Inhibition of Jak2 phosphorylation attenuates pressure overload cardiac hypertrophy

RATIONALE: We examined the role of Jak2 kinase phosphorylation in the development of pressure overload hypertrophy in mice subjected to transverse aortic constriction (TAC) and treated with tyrphostin AG490, a pharmacological inhibitor of Jak2. METHODS: Control mice (sham), subjected to TAC for 15 days (TAC) or to TAC and treated with 48 microg/kg/day i.p. of tyrphostin AG490 (TAC+AG490) were evaluated for morphological, physiological, and molecular changes associated with pressure overload hypertrophy. RESULTS: Mice subjected to TAC alone developed concentric hypertrophy that accompanied activation of the components of the Jak/STAT signaling pathway manifested by an increase in phosphorylation of Jak2 and STAT3. We also observed increased phosphorylation of MAPK p44/p42, p38 MAPK and JNK in the TAC group, as well as, an increase in expression of MKP-1 phosphatase which negatively regulates MAPK kinases. Treatment of aortic constricted mice with tyrphostin AG490 failed to develop hypertrophy and showed a marked reduction in phosphorylation of Jak2 and STAT3. There was, however, in TAC and AG490 treated mice, a notable increase in the phosphorylation state of the MAPK p44/42, whereas MKP-1 phosphatase was downregulated. CONCLUSION: These findings suggest that Jak2 kinase plays an important role in left ventricular remodeling during pressure overload hypertrophy. Pharmacological inhibition of Jak2 kinase during pressure overload blocks the development of concentric hypertrophy.     

Effects of enalapril in rats with pressure overload cardiac hypertrophy

• 1.1. The effects of the ACE inhibitor enalapril were studied in rats with cardiac hypertrophy induced by abdominal aortic constriction. This experimental model has shown that pump failure can be evidenced only during increased workload.
• 2.2. Under basal conditions, enalapril at 1–3 mg/kg induced a significant reduction in blood pressure. During the acute volume loading or the increase in afterload due to a total aortic occlusion, only rats treated with 3 mg/kg enalapril, but not 1 mg/kg, received a hemodynamic benefit that was paralleled by a significant reduction in cardiac hypertrophy.
• 3.3. The present study demonstrates that reduction in blood pressure on its own was not sufficient to improve cardiac function. A decrease in blood pressure accompanied with hypertrophy regression were necessary to normalize hemodynamic parameters in pressure-overloaded rats.

     

Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation

Aim:

To identify the role of metformin in cardiac hypertrophy and investigate the possible mechanism underlying this effect.

Methods:

Wild type and AMPKα2 knockout (AMPKα2^−/−) littermates were subjected to left ventricular pressure overload caused by transverse aortic constriction. After administration of metformin (200 mg·kg⁻¹·d⁻¹) for 6 weeks, the degree of cardiac hypertrophy was evaluated using echocardiography and anatomic and histological methods. The antihypertrophic mechanism of metformin was analyzed using Western blotting.

Results:

Metformin significantly attenuated cardiac hypertrophy induced by pressure overload in wild type mice, but the antihypertrophic actions of metformin were ablated in AMPKα2^−/− mice. Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPKα2^−/− mice.

Conclusion:

Long-term administration of metformin may attenuate cardiac hypertrophy induced by pressure overload in nondiabetic mice, and this attenuation is highly dependent on AMPK activation. These findings may provide a potential therapy for patients at risk of developing pathological cardiac hypertrophy.     

葛根素预防压力过载性心脏肥大的保护作用及机制

目的研究葛根素对心脏肥大大鼠的保护作用,并探讨其相关机制。方法将主动脉缩窄术(降主动脉结扎,aortic banding,AB)所致心脏肥大的40只雄性Spraguee Dawley大鼠(体质量80~100g),分为阳性对照组(control组)、假手术组(shamoperated,SO组)、葛根素组(Pue组)和雷帕霉素组(RAPa组)。检测各组经相应药物治疗后,腺苷酸活化蛋白激酶(5′-adenosine monophosphate kinase,AMPK)的活性及自噬功能。同时,体外检测异丙肾上腺素和3-甲基腺嘌呤所致的心肌影响。结果葛根素组治疗3周后,大鼠明显恢复自噬;葛根素治疗6周后,有效地限制大鼠心脏细胞肥大和细胞凋亡。雷帕霉素组具有相似作用。体外研究,葛根素对异丙肾上腺素所致的H9c2细胞也具有类似的抗肥大和抗细胞凋亡作用。用3-甲基腺嘌呤预处理H9c2细胞,抑制自噬功能后,葛根素的保护作用被阻断。结论葛根素通过AMPK/mTOR信号途径,部分恢复细胞自噬功能,发挥抗心脏细胞肥大和抗细胞凋亡作用。     

