肾血管性高血压大鼠心脏肥厚不同时期血浆及组织心钠素、内皮素含量变化

目的了解高血压心脏病左室结构、功能变化时血浆及心肌组织中心钠素(atrial natriuretic peptide ANP)、内皮素(endothelin ET)含量变化.方法应用放免法监测二肾一夹意义型(2K1C)肾血管性高血压大鼠(RHR)血浆及心肌组织中ANP、ET含量变化,并根据超声心动图评价高血压大鼠心脏结构、功能动态变化,将高血压大鼠进行分组.结果高血压左室向心性肥厚期血浆及心肌组织(左心室)中ANP、ET含量明显升高;左室离心性肥厚期血浆ET较向心性肥厚期组更高,但心肌组织中ET含量与其无显著差别,而血浆及心肌组织中ANP含量均较向心性肥厚期组低.结论 2K1C型高血压大鼠血浆及心肌组织中ANP、ET含量均升高;血浆ET与ANP含量变化在左室肥厚中可能起着更为重要作用.     

动脉血压在肾性高血压大鼠心肌α-和β肌球蛋白重链基因表达中的作用

本实验用肾性高血压大鼠模型,探讨动脉血压在心肌肥厚和肌球蛋白重链(Myosinheavy chain,MHC)基因表达中的作用.结果表明:(1)二肾二夹(2K1C)肾性高血压大鼠,术后48～72h,血压升高.α-MHC基因表达减弱,β-MHC基因表达增强,左室重量/体重(LVW/BW)比值变化不明显;(2)二肾一夹(2K1C)肾性高血压大鼠术后第2～12w,动脉血压持续升高,LVW/BW比值明显升高,左心室α-MHC基因表达明显减弱,β-MHC基因表达明显增强;(3)血管紧张素转换酶抑制剂、巯甲丙脯酸可使2K1C肾性高血压大鼠动脉血压下降,左室肥厚发生逆转,抑制左心室α-MHC基因表达减弱和β-MHC基因表达增强.这些结果提示,在肾性高血压过程中,动脉血压升高是左心室肥厚、左室心肌MHC基因转换(switch)的重要因素,肾素-血管紧张素系统可能参与肾性高血压过程中的心肌肥厚和MHC基因转换.     

牛磺酸对肾性高血压大鼠血浆及心肌血管紧张素Ⅱ、醛固酮的影响

目的　观察牛磺酸 (Tau)对肾性高血压大鼠血浆及心肌血管紧张素 (Ang )、醛固酮 (Ald)的影响。方法　Wistar大鼠随机分为假手术组 (Sham组 )、二肾一夹肾性高血压模型组 (2 K1C组 )、Tau治疗组 (2 K1C+Tau组 ) ,每组 8只。测定并比较各组尾动脉收缩压 (SBP)、左心室重量指数 (L VWI)、心肌胶原含量、心肌纤维直径、血浆及心肌 Ang 、Ald含量。结果　 2 K1C组大鼠 SBP、L VWI、心肌胶原含量、心肌纤维直径、血浆及心肌 Ang 、Ald含量较 Sham组显著增加 (P<0 .0 1)。牛磺酸 (5 0 mg/ kg· d)治疗 8周显著降低 2 K1C大鼠 SBP、L VWI、心肌胶原含量、心肌纤维直径、血浆及心肌 Ang 和 Ald含量 (P<0 .0 1)。结论　牛磺酸可降低肾性高血压大鼠循环及心肌局部肾素血管紧张素醛固酮系统 (RAAS)活性 ,抑制心肌细胞肥大及胶原增生 ,有效防治左室肥厚     

