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To investigate the effects of leonurine(Leo) on abdominal aortic constriction(AAC)-induced cardiac hypertrophy in rats and its mechanism. A rat model of pressure overload-induced cardiac hypertrophy was established by AAC method. After 27-d intervention with high-dose(30 mg·kg~(-1)) and low-dose(15 mg·kg~(-1)) Leo or positive control drug losartan(5 mg·kg~(-1)), the cardiac function was evaluated by hemodynamic method, followed by the recording of left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVESP), as well as the maximum rate of increase and decrease in left ventricular pressure(±dp/dt_(max)). The degree of left ventricular hypertrophy was assessed based on heart weight index(HWI) and left ventricular mass index(LVWI). Myocardial tissue changes and the myocardial cell diameter(MD) were measured after hematoxylin-eosin(HE) staining. The contents of angiotensin Ⅱ(AngⅡ) and angiotensin Ⅱ type 1 receptor(AT1 R) in myocardial tissue were detected by ELISA. The level of Ca~(2+) in myocardial tissue was determined by colorimetry. The protein expression levels of phospholipase C(PLC), inositol triphosphate(IP3), AngⅡ, and AT1 R were assayed by Western blot. Real-time quantitative PCR(qRT-PCR) was employed to determine the mRNA expression levels of β-myosin heavy chain(β-MHC), atrial natriuretic factor(ANF), AngⅡ, and AT1 R. Compared with the model group, Leo decreased the LVSP, LVEDP, HWI, LVWI and MD values, but increased ±dp/dt_(max) of the left ventricle. Meanwhile, it improved the pathological morphology of myocardial tissue, reduced cardiac hypertrophy, edema, and inflammatory cell infiltration, decreased the protein expression levels of PLC, IP3, AngⅡ, AT1 R, as well as the mRNA expression levels of β-MHC, ANF, AngⅡ, AT1 R, c-fos, and c-Myc in myocardial tissue. Leo inhibited AAC-induced cardiac hypertrophy possibly by influencing the RAS system.

Fibroblast growth factor 23 (FGF23) is a hormone secreted by the bone. It is not only involved in the pathophysiological process of chronic kidney disease (CKD), but also associated with the poor prognosis. In patients with CKD, serum FGF23 levels are elevated in early phase. The increased FGF23 levels gradually lead to myocardial hypertrophy, inflammatory, vascular calcification, and low level of vitamin D, which contribute to the progress of CKD, cardiovascular complications and even death. Presently, there are several ways to reduce FGF23 levels, including decrease of intake and block of phosphorus absorption, supplement of FGF23 antibody and pseudo calcium or renal transplantation.

Objective: To investigate the role of Mic60 in cardiac aging. Methods: Wild-type and Mic60(+ /-) male mice at age of 4-6 months (young group, n =6) and 18-20 months (aged group, n =9) were used. H&E and Masson staining of frozen and paraffin sections were subjected to morphologic evaluation of the cardiac tissue samples. SA-β-Gal staining was utilized to detect the activity of senescence-associated β-galactosidase. Western blot was performed to detect the expression of Mic60 and p21 in cardiac tissues. Results: Expression of Mic60 in mouse cardiac tissue increased in an age-dependent manner. Haploid insufficiency of Mic60 resulted in an increased left ventricular wall thickness [(1.32±0.09) mm vs .(1.12±0.09) mm, P <0.05], cardiomyocyte hypertrophy[(474.9±27.6) μm(2) vs .(358.8±48.7) μm(2), P <0.05] and interstitial fibrosis [ (38.24±7.58) ×10(3)μm(2) vs .(25.81±4.12)×10(3)μm(2,) P <0.05], increased activity of SA-β-Gal (2.26±0.24 vs .0.25±0.05, P <0.01) and higher expression of p21 ( P <0.01) in aged mouse cardiac tissue, but not in young mice. Conclusion: Haploid insufficiency of Mic60 leads to cardiac hypertrophy, interstitial fibrosis, increased activity of SA-β-Gal and higher expression of p21 in aged cardiac tissue in mice, suggesting that Mic60 may prevent cardiac aging.

