Effects of cardiac contractility modulation on ventricular electrical remodeling in rabbits with chronic heart failure

AIM: To investigate the effects of cardiac contractility modulation (CCM) on ventricular electrical remodeling in a rabbit model of chronic heart failure. METHODS: The rabbits were divided into sham group, heart failure(HF) group and HF+ CCM group. The rabbit model of chronic heart failure was established by ligating the ascending aortic root. Then electrical stimulations during the absolute refractory period were delivered lasting 6 h everyday for 4 weeks in rabbits of HF+ CCM group. The QTc and ventricular effective refrective period (VERP) were recorded. The protein and mRNA levels of Kv1.4, Kv4.3 and connexin 43 (Cx43) were determined by Western blot and RT-qPCR. RESULTS: Compared with sham group, QTc were significantly prolonged in HF rabbits at week 12 (P<0.05). CCM therapy shortened QTc of rabbits with heart failure at week 16 (P<0.05). Compared with sham group, VERP significantly increased in HF group and HF+ CCM group, while CCM therapy shortened VERP of rabbits with heart failure at week 16 (P<0.05). Compared with sham group, the mRNA and protein levels of Kv1.4, Kv4.3 and Cx43 were decreased in HF group and HF+ CCM group (P<0.05). However, CCM therapy restored the mRNA and protein levels of Kv1.4, Kv4.3 and Cx43 of rabbits with heart failure (P<0.05). CONCLUSION: CCM suppresses ventricular electrical remodeling in heart failure and the underlying mechanism may be associated with increasing Kv1.4, Kv4.3 and Cx43 expression.     

Downregulated transient outward potassium channel protein Kv4.2 and Kv4.3 expression in PVN contributes to sympathoexcitation in rats with chronic heart failure

AIM: To investigate the transient outward potassium channel protein expression in paraventricular nucleus(PVN) and its contribution to renal sympathetic nerve activity(RSNA) in rats with chronic heart failure(CHF).METHODS: A rat model of CHF was prepared by acute myocardial infarction that was induced by ligation of the left anterior descending coronary artery. Four weeks after heart failure, echocardiogram was applied to identify the CHF model and plasma norepinephrine(NE), serum NH₂-terminal pro-brain natriuretic peptide(NT-proBNP) were detected by ELISA. The expression of ransient outward potassium channel proteins Kv4.2 and Kv4.3 at mRNA and protein levels was determined by real-time PCR and Western blot. The mean arterial pressure(MAP), heart rate(HR) and RSNA were measured in anesthetized rats with PVN microinjection of potassium channel blockers 4-AP. RESULTS: In CHF group, the rat cardiac function and Kv4.2 and Kv4.3 expression in PVN were obviously lower while plasma NE and serum NT-proBNP were obviously higher than those in sham group. Microinjection of 4-AP into PVN induced an increase in MAP, HR and RSNA in both sham and CHF rats, while the CHF rats exhibited smaller responses to 4-AP than sham-operated rats.CONCLUSION: Downregulation of Kv4.2 and Kv4.3 expression in the PVN may be a potential mechanism for sympathoexciation in the rats with chronic heart failure.     

Effect of spironolactone on hyperthyroxine-induced atrial fibrillation and atrial remodeling in rabbits

AIM: To detect the effect of spironolactone on hyperthyroxine-induced atrial remodeling. METHODS: New Zealand rabbits were divided into control group (C), hyperthyroxine group (H) and spironolactone group (S). Thyroxin was given to the rabbits in group H and group S by intraperitoneal injection for 4 weeks, and then spironolactone was given in group S by gavage for 2 weeks. Atrial fibrillation (AF) was induced by "burst" stimulation after administration. The inducing rate of AF and atrial effective refractory period (AERP) were tested by intra-cardiac electrophysiologic instrument. The expression of AF-related Ca²⁺ channel (Cav1.2), K⁺ channels (Kv1.5 and Kv4.3) and connexins (Cx40 and Cx43) at mRNA and protein levels was detected by real-time PCR, immunohistochemistry and Western blot. RESULTS: Spironolactone reduced the inducing rate of AF. No significant difference of AERP between group H and group S was observed (CONCLUSION: Spironolactone attenuates the hyperthyroxine-induced atrial remodeling in rabbits, and reduces the susceptibility of the myocardium to AF.     