阿米洛利对压力超负荷心肌肥厚大鼠心肌细胞膜G蛋白的影响

目的观察阿米洛利对心肌细胞膜上Gi及GS的α亚基含量的影响。方法采用部分狭窄大鼠腹主动脉的方法建立压力超负荷心肌肥厚的模型,运用Westernblot技术。结果左室肥厚大鼠心肌细胞膜Giα与GSα含量均下降,Ami组的Giα含量较LVH组与假手术对照组之间均未见显著性差异;而GSα含量较LVH组相比有所升高,但与假手术对照组间仍有差别。结论心肌肥厚与G蛋白异常有关;阿米洛利抑制心肌肥厚的作用与GS蛋白表达相关。     

超负荷心肌肥厚心肌细胞的凋亡和增殖

在超负荷心肌肥厚过程中存在心肌细胞的凋亡和增殖,心肌细胞的凋亡可能是代偿性肥厚向心衰转变的决定因素,凋亡的发生机制涉及外在因素和一些内源性细胞通路。另一方面,心肌肥厚中既有心肌细胞的肥大,亦存在心肌细胞的增殖,心肌细胞的增殖与细胞周期素(Cyclin)、细胞周期依赖激酶(Cdk)、Cdk抑制因子(CdkI)、bcl2、p53及端粒等因子有关,心肌细胞的凋亡和增殖通过一些因子相关联。     

Salutary effects of Corydalis yanhusuo extract on cardiac hypertrophy due to pressure overload in rats

We have evaluated the effects of an alcohol extract from the rhizome of Corydalis yanhusuo W. T. (CY), a well-known traditional Chinese medicinal herb, on pressure-overloaded cardiac hypertrophy induced by transverse abdominal aorta constriction (TAAC) in rats. Rats were given vehicle or CY extract (200 or 50 mg kg(-1) per day) from the second week after induction of pressure overload, for a period of 7 weeks. Haemodynamic parameters, relative heart weight and myocyte cross-sectional area were measured in each group. We also estimated left ventricular (LV) collagen volume fraction (CVF) using Masson trichrome staining, and type I collagen expression by Western blot assay. Chronic TAAC caused notable cardiac hypertrophy and heart dysfunction. Significant collagen deposition and greater type I collagen expression were found in model control rats. These changes were not significantly reversed after treatment with 50 mg kg(-1) CY, whereas 200 mgkg(-1) significantly improved heart function and prevented cardiac hypertrophy, with parallel reductions in myocardial fibrosis, as evidenced by reduced LV CVF and reduced levels of type I collagen. In conclusion, chronic treatment of rats with CY extract attenuated development of cardiac hypertrophy.     

Hydroxysafflor yellow A attenuates left ventricular remodeling after pressure overload-induced cardiac hypertrophy in rats

Context: Hydroxysafflor yellow A (HSYA), the main chemical component of the safflower yellow pigments, is used extensively in traditional Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases.

Objective: The present study determined the effects of HSYA on left ventricular hypertrophy after pressure overload and investigated the underlying mechanisms.

Materials and methods: Cardiac hypertrophy was induced by the ligation of abdominal aorta in male Wistar rats. The rats were then divided into five groups and treated with captopril (100?mg/kg) or HSYA at different doses (0, 10, 20 and 40?mg/kg). Six weeks after treatment, the weight of left ventricle, LVMI (left ventricular mass index) and pathological changes were measured. MMP-2 (metalloproteinase 2) and MMP-9 (metalloproteinase 9) levels were determined by ELISA. Protein expressions of Bcl-2 and Bax were evaluated by immunohistochemistry.