Objective: To observe the effect of Cornus officinalis fruit core extract on cardiac hypertrophy induced by two kidney two clip (2K2C) and its mechanism., Methods: Male Sprague-Dawley rats were randomly divided into 4 groups: sham-operated group, model group and treatment groups (300, 600 mg/kg). Rats were intragastric administered medicine for 4 weeks from the fourth week after surgery. Sham-operated and 2K2C rats were given vehicle for 4 weeks. Blood pressure and hemodynamic parameters were measured. Left ventricular weight to body weight (LVM/BM) ratio was calculated. Paraffin-embedded hearts were cut into 5 microm slices, which were stained with hematoxylin-eosin (HE) and Masson for morphological analysis; Western-blot analysis was performed to investigate the effects of Cornus officinalis fruit core extract on the expression of P47phox, Nox4 in myocardium., Results: Compared with sham-operated group, the blood pressure and LVM/BM ratios were markedly elevated in model groups. Meanwhile cardiomyocyte cross sectional areas was markedly increased and myocardial fibers showed disordered arrangement while these parameters were markedly reversed after treatment with Cornus officinalis fruit core extract for 4 weeks. At 8th weeks after operation, model rats developed obvious LV hypertrophy. Cornus officinalis fruit core extract, more significant in high dose, decreased the blood pressure and LVM/BM ratios and reversed the cardiomyocyte hypertrophy and myocardial fibrosis. Moreover, Cornus officinalis fruit core extract decreased the expression of P47phox and Nox4 which elevated in LV in model rats., Conclusion: Cornus officinalis fruit core extract could significantly decrease the blood pressure, reverse cardiac hypertrophy and improve the function of heart which is possibly associated with the down-regulation of P47phox and Nox4.

To investigate the cellular mechanisms of pressure-overload cardiac hypertrophy transition to heart failure, we observed time course of changes in morphology and contractile function of cardiomyocytes in transverse abdominal aortic constriction (TAC) rats. Since TAC rats suffered higher stress, body weight had a slower growth rate compared with that of synchronous control rats. Therefore, the left ventricular to body weight ratio produced experimental bias to evaluate the degree of cardiac hypertrophy. Length and width of collagenase-isolated cardiomyocyte were directly measured. Length, width and calculated surface area of cardiomyocyte showed a progressive increase in 8-, 16-, and 20-week TAC rats. The increasing rate of surface area in cardiomyocytes was higher at the middle stage of TAC (from the eighth to sixteenth week). Due to the constraint of fibrosis formation, the increasing rate of surface area in cardiomyocytes was slower at the late stage of TAC (from the sixteenth to twentieth week). The sarcomere length of cardiomyocytes was unchanged, whereas sarcomere numbers were significantly increased in 8-, 16-, and 20-week TAC rats. Shortening amplitude of unloaded contraction in single cardiomyocyte was significantly enhanced in 1-week TAC rats, but not altered in 8-week TAC rats compared with that in the synchronous control rats. On the contrary, unloaded shortening amplitude of single cardiomyocyte was significantly reduced in 16- and 20-week TAC rats. The above results suggest that the reduced shortening amplitude may be associated with intrinsic molecular alterations in hypertrophied cardiomyocytes.

Objective: To investigate the molecular mechanism of tanshinone II A (TSN) for preventing left ventricular hypertrophy (LVH) by studying the expressions of angiotensin I type 1 receptor (AT1R), transforming growth factor beta1 (TGF-beta1) and intracellular signal protein gene (Smads gene) in the hypertrophic myocardium of hypertensive rat models induced by pressure over-loading., Methods: SD rat model of LVH was established by abdominal aorta constriction. The model animals were randomly divided into 4 groups 4 weeks after modeling, the untreated model control group (C1), the two tested groups (T1 and T2) treated respectively with high (20 mg/kg) and low (10 mg/kg) dose of TSN II A per day via intraperitoneal injection, and the positive control group (C2) treated with 10 mg/kg of Valsartan per day by gastric perfusion, with 8 animals in each group. Besides, 8 SD rats managed with sham operation were set up as the sham-operated control group (C3) After an 8-week treatment, the caudal arterial pressure, left ventricular mass index (LVMI), myocardial fiber dimension (MFD, by pathologic examination with HE staining) in rats were measured. Meanwhile, mRNA expression of AT1R, protein expression of TGF-beta1 and activity of Smad-3, 4, 7 in the ventricular tissue were detected by RT-PCR analysis and Western blotting respectively., Results: (1) Blood pressure in Group T1 and T2 was unchanged after treatment, which was significantly higher than that in Group C2 and C3 (P < 0.01, P < 0.05). (2) LVMI and MFD in Group T1, T2 and C2 were higher than that in Group C3 (P < 0.01), but remarkably lower than that in Group C1 (P < 0.01). (3) Levels of AT1R, TGF-beta1 and Smad-3 expression increased significantly in the model rats (P < 0.01), but they were down-regulated in Group T1 and C2, and the TGF-beta1 regulating effect in the C2 was more potent than that in Group T1 and T2 (P < 0.05). (4) Protein expression of Smad-7 was up-regulated in Group T1, T2 and C2 obviously (P < 0.01), and the effect in Group T1 was superior to that in C2 (P < 0.05)., Conclusion: The myocardial hypertrophy inhibition effect of TSN II A is a blood pressure independent process, and it may be related to the inhibition of AT1R mRNA expression and blocking of TGF beta1/Smads signal pathway.