β1受体反义寡核苷酸对肾性高血压大鼠左室重塑及心肌细胞外基质的影响

目的观察β 1受体反义寡核苷酸对肾性高血压大鼠降压和预防心室重塑的作用.方法 建立两肾一夹(2K1C)大鼠肾血管性高血压心肌肥厚模型术后4周随机分为4组(1)β 1反义寡核苷酸组;(2)反向寡核苷酸组;(3)2K1C对照组;(4)假手术组.8周后行血流动力学分析,应用病理学方法评价整体心肌肥厚和组织胶原的表达.免疫组化方法检测MMP-2、TIMP-2的表达情况.结果 与假手术组相比,两肾一夹组大鼠术后发生明显左心室肥厚和纤维化,心率(HR)、收缩压(SBP)、左室收缩压(LVSP)、左室舒张末压(LVEDP)﹑左室重量指数(LVWI)﹑胶原的含量及MMP-2、TIMP-2的表达显著高于健康的对照组,左室最大收缩和舒张速率(±dp/dtmax)均显著降低.β 1受体反义寡核苷酸能降低HR、SBP、LVSP、LVEDP、LVWI,而±dp/dtmax均显著升高;减少左室心肌中总体胶原中的合成及MMP-2、TIMP-2表达.结论 β 1受体反义寡核苷酸改善血流动力学和左室功能;有效地防止心肌肥厚及细胞外重塑,这一效应与其降低心肌中高表达的MMP-2有关.     

β1受体反义寡核苷酸对肾性高血压大鼠左室重塑及心肌细胞外基质的影响

目的　观察β1受体反义寡核苷酸对肾性高血压大鼠降压和预防心室重塑的作用。方法　建立两肾一夹(2K1C)大鼠肾血管性高血压心肌肥厚模型术后 4 周随机分为 4 组:(1)β1 反义寡核苷酸组;(2)反向寡核苷酸组;(3)2K1C对照组;(4)假手术组。8周后行血流动力学分析,应用病理学方法评价整体心肌肥厚和组织胶原的表达。免疫组化方法检测 MMP- 2、TIMP- 2 的表达情况。结果　与假手术组相比,两肾一夹组大鼠术后发生明显左心室肥厚和纤维化,心率(HR)、收缩压(SBP)、左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室重量指数(LVWI)、胶原的含量及 MMP 2、TIMP- 2的表达显著高于健康的对照组,左室最大收缩和舒张速率(±dp/dtmax)均显著降低。β1 受体反义寡核苷酸能降低HR、SBP、LVSP、LVEDP、LVWI,而±dp/dtmax均显著升高;减少左室心肌中总体胶原中的合成及MMP -2、TIMP -2表达。结论　β1受体反义寡核苷酸改善血流动力学和左室功能;有效地防止心肌肥厚及细胞外重塑,这一效应与其降低心肌中高表达的MMP 2有关。     

高盐饮食对大鼠左室肥厚的影响

目的　观察高盐饮食对原发性高血压大鼠 (SHR)及正常血压大鼠 (WKY)左室肥厚的影响 ,并探讨其可能机制。方法　SHR和WKY各 2 0只分别分为两组 :( 1)高盐饮食组SHRSL(n =10 )和WKYSL(n =10 )饮用含 2 %NaCl盐水 ;( 2 )正常盐饮食组SHRNS(n =10 )和WKYNS(n =10 )饮用不含NaCl清水 ,共饲养 6周。测量左室重量指数 (LVI) ,心肌细胞直径(CMD) ,放免测定循环ANP以及心肌局部ET 1含量。结果　 ( 1)左室重量指数及心肌细胞直径SHRSL较SHRNS显著增加(P <0 0 1) ,WKYSL较WKYNS有所增加 ,但差异不显著 (P >0 0 5 ) ;( 2循环中ANP浓度WKYSL较WKYNS明显升高 (P <0 0 1) ,SHRSL较SHRNS无明显差别 (P >0 0 5 ) ;( 3 )左室局部ET 1:SHRSL较SHRNS显著增加 (P <0 0 1) ,WKYSL较WKYNS无明显差别 (P >0 0 5 )。结论　高盐饮食可引起SHR左室肥厚 ,盐负荷后SHR心肌局部ET 1含量的增加可能是SHR左室肥厚的原因之一     

L-精氨酸对肾性高血压心肌肥厚大鼠左心室肌原癌基c-fos蛋白表达及血浆NO含量的影响

目的:探讨L-精氨酸对肾性高血压心肌肥厚大鼠左室肌原癌基因c-fos表达及血浆NO含量的影响.方法:采用免疫组织化学方法测定左室肌原癌基因c-fos蛋白表达,用比色法测定血浆一氧化氮含量.结果:通过8周治疗后,L-Arg使高血压心肌肥厚大鼠c-fos蛋白表达显著减少(P<0.005),使血浆中NO含量显著升高(P<0.001)结论:L-Arg治疗高血压心肌肥厚大鼠能减轻c-fos表达和提高血浆中NO含量.     