Results: HSYA (20, 40?mg/kg) significantly attenuated the increase of LVMI (ventricular weight/body weight) by 13.04 and 30.43% respectively, when compared with the model group. This was associated with the amelioration of pathological lesion, such as cardiac muscle fibers were smaller and the nuclei of cardiomyocytes were lightly stained in animals treated with HSYA (20, 40?mg/kg). In addition, the administration of HSYA at doses of 20 and 40?mg/kg increased the Bcl-2/Bax ratio (1.17?±?0.08 and 1.39?±?0.07 versus 0.71?±?0.06). In addition, the serum MMP-2 and MMP-9 levels were blocked by the treatment at doses of 20 and 40?mg/kg HSYA (MMP-2, 76.1?±?9.2 and 65.6?±?6.8 versus 82.9?±?6.2, ng/ml; MMP-9, 66.6?±?4.8 and 57.5?±?5.0 versus 83.5?±?6.0, ng/ml).

Conclusion: These findings indicated that HSYA has beneficial effects on hypertensive ventricular remodeling, which may involve mechanisms of inhibiting cell apoptosis and suppressing metalloproteinases expression.     

瑞舒伐他汀对心肌肥厚大鼠TLR4信号通路的影响

目的研究瑞舒伐他汀(rosuvastatin,RSV)对压力负荷诱导心肌肥厚大鼠心肌中toll样受体4(TLR4)及其下游核转录因子NF-κB p65、IκBα、炎症因子TNF-α表达的影响。方法采用腹主动脉缩窄大鼠模型,♂Wistar大鼠随机分为假手术组(S)、模型组(M)、RSV给药组(R,10 mg·kg~(-1)·d~(-1))每组10只。行心脏超声学检查,采用RT-PCR、Western blot、免疫组化、ELISA等方法检测心肌组织中心肌肥大基因ANP及TLR4、NF-κB p65、IκBα、TNF-α的表达。将TLR4蛋白水平分别与ANP、NF-κB p65、TNF-α水平进行相关性分析。结果 M组与S组相比,心脏体积和心肌细胞横截面直径、ANP mRNA水平均明显增加(P<0.01),伴TLR4mRNA和蛋白、NF-κB p65及TNF-α的水平明显增加及IκBα蛋白水平减少(P<0.05)。RSV抑制心肌肥厚,下调心肌组织中TLR4mRNA和蛋白、NF-κB p65及TNF-α的表达及上调IκBα蛋白水平(P<0.05)。在M组和R组,TLR4蛋白水平分别与ANP、NF-κB p65、TNF-α水平呈正相关。结论 RSV抑制心脏压力负荷诱导的心肌肥厚的作用可能与其抑制TLR4信号系统有关。     

Knockout of beta(1)- and beta(2)-adrenoceptors attenuates pressure overload-induced cardiac hypertrophy and fibrosis

BACKGROUND AND PURPOSE: The role of beta-adrenoceptors in heart disease remains controversial. Although beta-blockers ameliorate the progression of heart disease, the mechanism remains undefined. We investigated the effect of beta-adrenoceptors on cardiac hypertrophic growth using beta(1)- and beta(2)-adrenoreceptor knockout and wild-type (WT) mice.EXPERIMENTAL APPROACH :Mice were subjected to aortic banding or sham surgery, and their cardiac function was determined by echocardiography and micromanometry.KEY RESULTS: At 4 and 12 weeks after aortic banding, the left ventricle:body mass ratio was increased by 80-87% in wild-type mice, but only by 15% in knockouts, relative to sham-operated groups. Despite the blunted hypertrophic growth, ventricular function in knockouts was maintained. WT mice responded to pressure overload with up-regulation of gene expression of inflammatory cytokines and fibrogenic growth factors, and with severe cardiac fibrosis. All these effects were absent in the knockout animals.CONCLUSION AND IMPLICATIONS:Our findings of a markedly attenuated cardiac hypertrophy and fibrosis following pressure overload in this knockout model emphasize that beta-adrenoceptor signalling plays a central role in cardiac hypertrophy and maladaptation following pressure overload.     