Objective: To compare the effects of amlodipine, benidipine and nifedipine on myocardial hypertrophy and evaluate the underlying mechanism., Methods: Myocardial hypertrophy model was created by transverse aortic constriction (TAC) in C57 BL/6 mice, and plasma catecholamine concentrations were measured 7 days after surgery to confirm the sympathetic activation. The 3 drugs were administered in TAC mice for 7 days and cardiac hypertrophy was evaluated according to the heart-to-body weight ratio (HW/BW). Effects of those drugs on the protein synthesis stimulated by phenylephrine in cultured neonatal cardiac myocytes were also examined., Results: HW/BW and plasma concentrations of catecholamine were significantly increased in TAC mice one week after surgery in comparison with to sham-operated mice. One week after TAC, the HW/BW ratio was significantly lower in the amolodipine but not nifedipine-treated group than in the TAC group. Administration of nifedipine via minipump infusion for one week did not decrease HW/BW ratio. Treatment with amlodpine or benidipine, but not nifedipine, decreased the neonatal rat myocyte protein synthesis induced by phenylephrine stimulation., Conclusion: Antihypertrophic effect of DHEs on myocardium is dependent on their potential of blocking N-type calcium channel, and the underlying mechanism involves the sympathetic inhibition.

This experiment on rats was aimed to investigate the expression of intermedin (IMD) in hypertrophic cardiac myoctye of renal vascular hypertension induced by incomplete ligation of the left renal artery, and so to detect and compare the changes of the expression after administration of Valsartan, Amlodipine and Enalapril respectively. The criterion for standard modeling was systolic pressure > or = 140 mmHg. At 4 weeks after successful modeling, 60 SD male rats were randomly divided into 5 groups, namely the hypertrophy group, the 3 drug-treatment groups, and the sham-operation group as control. Blood pressure, left ventricular mass index (LVMI), and the left ventricular mean transverse diameter of myocardial cell (LVTDM) were investigated at the 10th week after model establishment. Gene expression of IMD mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR), and the optical density of the band was measured by use of the Gel Documentation System. The ratio of IMD mRNA to beta-actin mRNA was considered the relative amount of IMD. When compared with control, the blood pressure increased significantly in the hypertrophy group. There was no statistically significant difference between the treatment groups. No significant difference in heart rate was noted at 4 weeks after operation in all groups. LVMI and LVTDM levels were significantly higher in the hypertrophy group than in the other groups; LVMI and LVTDM levels showed no significant difference among the treatment groups but they were obviously higher than those of the Sham-operation group. The gene expression of IMD mRNA in the hypertrophy group was upregulated in the myocardium, when compared with that in the other groups. Meanwhile, although IMD mRNA in the treament groups was higher than that in the Sham-operation group, no statistically significant difference of myocardial IMD mRNA was found between the treament groups. These results suggested that, in this experiment, intracardiac IMD mRNA was upregulated and could participate in the regulation of cardiac remodeling in renal vascular hypertension-induced cardiac hypertrophy. This upregulation could improve the pathologic and physiologic process of cardiac hypertrophy, and could associate with the pressure loading or myocardia hypertrophy. However, the change did not display any difference that could be attributed to the variety of hypotensive drugs.

Aim: To identify the expression of proteins in cardiomyocytes in rats with left kidney artery coarctation., Methods: 16 male SD rats were separated into 2 groups (n=8): 2 kidney 1 Clip group (2K1C) and sham operation group (SO). The postoperational 8th week, after examination by normal doppler and tissue doppler echocardiography, the extracted proteins from cardiomyocytes were isolated by two-dimensional gel electrophoresis with staining. The gel images were acquired by scanner and 2-DE analysis software. Different spots observed on two 2D gels were selected and identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS)., Results: Overall, 21 protein spots showed significant difference, and 14 out of which were identified., Conclusion: Kidney artery coactation-induced cardiac hypertrophy displays different expression of proteins in cardiomyocytes.