肾血管性高血压大鼠外周血管生成素2的变化及替米沙坦的干预作用

目的:研究血管生成素-2(angiopoietin-2,Ang-2)在肾血管性高血压及心肌肥厚进展中的作用,并探讨替米沙坦对肾血管性高血压、心肌肥厚、心脏功能及外周Ang-2水平的影响。方法:清洁级雄性SD大鼠24只,随机分为对照组、假手术组、两肾一夹(two-kidney one clip,2K1C)组和2K1C+替米沙坦组。2K1C组及2K1C+替米沙坦组采用2K1C方法制备高血压模型,其中2K1C+替米沙坦组每天以替米沙坦10mg/kg灌胃干预,2K1C组采用等量蒸馏水灌胃。分别于术前及术后经动脉插管测血压,8周时以超声心动图检测心脏结构及功能变化,随后处死大鼠,取外周动脉血清以ELISA方法检测Ang-2水平。结果:(1)与对照组、假手术组相比,2K1C组血压显著升高、心肌肥厚明显(P0.01);2K1C+替米沙坦组血压较2K1C组明显降低,心肌肥厚亦明显减轻(P0.01);(2)与对照组、假手术组相比,2K1C组动脉血清Ang-2水平明显升高(P0.01),且与血压水平、心肌肥厚程度呈正相关;2K1C+替米沙坦组Ang-2水平与2K1C组差异无统计学意义(P0.05)。结论:Ang-2在肾血管性高血压外周动脉血清中表达增加,且与心肌肥厚相关;替米沙坦可显著降低肾血管性高血压大鼠的血压、抑制心肌肥厚,对外周血清Ang-2水平无明显影响,提示替米沙坦降压机制可能与Ang-2无关。     

Toll样受体在GOldblatt鼠左室心肌中的表达-炎症与左心室肥厚相关的一个证据

目的观察肾血管性高血压大鼠(2K1C,Goldblatt高血压大鼠)左室心肌中Toll样受体4(Toll-like receptor 4,TLR4)、核因子κB(NFκB)的表达情况并探讨其影响因素.方法采用免疫组化法检测10只雄性Goldblatt高血压大鼠和6只正常雄性Sprague-Dawley(SD)大鼠左室心肌中TLR4、核因子κB的表达情况,维多利亚蓝-丽春红法行心肌胶原染色评价心肌纤维化程度,根据超声心动图评价左室结构和功能.结果高血压大鼠左室心肌组织中TLR4和NFκB的表达水平升高(P＜0.01),两者呈高度正相关(r=0.824,P＜0.01);TLR4表达水平与左室心肌纤维化呈正相关;TLR4表达水平与左室心肌肥厚程度、收缩功能指数显著相关.结论TLR4信号通路的活化可能参与Goldblatt大鼠心肌肥厚的发生和发展.     