An antidiabetic thiazolidinedione induces eccentric cardiac hypertrophy by cardiac volume overload in rats

1. To assess the involvement of volume overload in the development of cardiac hypertrophy during treatment with an antidiabetic thiazolidinedione, changes in cardiac anatomy and parameters of cardiac volume overload were evaluated in female Sprague-Dawley rats treated with the thiazolidinedione derivative T-174. 2. Two week administration of T-174 (13 and 114 mg/kg per day) increased absolute and relative heart weights by 11-24%, demonstrating the development of cardiac hypertrophy. There was no evidence of oedema in hearts from treated rats. 3. Both plasma and blood volumes were increased in T-174-treated rats without any changes in systolic blood pressure and heart rate, whereas haematocrit was decreased. In accordance with the existence of volume overload, both left ventricular end-diastolic pressure and right atrial pressure were increased. Morphometric analysis of hearts revealed that T-174 induced eccentric heart hypertrophy, as characterized by a small increase in wall thickness and a large increase in the chamber volume, which is characteristic of volume overload. Volume overload is suggested as the possible trigger mechanism because blood volume expansion preceded cardiac hypertrophy and there was a high correlation between heart weight and blood volume. 4. T-174-treated streptozotocin-induced diabetic rats also exhibited blood volume expansion and cardiac hypertrophy. 5. These findings suggest that cardiac volume overload is induced by plasma volume expansion and contributes to the development of eccentric cardiac hypertrophy during treatment with antidiabetic thiazolidinediones. Although thiazolidinediones are insulin-sensitizing agents, these cardiac effects are likely to be mediated independently of insulin.     

吡格列酮体外对大鼠心肌肥大的改善作用

目的　探讨噻唑烷二酮 (TZD)类药物吡格列酮在体外对心肌肥大的影响。方法　新生大鼠的原代培养心肌细胞和非心肌细胞 ,以血管紧张素Ⅱ (AngⅡ )刺激建立体外心肌肥大模型 ,并用不同浓度的吡格列酮作用细胞。采用RT PCR法检测心肌肥大特征性基因心钠肽 (ANP)和脑钠肽(BNP)的mRNA表达 ,以MTT比色法和3 H TdR参入实验检测非心肌细胞增殖情况 ,以3 H 亮氨酸参入实验检测心肌细胞蛋白合成速率 ,并用软件分析心肌细胞表面积。结果　肥大模型出现后 ,心肌细胞表面积、ANP和BNP的mRNA表达以及蛋白合成速率增加 ;非心肌细胞增殖活跃 ,但ANP和BNP的mRNA表达没有变化。吡格列酮可以逆转这些变化 ,同时下调非心肌细胞的ANP和BNP的mRNA表达 ,并呈一定的剂量依赖性。结论　吡格列酮体外对大鼠心肌肥大有改善作用 ,预示着TZD类药物具有防治心肌肥大等心血管疾病的药理作用     

Effects of indapamide in rats with pressure overload left ventricular hypertrophy

We studied the in vivo effects of the antihypertensive diuretic agent indapamide on left ventricular (LV) morphology in chronically pressure-overloaded rat hearts. LV pressure and subsequently LV mass were increased by banding the ascending aorta over a period of 6 weeks. Thereafter, animals were treated with low-dose (1 mg/kg/day, n = 9) or high-dose (10 mg/kg/day, n = 9) indapamide for another 6 weeks. Low-dose indapamide treatment reduced LV weights as compared with vehicle-treated controls (n = 9; -12%; p = 0.008). Furthermore, low-dose indapamide treatment resulted in a decrease of myocyte volume (59.0 +/- 10.6 vs. 79.0 +/- 9.8 m3 x 10(-27); p < 0.05) and an improvement of molecular markers of hypertrophy: a reduction of LV atrial natriuretic factor mRNA expression (-37%; p < 0.05), and an increase of the V1/V3 myosin ratio (+121%; p < 0.05). Low-dose indapamide also reduced significantly plasma (-65%) and LV angiotensin-converting enzyme (ACE) activities (-74%) as well as LV mRNA levels (-24%). These changes were observed despite continued pressure overload of the LV and despite a lack of significant changes in sodium excretion with the prolonged administration of low-dose indapamide. High-dose indapamide treatment showed no significant effects on LV mass, structure, and gene expression. Furthermore, high-dose indapamide increased plasma renin activity substantially, whereas low-dose treatment was without effect on circulating renin. In conclusion, in rats with continuous LV pressure-overload low-dose treatment with indapamide leads to mild regression of cardiac hypertrophy, accompanied by a downregulation of components of the cardiac renin-angiotensin system. These effects may be mediated by mechanisms apart from the known diuretic and antihypertensive actions of indapamide, because sodium excretion and blood pressure were stable with long-term treatment and are unlikely to be related to LVH regression in this model.     