To investigate the anti-cardiac hypertrophic mechanism of statins, thirty-eight male Wistar rats were randomly allocated to four groups. Rats in model group received nitric oxide synthase inhibitor, N-nitro-L-arginine (L-NNA) 15 mg/(kg.d) by peritoneal injection. Rats in simvastatin treatment groups were given simultaneously L-NNA as those in model group and simvastatin 5 or 30 mg/(kg.d) intragastrically respectively. Rats in control group received the same volume of normal sodium. Left ventricular function, left ventricular mass index (LVMI), the content of brain natriuretic peptide (BNP) in plasma and myocardium, myocardial hydroxyproline and heme oxygenase activity were determined after 6 weeks. The results showed that rats in model group developed significant cardiac hypertrophy associated with reduced left ventricular function compared with the control group. However, compared with the model group, L-NNA-induced cardiac hypertrophy of rats was significantly relieved in simvastatin treatment groups, associated with improved left ventricular function, decreased LVMI, lower BNP levels in plasma and myocardium, lower content of myocardial hydroxyproline, and increased myocardial heme oxygenase (HO) activity. In cultured rat neonatal cardiomyocytes, simvastatin (30 or 100 mumol/L) significantly increased heme oxygenase-1 (HO-1) mRNA expression, HO activity as well as the production of CO in cardiomyocytes. Cultured with zinc protoporphyrin, a HO inhibitor, or simvastatin alone did not change [(3)H]leucine uptake of cardiomyocytes. However, cocultured with simvastatin significantly inhibited the cardiomyocyte [(3)H]leucine uptake induced by angiotensin II in a concentration-dependent manner. Cotreatment with zinc protoporphyrin significantly abolished the suppressive effect of simvastatin on cardiomyocyte [(3)H]leucine uptake. These data suggest that the activation of HO-1/CO pathway may be one of the important mechanisms by which statins inhibit cardiac hypertrophy caused by hypertension.

Objective: To investigate the effect of trans-resveratrol on hypertension-induced cardiac hypertrophy and its potential mechanisms involving endothelin (ET), angiotensin II (AngII) and nitric oxide (NO)., Methods: Animal models bearing cardiac hypertrophy were replicated in male SD rats following partially nephrectomy (PNX). 10 mg/kg bw or 50 mg/kg bw of resveratrol was administered to rats by gavage, respectively, for 4 weeks. PNX control and sham-operation control (SHAM) were simultaneously established. Systolic pressure of rats was measured through tail at baseline and it, as well as heart weight, was measured after 4-week treatment. Serum ET-1 and AngII concentrations were determined using radioimmunological assay and NO using nitric acid reductase method., Results: After 4-week treatment, animals in PNX control group had significantly higher systolic pressure and heart weight, higher ET-1 and AngII concentrations while lower NO concentrations, compared with those in SHAM group (P < 0.05). Rats treated with 50 mg/kg bw of resveratrol had significantly lower systolic pressure and heart weight, lower ET-1 concentrations while higher NO concentrations, compared with animals in PNX group (P < 0.05)., Conclusion: Trans-resveratrol could protect against the increase of systonic pressure and subsequent cardiac hypertrophy in vivo, which mechanisms might, at least partly, involve with its modulation on NO, AngII and ET.

Objective: This study is to see the pathologic change of cardiac myocyte in Athlete's Heart, and explore the mechanism of the pathologic change., Methods: Fifteen male SD rats were separated randomly into control group (without any exercise), aerobic exercise group (Ae group, swimming for 75 min every day), and overloading exercise group (Oe group, swimming for 180 min with a loading of 5 percent of body weight every day). After 5 days per week for 12 weeks, swimming stopped, the rat hearts were prepared to specimens and examined under Transmission Electron Microscope., Results: The Ae group, the number and volume of mitochondria increased, and the membrane of mitochondria remained entire. Few of dense bodies were found in cytoplasm. The nucleus envelopes of expansion nucleus appear as dentition. These changes were considered as the adaptation to exercises. At the same time, some pathologic changes of the cardiac myocytes similar to senescence also appeared, such as mitochondria expanse, the crista disorder or disappearance, unclear mitochondria membrane, many dense bodies in cytoplasm, nucleus disfiguration and chromatin collection at edge., Conclusion: After exercise training, some pathologic changes of cardiac myocyte also occur with physiological changes. With the raise of exercise intension, the pathologic changes become more obvious, even appearance of cardiac myocyte death.

Objective: To see the change of capillary of heart in Athlete's Heart, so that to discover the mechanism of pathologic change., Method: 18 male SD rats were separated randomly into control group (without any exercise), aerobic exercise group (swimming for 75 min every day), and overload group (swimming for 180 min with 5% weight of its body every day). After 5 days per week, 12 weeks, exercise training stopped and heart of rats were observed under Transmission Electron Microscope., Results: In aerobic exercise group, the capillary cavities in heart expand, the walls of capillary become thick; the number of mitochondrion increases; endothelium cells become active in growth. However, after overload exercise, the walls of capillary cockle and protuberances appear. The mitochondrion swell and the cristae become disorder. Most of endosomes expand and their number increases. The karyons become abnormity in shape and uniformity in electronic density, besides the nuclear envelope cockle. The basilar membranes become thick and unclear., Conclusion: After exercise training, both physical and pathologic changes in heart capillary are found. In suitable exercises group, the capillaries change physically; the pathologic changes are becoming visible after overload exercise however.