决明子蒽醌苷对两肾一夹高血压大鼠左室心肌肥厚及舒张功能的影响

目的观察决明子蒽醌苷对两肾一夹高血压大鼠心室肌肥厚及舒张功能的影响。方法复制两肾一夹高血压大鼠动物模型,随机分为模型组、0.2、0.4 g/kg决明子蒽醌苷组及佐芬普利(0.01 g/kg)组。另取10只大鼠作为假手术组。各组大鼠灌胃给药8 w。给药后第57天测量大鼠颈动脉平均压(m CAP)、左室舒张末期压(LVEDP)、左室压力最大下降速率(LV-dp/dtmax)及左室质量与胫骨长度比值(LVW/TL)。制备心肌组织匀浆,放免法测定上清液中血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)及内皮素(ET)含量。结果决明子蒽醌苷能明显抑制两肾一夹高血压大鼠的左心室肥厚,改善心室舒张功能,与模型组比较,LVW/TL、LVEDP值明显降低、LV-dp/dtmax值明显升高(P<0.05或P<0.01),该作用与其抑制心内AngⅡ、ALD及ET表达有关(P<0.05或P<0.01)。结论明子蒽醌苷能抑制肾源性高血压所致心肌肥厚,改善心室舒张功能,且其能够有效降低心脏局部AngⅡ、ALDAET分泌有关。     

背向散射技术与彩色室壁运动技术在高血压左室重构中的应用

目的 探讨背向散射和彩色室壁运动参数评估原发性高血压不同左室构型心肌病变程度和局部室壁运动的临床价值。方法 测定70例原发性高血压病患者和31例正常对照者室间隔及左室后壁的背向散射参数和局部室壁收缩期位移。共收入正常构型组18例，向心重构组17例，向心肥厚组23例，离心肥厚组12例。结果 高血压各组室间隔超声背向散射(IB％)均不同程度地增大，以向心性肥厚组和离心性肥厚组为著；左室后壁IB％在向心性肥厚组和离心性肥厚组增高，以离心性肥厚组为著；室间隔周期变化幅度(cvlB)在向心性肥厚组和离心性肥厚组减低；左室后壁的CVIB在离心性肥厚组显著减低；高血压各组均未出现明显的背向散射跨壁梯度的改变。室间隔和左室后壁的SEM在离心性肥厚组显著减低，其余各组间虽无明显统计学差异，但在向心性肥厚组呈现增加的趋势。在离心性肥厚组，收缩期CK色带变薄或消失，色带不完整。结论 心肌超声背向散射参数可用于判断高血压不同左室构型心肌病变的程度；彩色室壁运动技术可用于评估高血压不同左室构型局部室壁运动状态。     

Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension.

The spectrum of left ventricular geometric adaptation to hypertension was investigated in 165 patients with untreated essential hypertension and 125 age- and gender-matched normal adults studied by two-dimensional and M-mode echocardiography. Among hypertensive patients, left ventricular mass index and relative wall thickness were normal in 52%, whereas 13% had increased relative wall thickness with normal ventricular mass ("concentric remodeling"), 27% had increased mass with normal relative wall thickness (eccentric hypertrophy) and only 8% had "typical" hypertensive concentric hypertrophy (increase in both variables). Systemic hemodynamics paralleled ventricular geometry, with the highest peripheral resistance in the groups with concentric remodeling and hypertrophy, whereas cardiac index was super-normal in those with eccentric hypertrophy and low normal in patients with concentric remodeling. The left ventricular short-axis/long-axis ratio was positively related to stroke volume (r = 0.45, p less than 0.001), with cavity shape most elliptic in patients with concentric remodeling and most spheric in those with eccentric hypertrophy. Normality of left ventricular mass in concentric remodeling appeared to reflect offsetting by volume "underload" of the effects of pressure overload, whereas eccentric hypertrophy was associated with concomitant pressure and volume overload. Thus, arterial hypertension is associated with a spectrum of cardiac geometric adaptation matched to systemic hemodynamics and ventricular load. Concentric left ventricular remodeling and eccentric hypertrophy are more common than the typical pattern of concentric hypertrophy in untreated hypertensive patients.     