Interaction between renin–angiotensin and sympathetic nervous systems in a rat model of pressure overload cardiac hypertrophy

1 A raised cardiac workload activates neurohormones which will increase muscle mass and shift contractility to the right along the Frank‐Starling curve. 2 This study examined the interaction between the SNS and RAS in contributing to vascular responsiveness following the development of cardiac hypertrophy due to aortic banding. 3 Sprague Dawley rats (180–200 g) were assigned to one of six groups; Normal, Sham‐operated, Aortic Banded (AB), Aortic Banded treated with losartan (ABLOS), Aortic Banded treated with 6‐hydroxydopamine (ABSYMP) and Aortic banded treated with both losartan and 6‐hydroxydopamine (ABSYMPLOS). A constricting band was placed around the supra renal aorta on day zero with drug treatment from day 37 to day 44. Vasopressor responses to noradrenaline, phenylephrine, methoxamine and angiotensin II were measured on day 45. 4 The magnitudes of the MAP responses to all vasoactive agents, expressed as percentage changes, were similar in Normal and Sham groups, but reduced in the AB group. ABLOS group showed attenuated response to ANGII whereas all responses were enhanced in the ABSYM group. 5 A positive interaction between the two systems was observed with α_1A‐adrenoceptors identified as a major component of SNS and AT₁ receptors of RAS to induce vasopressor effects.     

卡托普利对实验大鼠左室肥厚的干预作用

目的观察卡托普利逆转压力负荷增加大鼠左室肥厚的作用。方法采用腹主动脉狭窄所致压力负荷增加大鼠左室肥厚模型,将雄性SD大鼠36只随机分为假手术组、模型组、卡托普利组,观察用药4周后左室重量指数（LVMI）、左室心肌病理形态HE染色、左室心肌细胞超微结构等指标的改变。结果模型组LVMI明显高于假手术组（P〈0．01）,卡托普利组（2．32±0．35）明显低于模型组（2．98±0．36）,P〈0．01;左室心肌病理形态HE染色、左室心肌细胞超微结构的改变与LVMI的改变基本一致。结论卡托普利具有逆转心肌肥厚的作用。     

Qiliqiangxin inhibits the development of cardiac hypertrophy, remodeling, and dysfunction during 4 weeks of pressure overload in mice

Qiliqiangxin (QL), a traditional Chinese medicine, has been used in the treatment of chronic heart failure. However, whether QL can benefit cardiac remodeling in the hypertensive state is unknown. We here examined the effects of QL on the development of cardiac hypertrophy through comparing those of losartan in C57BL/6 mice underlying transverse aorta constriction for 4 weeks. QL and losartan were administrated at 0.6 mg and 13.4 mg·kg·d, respectively. Cardiac hypertrophy, function, and remodeling were evaluated by echocardiography, catheterization, histology, and examination of specific gene expression and ERK phosphorylation. Cardiac apoptosis, autophagy, tumor necrosis factor α/insulin-like growth factor-1, and angiotensin II type 1 receptor expression and especially the proliferation of cardiomyocytes and phosphorylation of ErbB receptors were examined in vivo to elucidate the mechanisms. Transverse aorta constriction for 2 weeks resulted in a significant cardiac hypertrophy, which was significantly suppressed by either QL or losartan treatment. At 4 weeks after transverse aorta constriction, although the development of cardiac dysfunction and remodeling and the increases in apoptosis, autophagy, tumor necrosis factor α/insulin-like growth factor-1, and angiotensin II type 1 receptor expression were abrogated comparably between QL and losartan treatments, QL, but not losartan, enhanced proliferation of cardiomyocytes, which was paralleled with dowregulation of CCAAT/enhancer-binding protein β, upregulation of CBP/p300-interacting transactivator with ED-rich carboxy-terminal domain 4, and increases in ErbB2 and ErbB4 phosphorylation. Furthermore, inhibition of either ErbB2 or CBP/p300-interacting transactivator with ED-rich carboxy-terminal domain 4 abolished the cardiac protective effects of QL. Thus, QL inhibits myocardial inflammation and cardiomyocyte death and promotes cardiomyocyte proliferation, leading to an ameliorated cardiac remodeling and function in a mouse model of pressure overload. The possible mechanisms may involve inhibition of angiotensin II type 1 receptor and activation of ErbB receptors.     