Objective: To assess the diagnostic value of Doppler color echocardiography for Kawasaki disease (KD) with cardiac involvement., Methods: Doppler color echocardiography was performed in 58 KD cases for measurement of the diameter of the coronary artery and the dimensions of the ventricles. The ejection fraction (EF) of the heart was also calculated and the presence of pericardial effusion and valvular regurgitation examined., Results: Cardiac involvement was identified in 31 (53.45%) of the total 58 patients, and 28 patients were found to have coronary artery lesions. Uncomplicated left and right main stem coronary artery lesions were detected in 17 and 3 patients, respectively, lesions involving both two coronary arteries in 8, coronary aneurysms in 2, left ventricle enlargement in 9, right ventricle enlargement in 6, and enlargement of the whole heart in 4 patients. Eighteen patients had mitral regurgitation, 16 had tricuspid regurgitation, 13 had pericardial effusion, and 2 developed temporary cardiac dysfunction., Conclusions: Doppler color echocardiography is capable of depicting dynamically the pathological changes and progression of the coronary artery lesions with prognostic indications, to serve as the most valuable non-invasive modality for diagnosis of KD with cardiac involvement.

To get insights into the principles of gene expression changes during cardiac hypertrophy, three rat cardiac hypertrophy models were prepared, i.e., suprarenal abdominal aortic stenosis (SRS), arterial-vein fistula (AVF) and continuous jugular vein infusion of norepinephrine (NEi). The cardiac function and structure were analyzed by echocardiograph as well as histological examination. Total RNA of left ventricles was extracted and gene expression profiles were analyzed by cDNA microarray. SRS and NEi induced concentric cardiac hypertrophy and AVF induced eccentric hypertrophy in rats, among which NEi caused obvious cardiac fibrosis. The changes of gene expression profiles were compared comprehensively across different pathologic cardiac hypertrophy models. While gene expression profiles of different cardiac hypertrophy models compared with pairs, parts of the genes involved were found overlapped, and mostly the gene expression changed in the same direction between two models, but some of them changed in the opposite directions. Expression levels of 19 genes were found changed across all cardiac hypertrophy models, and genes relatively regulated in a specific model was also found when comparison of all the three models was carried out. Novel clues for further study might derive from the results mentioned above, and some genes might be the marker genes of cardiac hypertrophy or the targets of therapy.

Objective: To study the effect of Sanhuang Jiangtang recipe (SJR) on renin-angiotensin system in local myocardium in diabetic rats., Methods: Rats were made into diabetes model by intraperitoneally administering of streptozocin, and medicated through gastrogavage with SJR (50 g/kg), gliclazide (20 mg/kg), captopril (15 mg/kg) and nitrendipine (30 mg/kg) respectively, for successive 8 weeks, started from 2 weeks after modeling. Levels of fasting blood sugar (FBS), serum insulin (Ins), heart/body weight ratio (H/BW), myocardial angiotensin II (Ang II), angiotensin converting enzyme (ACE) and aldosterone (ALD) were determined. And the mRNA expression of type I angiotensin receptor (AT1R) in myocardium were detected by RT-PCR assay., Results: As compared with those in the normal rats, levels of FBS, H/BW, Ang II, ACE, ALD and AT1R mRNA expression were higher (all P < 0.05) and level of serum Ins was lower (P < 0.01) in the model rats. SJR, gliclazide, captopril and nitrendipine could slightly reduce the blood sugar level in model rats, but with no increase of serum Ins. All the four drugs could reduce H/BW, Ang II, ACE and AT1R mRNA expression. SJR and captopril could also decrease the ALD content in myocardium., Conclusion: Cardiac hypertrophy has been induced in 10 weeks after diabetic modeling. Activation of local myocardial RAS is related to the genesis of diabetic cardiomyopathy. SJR, gliclazide, captopril and nitrendipine could antagonize the genesis of diabetic cardiomyopathy, the mechanism is related to the inhibition of RAS activation in local myocardium.

Pressure overload can result in heart hypertrophy, and induce apoptosis, but the phenomenon of apoptosis during the forepart of cardiomyocyte hypertrophy remains unclear. The aim of this study was to inquire into the process of cardiomyocyte apoptosis during the forepart of cardiomyocyte hypertrophy. We constructed the hypertrophy model by transverse aortic constriction of male SD rat. The apoptosis ratio was detected by TUNEL method and FCM. The result demonstrated that hypertrophy indexes increased with the time of constriction, reached the highest level at day 7, maintained that level, and then decreased at day 91. The apoptosis ratio of cardiomyocyte at day 4 was higher than that at day 0 detected by FCM method, and the ratio at day 7 was markedly lower than that at day 4. After day 28, the apoptosis ratio of cardiomyocyte went up again with the time of constriction after surgery. TUNEL method revealed that positive nuclei were observed in cardiomyocytes exclusively in the left ventricle; the apoptosis ratio increased when constriction continued. TUNEL method confirmed the result of FCM. These data indicate that cardiac hypertrophy is initiated by apoptosis of cardiomyocyte, these two factors(hypertrophy and apoptosis) maintain the balance between growth and death during the early short period of aortic constriction, and when aortic constriction goes on they are involved in the pathogenesis of heart remodeling.