Effects of atorvastatin on atrial electrical remodeling in a rabbit model of chronic atrial fibrillation

AIM: To evaluate the effects of atorvastatin (ATO) on atrial electrical remodeling in a rabbit mo-del of chronic atrial fibrillation (AF) produced by 3 weeks of rapid atrial pacing (RAP). METHODS: The sternotomy was performed and the pacing and testing electrodes were fixed to the left atria of 24 New Zealand white rabbits. The animals were randomly divided into 3 groups. The rabbits in model group and ATO group were subjected to RAP for 3 weeks, and then were treated with placebo and ATO (2.5 mg·kg^-1·d^-1), respectively. The rabbits in sham group did not receive RAP and drugs. Electrophysiological examination was performed to test heart rate, P-wave duration, atrial effective refractory period (AERP) and AF inducibility. The protein expression levels of Cav1.2, Kv4.3 and myeloperoxidase (MPO) were detected by Western blot. RESULTS: Sustained AF was induced in 5 and 4 rabbilts in model group and atorvastatin group and no rabbits in sham group was found. After 3 weeks of RAP, compared with sham group, heart rate and P-wave duration were increased and AERP was shortened in model group and ATO group (P<0.05). Compared with model group, AERP was increased in ATO group (P<0.05), while heart rate and P-wave duration had no difference between these 2 groups. Compared with sham group, the protein levels of Cav1.2 and Kv4.3 were decreased, and protein level of MPO was increased in model group and ATO group (P<0.05). Compared with model group, Cav1.2 was increased and MPO was decreased in ATO group (P<0.05), while Kv4.3 had no difference between these 2 groups. CONCLUSION: Atorvastatin suppresses the down-regulation of atrial Cav1.2 protein level and the shortening of AERP, thus preventing atrial electrical remodeling in a rabbit model of chronic AF. The effect of atrovastatin on reducing atrial MPO level may be the potential mechanism.     

Effect of angelica on myocardial fibrosis post myocardial infarction in rats

AIM: To investigate 1) the role of transforming growth factor-β₁ (TGF-β₁) and macrophage infiltration during the development of myocardial fibrosis (MF) in rats after myocardial infarction (MI);and 2) mechanisms of MF post-MI and the inhibitory effect of angelica.METHODS: Sprague-Dawley (SD) rats were subjected to MI by ligating the left anterior descending coronary artery.The animals were randomly divided into three groups: sham, MI and MI+angelica.After 24 hours of ligation, rats received angelica (20 mL·kg^-1·d^-1, ip) or saline.Left ventricular hemodynamics were measured and rats were killed at week 1, week 2 and week 4, respectively.Collagen content, macrophage infiltration and TGF-β₁ expression were examined in the non-infarcted area.RESULTS: ① In MI group, the numbers of macrophage and TGF-β₁ expression were significantly upregulated compared to sham at week 1 post-MI and remained elevated at week 4 (P<0.01).Angelica significantly decreased macrophage infiltration and TGF-β₁ expression (P<0.01 vs MI).② Collagen content was increased significantly in MI group compared to sham at week 2 and week 4 (P<0.01), and decreased in MI+angelica group (P<0.05 vs MI).③ Cardiac function was markedly decreased post-MI in MI group (P<0.01), and improved at week 4 in MI+angelica group (P<0.05).CONCLUSION: In MF post-MI, angelica may have an antifibrotic effect by decreasing macrophage infiltration and TGF-β₁ expression, by which reactive myocardial fibrosis is reduced, and cardiac function is improved.     

Effects of non-excitatory electric stimulation on cardiac function in normal and infarcted heart rabbits and it's regional effect on myocardium

AIM: To investigate the influences of electric stimulation applied during the absolute refractory period (ARP) on the cardiac function of normal rabbits and rabbits after myocardial infarction (MI) and to observe the regional effects of this electric stimulation. METHODS: 64 rabbits were randomly assigned to normal and MI groups and each group was then divided into the anterior and posterior groups. A thoracotomy was performed 4 weeks after MI in rabbits. One set of electrodes was inserted into the anterior and posterior wall of left ventricle of the anterior and posterior groups, respectively. Current pulses were delivered during the ARP (called CCM) during sinus rhythm in rabbits. The left ventricular systolic pressure (LVSP) and the left ventricular end diastolic pressure(LVEDP) as well as maximum positive and negative left ventricular pressure change (±dp/dt_max) were observed. RESULTS: In the normal and MI groups, LVSP, +dp/dt_max significantly increased, and LVEDP, -dp/dt_max were reduced during CCM stimulation compared with the baseline (P<0.05). In the normal rabbits, electric stimulation in the anterior group improved the cardiac function more significantly than that in the posterior group (P<0.05). In the MI rabbits, there was no difference between the anterior and the posterior groups (P>0.05). CONCLUSION: Electric stimulation delivered during the ARP significantly enhances the contractility and the relaxation of myocardium in normal rabbits and rabbits after MI, and the effects of CCM stimulation on heart are regional.     

