviously higher than that in group sham surgery and valsartan group [vs (117 +/- 8, 136 +/- 15) mmHg, P < 0.01]. But there was no difference between group myocardial hypertrophy and group tanshinone II A (low and high dose). 2) The LVMI and MFD were obviously higher in group tanshinone II A low and high dose) and group valsartan than those in group sham surgery (P < 0.05), and lower than those in group myocardial hypertrophy (P < 0.01). 3) The NO level was obviously higher in group tanshinone II A (low and high dose) and group valsartan than that in group myocardial hypertrophy (12.78 +/- 1.66, 11.95 +/- 1.39, 12.26 +/- 2.08 vs 5.83 +/- 1.06) micromol x L(-1), (P < 0.01 ), and lower than that in group sham surgery (vs 19.35 +/- 1.47) micromol x L(-1), (P < 0.05). 4) The expressive level of eNOS mRNA and protein in myocardial hypertrophy group was less than that in other groups (P < 0.01). And valsartan group was less than tanshinone II A groups and sham surgery group (P < 0.05), but there were no difference among the two tanshinone II A groups and sham surgery group. 5) The level of PKC protein in group myocardial hypertrophy was obviously higher than that in all the other groups (1.291 +/- 0.117 vs 0.563 +/- 0.094, 0.605 +/- 0.051, 0.519 +/- 0.062, 0.827 +/- 0.086, P < 0.01), and the level in group valsartan was higher than that in group sham operation and group tanshinone II A (low and high dose).CONCLUSION:NO/NOS system in local myocardium has close relationship with the pathological process for myocardial hypertrophy. Tanshinone II A can produce the pharmacological action to reverse myocardial hypertrophy by inhibiting the activity of PKC and promoting the genic expression of eNOS in local myocardium and the production of endogenous NO.