The aim of this study was to determine the regulation by MKP-1 of MAPK activity and protein expression in cardiomyocyte hypertrophic response induced by Ang II. Neonatal rat cardiomyocyte hypertrophic response was assayed by cell surface area, protein synthesis rate and protein content. MAPK activity was determined by an in-gel kinase assay. Protein expression of MAPK and MKP-1 were detected by Western blotting. The results are as follows. (1) Ang II induced promotion of (3)H-leucine incorporation and increase in cell protein content and cell surface area in a dose-dependent manner. Pretreatment with a selective AT(1) receptor antagonist CV11974 or a specific MEK inhibitor PD098059, cardiomyocyte hypertrophic response induced by Ang II was inhibited by 85% and 32.5%, respectively. (2) After pretreatment with PD098059 or CV11974, AngII-induced increases in p44MAPK and p42MAPK protein expression and enzyme activity (expressed by gamma-(32)P-ATP incorporation) were all inhibited obviously. (3) With treatment of myocytes by Ang II for 5 min, MAPK activity determined by p44MAPK and p42MAPK protein expression began to increase, while MKP-1 protein expression was detected within 30 min and lasted more than 2 h following treatment with Ang II. (4) Pretreatment of cardiomyocytes with actinomycin D (3 microgram/ml) for 30 min inhibited MKP-1 protein expression, while p44MAPK and p42MAPK protein expression was still detected 120 min after Ang II treatment. The above results demonstrate that activation of MAPK plays an important role in Ang II-induced cardiomyocyte hypertrophic response in neonatal rat cardiomyocytes through MKP-1 mediated inactivation of p44MAPK and p42MAPK.cardiomyocyte hypertrophic response in neonatal rat cardiomyocytes through MKP-1 mediated inactivation of p44MAPK and p42MAPK.

In order to investigate the relationship between cAMP and myocardial renin-angiotensin system activation after acute pressure overload, an animal model of acute pressure overload was established by constriction of abdominal aorta. It was found that angiotensin converting enzyme (ACE) mRNA and protein expression were increased markedly, ACE activity and angiotensin II content were also elevated significantly in rat heart 1 h after acute pressure overload, and the increases were kept at high level. Meanwhile the myocardial cAMP concentration was increased significantly at 0.5 h, reached the peak at day 5, and returned to normal at day 30 after operation. Then cardiomyocytes were cultured to observe whether ACE gene expression can be induced by cAMP. The results showed that elevation of cAMP content in cultured cardiomyocytes stimulated by isoproterenol (ISO, 0.01 micromol/L) increased ACE mRNA and protein expression, and also increased ACE activity and Ang II content in cultural medium. These results suggest that cAMP plays a role in the mechanism of activation of myocardial renin-angiotensin system induced by pressure overload.

The present work demonstrated that cultured neonatal rat ventricular fibroblast conditioned growth medium (FCGM) could significantly increase cell surface area and protein content and promote (3)H -Leucine incorporation on neonatal rat cardiomyocyte. The above effect was strongest on the third day, and was dose-dependent. BQ(123), an ET-A receptor antagonist, significantly blocked the effect, while CV11974, an Ang II I-type receptor antagonist, and regitin, an alpha-adrenergic receptor antagonist, did not. These results suggest that there are some substances promoting hypertrophy of cardiomyocytes in FCGM, which may be ET-1. The FCGM-induced increases in cardiomyocyte protein synthesis and cell surface area were inhibited partially by pertusis toxin (PTX) and PKC inhibitor staurosporine (ST), suggesting that the hypertrophic effect is related with PTX sensitive G protein and PKC.

Mitogen-activated protein kinases (MAPKs) are thought to be critical components in signal transduction pathways in regulation of cell growth and differentiation. The purpose of the present investigation is to study possible involvement of MAPKs in the progress of cardiac hypertrophy in spontaneously hypertensive rats (SHRs) and effects of age on Angiotensin II (Ang II), MAPK activity and cardiac hypertrophy. The animals were divided into three groups: 4 months old WKY rats (n = 8), 4 month old SHRs (n = 8) and 15 month old SHRs (n = 6). Ratio of heart to body weight was measured. Ang II was determined by RIA. MAPK activity in cardiac tissue was assayed by the "in-gel" myelin basic protein phosphorylation. The results show that in comparison with 4 month old WKY rats, Ang II in plasma and cardiac tissues were elevated (216.4%, P < 0.01; 101.2%, P < 0.01) in 4 months old SHRs, while the MAPK activity was increased 107.0% (P < 0.01) with a parallel cardiac hypertrophy (P < 0.01). In comparison with 4 month old SHRs, Ang II and MAPK activity in cardiac tissue of the 15 months old SHRs were decreased (31.3%, P < 0.01; 29.7%, P < 0.05) but the cardiac hypertrophy increased by 38.5% (P < 0.01). MAPK may be involved in the progress of cardiac hypetrophy in SHR and the increased MAPK activity may be partly induced by Ang II.