Quercetin inhibits inflammasome activation in diabetic rats and attenuates myocardial injury

AIM:To observed the effect of quercetin on NLRP3 inflammasome activation in the rats with diabetic cardiomyopathy (DCM) and its protective effect on the myocardium. METHODS:Male SD rats (n=40) were randomly divided into normal control group (n=10) and model group (n=30). The rats in model group were intraperitoneally injected with streptozotocin at 60 mg/kg to establish the model of diabetes mellitus (DM). Blood glucose was measured weekly. After 4 weeks, the rats with random blood glucose ≥ 16.6 mmol/L were selected as DM animals. The rats with DM were randomly divided into 3 groups:DM group, DM+vehicle group and DM+quercetin group. The rats in DM+quercetin group were intragastric infusion with quercetin at 100 mg/kg per day. The cardiac function was measured at the end of the 16th week. The methods of Masson staining and HE staining were used to observe the morphological changes of the myocardial tissues. Western blot, ELISA and immunohistochemistry were used to observe the changes of NLRP3, ASC, caspase-1, interleukin (IL)-1β and IL-18. TUNEL staining was used to observe myocardial apoptosis. RESULTS:Quercetin significantly inhibited the activation of NLRP3 inflammasome in the myocardium of the DM rats (P<0.05). The levels of IL-1β and IL-18 in DM+quercetin group were significantly decreased, quercetin reduced cardiac tissue apoptosis, and the cardiac function in DM+quercetin group was significantly improved (P<0.05) compared with DM group and DM+vehicle grpup. CONCLUSION:Quercetin significantly inhibits the activation of NLRP3 inflammasome, and reduces the levels of inflammation and myocardial apoptosis, thus protecting the heart function of DCM rats.     

Role of Kv1.3 channel of CD4+T lymphocytes in the formation of atherosclerosis in rat spleen

AIM: To investigate the function of voltage-gated potassium channel Kv1.3 and its possible role in CD4⁺ T lymphocytes in the formation of atherosclerosis (AS) in rat spleen. METHODS: The rat atherosclerosis model was established by feeding high-fat diet. The proportion of lymphocytes was determined by flow cytometry. The CD4⁺ T lymphocytes were separated using immunomagnetic bead. The mRNA expression of Kv1.3 in CD4⁺ T lymphocytes was detected. The concentrations of intracellular calcium and cytokines were also measured. RESULTS: (1) The proportion of CD4⁺ T lymphocytes in AS group was significantly higher than that in control group (74.93%±2.15% vs 67.80%±2.54%, P<0.05). (2) After stimulated with concanavalin A (ConA), the proliferation of CD4⁺ T lymphocytes in AS group was significantly higher than that in control group (1.1321±0.1750 vs 0.7971±0.0955, P<0.05). (3) After stimulated with ConA, the concentration of intracellular calcium in AS group was higher than that in control group. (4) In AS group, the releases of cytokines of IL-2 and TNF-α in AS group were significantly higher when stimulated with ConA for 48 h than that for 24 h. (5) The mRNA expression of Kv1.3 in CD4⁺ T lymphocytes was greatly higher in AS group than that in control group (3.670±1.579 vs 1). CONCLUSION: In AS rats, the increase in CD4⁺ T lymphocytes as well as the augmentation of Kv1.3 mRNA expression in the cells suggest that up-regulation of Kv1.3 mRNA expression in CD4⁺ T lymphocytes may be involved in the mechanism of atherosclerotic formation in rat spleen.     