赖诺普利与氯沙坦预防压力负荷性心肌肥厚的实验研究

目的 探讨大鼠心肌肥厚时心血管重构的结构、生化改变及赖诺普利与氯沙坦对心血管重构的预防作用。方法 膈下腹主动脉缩窄法建立大鼠心肌肥厚模型。假手术组、模型组、降压和非降压剂量赖诺普利与氯沙坦在术后第2天用药至30天后，检测平均动脉压(MAP)、心肌肥厚程度及局部心肌组织一氧化氮(N0)、一氧化氮合酶(NOS)和胶原蛋白含量。结果 (1)与假手术组相比，模型组MAP、左室重量(LVW)、左室重量指数(LVMI)、心肌细胞横径(TDM)、胶原蛋白分别提高28．6％、20．5％、26．9％、17．9％、54．4％(P＜0．01)；NO、NOS分别降低53．4％、51．2％(P＜0．01)。(2)降压剂量赖诺普利与氯沙坦和非降压剂量氯沙坦干预后，LVW、LVMI、TDM、NO、NOS、胶原蛋白含量与假手术组无明显差异。非降压剂量赖诺普利可使LVW、LVMI和TDM下降，但仍高于假手术组(P＜0．01)，NO、NOS改善不明显；(3)LVMI与MAP、胶原蛋白含量均呈正相关(分别为γ=0．7841，γ=0．8177，P＜0．01)，与NO显负相关(γ=-0．7730，P＜0．01)。结论 心血管重构与血压、心脏间质成分及NO有密切关系；赖诺普利预防心肌肥厚可能是血流动力学和非血流动力学因素共同作用的结果；氯沙坦可能主要依靠非血流动力学因素抗心肌肥厚。     

西红花酸对压力超负荷所致大鼠心肌肥厚的影响

目的研究西红花酸对压力超负荷所致大鼠心肌肥厚的影响。方法腹主动脉部分狭窄术致心肌肥厚,采用试剂盒测定Na⁺-K⁺ ATPase和Ca²⁺-Mg²⁺ ATPase的活力及羟脯氨酸的含量,SDS-PAGE检测MMPs的活力。结果 模型组ATPase活性降低更加明显,羟脯氨酸的含量明显增加,MMPs活力明显增强。西红花酸能显著提高心肌组织的ATPase活力,降低胶原的含量,抑制MMPs的活力。结论西红花酸对压力超负荷所致大鼠心肌肥厚具有一定的改善作用,抑制MMPs的活性可能是其作用机制之一。     

氯沙坦和雷米普利对压力过载引起的左心室肥厚作用的比较观察

目的：应用氯沙坦和雷米普利来探讨血管紧张肽Ⅱ对压力过载引起的左心室肥厚的相关作用。方法：采用缩窄大鼠肾动脉间腹主动脉的方法造成后负荷过载所致的左心室肥厚模型。造模后12 wk,分别给予灌服氯沙坦(1.0 mg·kg~(-1))和雷米普利(1.0 mg·kg~(-1))。给药12 wk后,应用形态测量学测定左室重量指数；Langendorff离体心脏灌流法测定离体心功能和右颈总动脉插管法测定在体心功能及血流动力学；应用酶联免疫吸附法测定大鼠血浆血管紧张肽Ⅱ(AngⅡ)、醛甾(固)酮(Ald)含量和心肌组织AngⅡ含量。结果：与模型动物比较,氯沙坦和雷米普利均能降低左室重量指数；在体大鼠血流动力学的测定中发现,压力过载造成大鼠动脉血压和左室收缩压显著升高,应用氯沙坦和雷米普利治疗后,明显改善大鼠心脏收缩功能,降低左室收缩压和外周动脉血压；离体大鼠心功能测定发现,压力过载引起离体大鼠心脏左室舒张压和左室最大上升速率下降,氯沙坦和雷米普利不能改善左室舒张压和左室最大上升速率下降。此外,氯沙坦和雷米普利能够降低心室重构过程中血浆和心肌组织中AngⅡ的含量以及血浆中Ald含量。结论：应用氯沙坦和雷米普利均能够降低缩窄大鼠腹主动脉造成的左心室肥厚,进一步提示AngⅡ在慢性压力过载导致左心室重构中起着关键性作用。