Our previous studies have shown that the myocardial phenotypes between exercise-induced and hypertensive cardiac hypertrophy are different. However, alteration of cardiac gene expression in the two kinds of hypertrophy is not clear. We therefore studied the expression of immediate early and late responsive gene in Wistar rats subject to a 12-weeks swimming program and spontaneously hypertensive rats (SHR) by Northern blot. The autoradiographs were analyzed by scanning densitometry. When compared with matched sedentary control, swimming rats and SHR increased their heart/body weight by 29% and 61% respectively (P < 0.01). After a series of swimming program, levels of c-fos and atrial natriuretic factor (ANF) mRNA were instantly increased 203% and 214% respectively in the swimming rats. However in 24 h after swimming, ANF mRNA was decreased to the level of control but c-fos mRNA was still higher than than in control. The levels of c-fos and ANF mRNA were increased by 80% and 298% in SHR respectively. The expression of beta-myosin heavy chain (MHC) mRNA was increased by 117% in SHR but decreased by 12% in swimming rats. The expression of alpha-MHC mRNA was decreased by 42% in SHR but unchanged in swimming rats. The abundance alpha/beta-MHC mRNA in swimming rats is 336% higher than in SHR. These results showed differential expression of the immediate early and late responsive gene in exercise-induced and SHR hypertrophied heart remodeling. It is suggested that (1) the differential expression of c-fos gene may differently regulate remodeling of these two cardiac hypertrophies; (2) the differential expression of ANF gene may be a molecular marker for distinguishing the two kinds of cardiac hypertrophy; and (3) the differential expression of alpha/beta-MHC gene ratio may regulate exercise-induced and hypertensive hypertrophied myocardial cell changing to contractile phenotype and synthetic phenotype respectively, at the gene transcription level.

Whether oxygen free radicals (OFRs) are involved in the development of myocardial hypertrophy was studied. After 3 months of abdominal aorta banding in rats, an increase in myocardial lipid peroxide (LPO) content, a decrease in superoxide dismutase (SOD) activity and an increment in myocardial mass occurred. Heart weight/body weight, left ventricular weight/body weight and left ventricular wet weight/dry weight showed positive correlations with myocardial LPO content (r = 0.6604, 0.6939 and 0.6835, P < 0.05) and negative correlations with myocardial SOD activity (r = -0.6841, -0.6540, and -0.6022, P < 0.05). OFRs scavenger SOD, given to the aorta banding rats for 1 month, inhibited the evolution of cardiac hypertrophy, decreased myocardial LPO content and elevated SOD activity. These results indicated that OFRs are most likely involved in the development of myocardial hypertrophy, which may be antagonized or prevented by OFRs scavenger SOD.

To explore the possible relationship between acute viral myocarditis and dilated cardiomyopathy (DCM), 35 acute diffuse viral myocarditis (ADVM) patients with cardiac enlargement were studied for 6 years on average. The results showed that: (1) In 22 ADVM patients, the dilated hearts had returned to normal on X-ray films. The other 13 cases still had cardiac enlargement complicated with various degrees of cardiac insufficiency (NYHA II/III) and ECG abnormalities. The manifestation of these 13 patients resembled those seen in the early stage of DCM. (2) Serum neutralizing antibody titres of Coxsackie B virus (CBV) in 35 ADVM patients after 6 years observation on average were significantly higher than those cases with cardiac enlargement induced by other causes (P less than 0.01). High neutralizing antibody titres (greater than or equal to 320) to CBV were more common among the patients with ADVM 65.7% vs 25.7% (P less than 0.05). The results indicate that some cases of ADVM might develop into DCM.

Either chronic hypoxia or polycythemia induced by CoCl2 injection resulted in an increase of RBC, Hb, Hct and blood viscosity at different shear rate. There was an increase of right ventricular systolic and end diastolic pressure, +/- dp/dtmax, Vmax and right weight index, as compared with the control rats. Chronic hypoxia combined with polycythemia induced by CoCl2 injection further augmented the above parameters except Vmax of RV, and caused an increase of left ventricular weight index. The positive correlation was seen between the RV weight index and Hct. The above results prove that polycythemia might play important role in pathogenesis of hypoxic myocardial hypertrophy.