Dynamic expression of S-adenosyl-L-homocysteine hydrolase under intervention of fimasartan in early stage of type 2 diabetic cardiomyopathy rats

AIM: To detect the changes of S-adenosyl-L-homocysteine hydrolase (SAHH) signaling pathway and related proteins under the intervention of fimasartan (FIM) in rats with diabetes mellitus (DM), and to explore the pathological mechanism of the occurrence and development of diabetic cardiomyopathy (DCM). METHODS: The type 2 diabetic rat model was established by injection of streptozocin after 5-week high-fat diet. The rats were randomly divided into control group, DM group, and DM+FIM group. Fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and fasting insulin (FINS) levels were tested. M-mode echocardiography was performed for determining the heart functions. High-performance liquid chromatography (HPLC) was used to detect homocysteine (Hcy), S-adenosylmethionine (SAM) and S-adenosyl-L-homocysteine (SAH). The alteration of SAHH in myocardium was determined by Western blot. RESULTS: The success rate of type 2 diabetic rat modeling was 84%. Compared with DM group, the body weight of the rats in DM+FIM group increased significantly (P<0.05), while cardiac index, left ventricular index, FBG and LDL-C were significantly reduced (P<0.05). The results of echocardiography showed that ejection fraction increased (P<0.05) in DM+FIM group. HPLC detection showed that the level of Hcy and the ratio of SAM/SAH were significantly reduced (P<0.05). The results of Western blot showed that the expression of SAHH in DM group was increased compared with control group, while that in DM+FIM group declined (P<0.01). CONCLUSION: The expression of SAHH, Hcy and other related factors may be important during the occurrence and development of early DCM, and FIM may play a role in this process as an inhibitor of SAHH.     

Aerobic exercise protects cardiac function of T2DM mice by activation of PI3K (p110α)/Akt signaling pathway

AIM: To study the protective effect of aerobic exercise on cardiac dysfunction in mice and its mechanism, and to provide theoretical and practical basis for the exercise therapy of diabetic cardiac dysfunction.METHODS: The mice were divided into normal control non-exercise (NNC) group, normal control exercise (ENC) group, diabetic non-exercise (NDM) group and diabetic exercise (EDM) group. At the end of the experiment, the cardiac function was evaluated by echocardiography. The pathological changes of the myocardial tissues and the development of fibrosis were observed. The mRNA expression of ANP, and the protein levels of PI3K (p110α) and Akt were determined. RESULTS: The decrease in cardiac function of diabetic mice was observed, and the cardiac function recovered after exercise intervention (P<0.05). Under light microscope with HE and Masson staining, the myocardial structure in NDM group was in extreme disorder, cell arrangement was not neat, and the degree of fibrosis increased, but the myocardial damage was improved in ENC group. Compared with NNC group, the mRNA expression of ANP in the myocardium of diabetic mice was up-regulated (P<0.05). The protein levels of PI3K (p110α) and Akt were decreased (P<0.05), and the cascade was inactivated. Compared with NDM group, the mRNA expression of ANP was down-regulated and the protein levels of PI3K (p110α) and Akt were up-regulated in EDM group (P<0.05). CONCLUSION: Diabetes results in myocardial damage in mice, and reduces cardiac function. Exercise intervention alleviates the heart dysfunction induced by high glucose via activating PI3K(p110α)/Akt signaling pathway to protect the structure and function of the myocardium.     

Protective role of carnosine on cardiac dysfunction in type 1 diabetes mellitus rat model

AIM:To explore the effects of carnosine (CAR) on cardiac dysfunction in type 1 diabetic mellitus rats and the underlying mechanism. METHODS:The SD rats were randomly divided into 4 groups:control (C) group, control+carnosine (C+CAR) group, diabetes mellitus (DM) group and diabetes mellitus+carnosine (DM+CAR) group (n=10). The rats were sacrificed after 12 weeks. The cardiac function was assessed by ventricular cannulation. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were assessed by ELISA. The mRNA levels of tumor necrosis factor α(TNF-α), interleukin-1β(IL-1β) and IL-6 were measured by real-time PCR. The distribution of connexin 43 (Cx43) was examined by immunofluorescence. The protein levels of Cx43 and protein kinase C (PKC) were determined by Western blot. RESULTS:Compared with the C group, the left ventricular end diastolic pressure (LVEDP) was increased whereas the left ventricular pressure maximum rise/fall velocity (±dp/dt_max) was decreased in the DM group (P<0.01). The activity of SOD decreased while the MDA increased in the left ventricular tissues (P<0.01). The mRNA levels of TNF-α, IL-1β and IL-6 were increased (P<0.01). The Cx43 distribution was irregular. The protein levels of phosphorylated Cx43 and PKCε were elevated (P<0.01). Compared with the DM group, the cardiac function of LVEDP and ±dp/dt_max in DM+CAR group was ameliorated (P<0.01), with increased SOD activity and decreased MDA content (P<0.05). The mRNA levels of TNF-α, IL-1β and IL-6 were reduced (P<0.01). The Cx43 distribution was improved and the protein levels of phosphorylated Cx43 and PKCε were decreased (P<0.01). CONCLUSION:CAR treatment can improve the cardiac function by its anti-oxidative and anti-inflammation effects and suppression of Cx43 abnormalities through PKCε in DM rats.     