Thirty hypertensive patients with increased left ventricular (LV) mass and impaired diastolic function received routinely 2 or 3 kinds of captopril, nifedipine and atenolol for a mean period of 98 days. The LV mass index (LVMI) decreased by an average of 21 g/M2, but no significant correlation between blood pressure reduction and decrease in LVMI was found. So there may be some direct effect of these antihypertensive agents on the myocardium in addition to the benefit from blood pressure reduction. Marked reduction in PVA, Ai, A/E and Ai/T-VTi (P less than 0.01) along with elevation in ratio of E/A, Ei/Ai and Ei/T-VTi (P less than 0.01) were also observed by Doppler transmitral filling studies. These results indicated that the impaired LV diastolic function in patients with hypertension can be much improved following reduction of blood pressure and LV mass.

Renovascular hypertension was induced in rats by left renal artery constriction. Force-velocity relation, end systolic tension-length relation (ESTLR) and responses to high extracellular calcium were investigated in hypertrophied myocardium with 4-week hypertension. The results showed that: (1) The myocardial hypertrophy was accompanied by increased peak active tension, decreased maximal velocity of shortening and prolonged contraction duration (P less than 0.01). (2) The ESTLR in hypertrophied myocardium was similar to that in the control, fitted well by an exponential curve and did not show significant alterations in all its regression parameters (P greater than 0.05). (3) No significant difference about the responses to high extracellular calcium (4 mmol/L) was observed between the control and the hypertrophied myocardium (P greater than 0.05). It is concluded that the mechanical properties of hypertrophied myocardium were characterized by a dissociation between force development and velocity of shortening and possibly these contractile abnormalities at the early stage of cardiac hypertrophy are not related to ability of calcium transport in cardiac plasma membrane. The indexes of myocardial mechanics are more sensitive to changes in contractility of hypertrophied myocardium as compared with the parameters of ESTLR.

A study which enrolled 65 middle-aged and elderly essential hypertensive patients with Kidney-deficiency pattern was carried out to evaluate the effects of Longevity-Antihypertensive-Mixture (LAM). As LAM was composed of Kidney-tonifying herbs, all the subjects chosen fell into the pattern of Kidney-deficiency in TCM. The subjects were randomized into two groups: The LAM group had 34, and the control group taking Apocyhum Venetum L. Fluid (AVLF) 31. The duration of medication was 12 weeks. The main results were as follows: (1) At the end of week 4, the supine systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) in LAM group declined from 171 +/- 16 (mmHg, the same below), 101 +/- 6 and 127 +/- 7 to 153 +/- 12, 93 +/- 7 and 113 +/- 7 respectively. At the end of week 12, the supine SBP, DBP and MBP were 151 +/- 14, 93 +/- 6 and 112 +/- 8. There was significance of difference in the reduction of supine blood pressure compared with baseline (P less than 0.001). AVLF produced similar changes in the reduction of supine SBP, DBP and MBP. However, the magnitude of reduction in SBP and MBP was smaller than those with LAM (P less than 0.001). (2) There was no significance of difference in attaining goal blood pressure between LAM and AVLF groups (P greater than 0.05). At the end of week 4, 79.41% and 77.42% were achieved respectively; at 12, 79.41% and 80.65%. (3) LAM had stronger effect on relieving symptoms of essential hypertension and Kidney-deficiency than AVLF (P less than 0.05). (4) In LAM group the left ventricular mass index (VMI) decreased from 114.75 +/- 42.40 g/m2 to 100.39 +/- 36.08 g/m2 (P less than 0.001). The LVMI in AVLF group increased from 117.27 +/- 36.90 g/m2 to 117.68 +/- 38.37 g/m2 (P greater than 0.05). The results supported the therapeutic principle of TCM: Treating patients according to their pathophysiological patterns.

The FEV1/FVC was less than 60 per cent in all of our COPD patients. Their 3-year, 5-year and 7-year survival rate was 64.7%, 49.1% and 34.1% respectively. The 7-year survival rate in FEV1 greater than 1.0L, 0.75-1.0L and less than 0.75L group was 58.1%, 40.7% and 14.1% separately. Other factors contributed to the poor prognosis of COPD were: hypoxemia, tachycardia, right ventricular hypertrophy etc.

104 patients of hypertensive left ventricular hypertrophy (LVH) were studied by two-dimensional echocardiography. According to the changes of left ventricular wall thickness, wall mass, end-diastolic volume and ejection fraction, they were divided into three types (concentric, dilated, disproportionate): (1) Concentric LVH 83 cases (79.8%) with thickened ventricular wall and augmented mass. (2) Dilated LVH 13 cases (12.5%) with left ventricular cavity enlarged and both ventricular mass and volume increased, ejection fraction decreased. (3) Disproportionate LVH 8 cases (7.7%), similar to hypertrophic cardiomyopathy with excess increase in interventricular septal thickness. The thickness ratio between interventricular septal and left ventricular posterior wall was greater than or equal to 1.3.