Synergistic effect of hypertension and type 2 diabetes on cardiac dysfunction and myocardial remodeling in mice

AIM: To investigate whether the effect of hypertension combined with diabetic can lead to cardiac dysfunction and myocardial remodeling in mice. METHODS: The diabetic mice and non-diabetic mice of 14 weeks old were administered with PBS or angiotensin II (Ang II) for 4 weeks to induce mild hypertension. The left ventricular (LV) function was assessed by echocardiography and dobutamine stress test. The LV tissues were subjected to HE staining to assess cardiac hypertrophy. The phospharylated adenosine monophosphate-activated protein kinase (p-AMPK) levels in the LV tissues were determined by Western blotting. RESULTS: Compared with control group, diabetic mice (DM group) neither displayed marked cardiac dysfunction nor myocardial remodeling. Ang II treatment did not affect body weight and glucose level, but the blood pressure was increased in the diabetic and control mice. Ang II-induced LV hypertrophy in diabetic mice was significantly higher than that in control mice as assessed by LV masses and cardiomyocyte sizes. Moreover, Ang II-treatment reduced LV fractional shortening and contractility in the diabetic mice, but not in the control mice. The p-AMPK levels were significantly reduced in Ang II group, DM group and DM+Ang II group. CONCLUSION: The cardiac function and cardiac structure of type 2 diabetic mice did not obviously change. Cardiac dysfunction and myocardial remodeling were easily induced in type 2 diabetic mice when hypertension happened, suggesting that hypertension is a critical factor of cardiac dysfunction and myocardial remodeling in type 2 diabetic mice.     

Comparison between mobilization and transplantation of bone marrow stem cells for the therapy of myocardial infarction in rabbits

AIM: To compare bone marrow stem cell mobilization with bone marrow-derived mononuclear cells (BMCs) transplantation for the therapy of myocardial infarction (MI) in rabbits, and to explore more effective and practical stem cell therapeutic strategy for MI. METHODS: In mobilization group (M, n=10), granulocyte-colony stimulating factor (G-CSF) (30 μg·kg-1·d-1) was injected subcutaneously 3 hours after MI and every 24 hours for 5 days. On the 5th day, the BMCs from 10 mL peripheral blood were labeled with bromodeoxyuridine (BrdU) for 24-48 hours, then reinjected intravenously. In transplantation group (T, n=10), BMCs transplantation was performed 5-7 days after MI. After being obtained from bone marrow (3-5 mL) of iliac crest and labeled with BrdU for 24-48 hours, BMCs were transplanted into infracted myocardium through intramyocardial injection. Control animals (C, n=10) did not receive any treatment after MI. Echocardiography were performed for the evaluation of cardiac function 1 week and 5 weeks after MI. Hemodynamic studies and histological study were performed 5 weeks after MI. RESULTS: LV ejection fraction increased significantly in group M, had no change in group T, and decreased 1 week and 5 weeks after MI in group C. Group M and group T had higher LV max +dp/dt and max -dp/dt, lower LV end-diastolic pressure compared with group C 5 weeks after MI. Histological studies revealed that there were BrdU positive cells in the infarcted area in group M and group T. The vascular density of group M and group T in the infarcted area was significantly greater in comparison with group C. No regeneration of smooth muscle cells and cardiomyocytes were found in the infarcted area. CONCLUSION: Bone marrow stem cell mobilization with G-CSF and transplantation of BMCs both significantly improve the cardiac function for the therapy of MI through vascular genesis in the infarcted area. Bone marrow stem cell mobilization may offer a new and non-invasive therapeutic strategy for MI.     

Effects of combination treatment with perindopril and losartan on left ventricular remodeling and cardiac function in patients with myocardial infarction

AIM: Inhibiting the renin-angiotensin-aldosterone system prevents left ventricular (LV) remodeling after myocardial infarction (MI). This study was designed to assess the effects of a combination of perindopril and losartan on LV remodeling, cardiac function and serum procollagen type Ⅲ aminoterminal peptide (PⅢNP) levels in patients with acute MI.METHODS: Patients with anterior MI were divided into 3 groups: MI+perindopril, MI+losartan, and MI+perindopril+losartan. After successful intervention therapy, perindopril 2-4 mg/d or losartan potassium 25-50 mg/d or combination of the both were administered. All patients took aspirin, clopidogrel and statins, while some of the patients were treated with beta-blockers, nitrate and a platelet glycoprotein IIb/Ⅲa receptor antagonist. Three months later, LV dimensions and LV ejection fraction (LVEF) were measured by ultrasonography. Plasma brain natriuretic peptide (BNP), serum C-reactive protein (CRP) and PⅢNP levels were evaluated with ELISA or RIA.RESULTS: Baseline characteristics of the 3 groups were the same. All patients showed decreased CRP, increased BNP and PⅢNP levels, and LV dilation and dysfunction after treatment for three months. Compared with the 2 single therapy groups, patients in the combination group showed significantly lower CRP, BNP and PⅢNP levels, less LV dilation and higher LVEF. Serum PⅢNP level was positively correlated with CRP level and LV end-diastolic volume index(r=0.597 and r=0.543, respectively,both P<0.01), and negatively correlated with LVEF(r=-0.565, P<0.01).CONCLUSION: For patients with AMI, combination of perindopril and losartan significantly inhibited LV remodeling and improved LV function. Inhibition of myocardial interstitial fibrosis might be part of the mechanism.     

Transplantation of bcl-2 gene-modified bone marrow mesenchymal stem cells improves cardiac function and angiogenesis in rabbit ischemic car-diac insufficiency model

AIM: To investigate the effects of transplantation of bone marrow mesenchymal stem cells (BMSCs) modified by bcl-2 gene on myocardial cell apoptosis, angiogenesis and cardiac function in the rabbit after acute myocardial infarction (MI).METHODS: The rabbit BMSCs were isolated, cultured and purified in vitro. The BMSCs were transfected with adenovirus or adenovirus-Bcl-2. The rabbit model of MI was established by ligation of left anterior descending branch. The rabbits were injected with Ad-Bcl-2-BMSCs (MI+Bcl-2-BMSCs group), Ad-BMSCs (MI+BMSCs group) and DMEM (MI group) in infarction marginal zone 2 weeks after ligation. The cardiac function was evaluated by echocardiography.The apoptosis of myocardial cells was measured by TUNEL. The mRNA expression of VEGF was detected by real-time PCR. The expression of CD31 was examined by immunohistochemical staining, and new blood capillaries were counted at 4 weeks after BMSCs transplantation. The correlation of the above values with cardiac function was analyzed.RESULTS: The cardiac function was better, the apoptotic rate was lower, the mRNA expression of VEGF and the capillary density were higher in both MI+Bcl-2-BMSCs group and the MI+BMSCs group than those in MI group, and those in MI+Bcl-2-BMSCs group increased more obviously.The left ventricular ejection fraction (LVEF) had a negative correlation with the myocardial cell apoptosis rate. A positive correlation with the mRNA expression level of VEGF and the capillary density was also observed.CONCLUSION: The transplantation of BMSCs modified by bcl-2 gene significantly reduces the myocardial cell apoptosis, promotes angiogenesis, improves heart function of the rabbits with MI.     

Captopril down-regulates KDR/Flk-1 and its mRNA expression in the ischemic rat myocardium

AIM: We observed the expression of KDR/Flk-1 in post-myocardiac ischemia (MI) SD rats in order to explain the effect of captopril and its relationship with myocardium angiogenesis after long-term administration. METHODS: The MI model was made by LAD ligation. Captopril was administered for 6 weeks. Immuohistological method and FQ-PCR were used to test the myocardium KDR/Flk-1 expression. RESULTS: In captopril group, no inhibitory effect was observed in myocardium factor VIII expression, but KDR/Flk-1 decreased. The copies of KDR/Flk-1 mRNA reduced dramatically when compared to control group, false-operation and normal group (P<0.05, P<0.01, P>0.05). CONCLUSION: ACEI down-regulates KDR/Flk-1 and its mRNA expression in ischemic rat myocardium after long-term administration of captopril, but does not inhibit angiogenesis. So we suspect that some other pathways exist, which can not affect by ACEI, or that ACEI just reduces abnormal angiogenesis.