易卒中型肾血管性高血压大鼠的心脏损害

通过观察易卒中型肾血管性高血压大鼠心脏的病理形态．发现所有高血压大鼠均有不同程度的左心室肥厚和心肌内小冠状动脉病变，但大冠状动脉无粥样硬化，在此基础上自发性心肌梗塞率为41．8％。表明心室肥厚和心肌内小冠状动脉病变在高血压所致的心肌缺血性损害中起重要作用。     

Effect of Long-Term Treatment with Diltiazem on Atrial Natriuretic Peptides in Spontaneously Hypertensive Rats

ABSTRACT

The present study was designed to examine the possible effect of long-term treatment with diltiazem on plasma and atrial concentrations of atrial natriuretic peptides (ANP) in spontaneously hypertensive rats (SHR). Diltiazem treatment reduced blood pressure and ventricular weight in SHR. Plasma ANP concentration in untreated SHR was higher than Wistar-Kyoto rats (WKY). Diltiazem treatment decreased plasma ANP concentration in SHR near to the level of WKY; moreover, plasma ANP concentration was correlated with blood pressure and ventricular weight in treated and untreated SHR. Left atrial ANP concentration in untreated SHR was lower than WKY. Diltiazem treatment increased left atrial ANP concentration in SHR, but this effect was not noted in WKY. These results suggest that the ANP release from the left atrium is chronically stimulated in adult SHR, and that the prevention of an increase in plasma ANP by diltiazem treatment may be, in part, attributed to the improvement of cardiac overload induced by reductions in blood pressure and cardiac hypertrophy.     

内皮素在大鼠高血压心肌肥大中的作用

目的研究内皮素（ＥＴ）在一氧化氮合酶（ＮＯＳ）抑制剂亚硝基左旋精氨酸甲酯（Ｌ－ＮＡＭＥ）诱导的高血压心肌肥大中的作用及ＥＴＡ受体阻断剂ＪＫＣ－３０１的保护效应。方法复制大鼠Ｌ－ＮＡＭＥ高血压模型，动物分对照组、高血压组和ＪＫＣ－３０１治疗组，测定心重、血浆及心肌ＥＴ水平和心肌丝裂素活化蛋白激酶（ＭＡＰＫ）活性。结果高血压动物的心重、ＥＴ水平和心肌ＭＡＰＫ活性较对照组都显著升高（Ｐ＜０．０１或０．０５），加用ＪＫＣ－３０１治疗则较高血压组ＥＴ水平不变，但血压、心重和ＭＡＰＫ活性均降低（Ｐ＜０．０１或０．０５），心肌ＭＡＰＫ活性与左心室肥大程度呈正相关（ｒ＝０．８２，Ｐ＜０．０１）。结论一氧化氮缺乏的心肌肥大可能是由ＥＴ所介导的，ＥＴＡ受体阻断剂对此种肥大有防治作用     

Role of nisoldipine on blood pressure, cardiac hypertrophy, and atrial natriuretic peptides in spontaneously hypertensive rats

The effect of long-term treatment with the calcium antagonist nisoldipine on development of hypertension, cardiac hypertrophy, and plasma levels of atrial natriuretic peptides (ANP) was determined in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) of the same age. Measurement of immunoreactive ANP in plasma provided a sensitive marker for the severity of hypertension and the associated cardiac overload. Long-term treatment with nisoldipine prevented the development of hypertension, the associated heart failure, and the increase of plasma levels of ANP in SHR but had no effect on systolic blood pressure, heart weight, and plasma levels of ANP in WKY. In addition, nisoldipine had a therapeutic effect in old SHR with manifest cardiac failure in end-stage hypertension, as evidenced not only by the reduction of blood pressure but also by the reduction of cardiac hypertrophy, of elevated immunoreactive ANP in plasma, and of increased plasma renin activity.     

Hemodynamic hypertrophied left ventricular patterns in systemic hypertension

The hemodynamic pattern of hypertrophied left ventricle in systemic hypertension was studied by M-mode echocardiography in 42 untreated hypertensive patients with left ventricular (LV) mass index greater than 2 standard deviations from the sex-specific mean of 114 normal subjects (normal values of our laboratory), and in 45 normotensive volunteers. Hypertensive patients showed cardiac dimensions, relative diastolic wall thickness, ratio of systolic pressure to end-systolic dimension, cardiac index and stroke index greater than normotensive control subjects (0.01 less than p less than 0.0001). Pressure/dimension ratio was correlated to relative wall thickness (p less than 0.005). End-systolic stress/volume ratio was normal as was systolic pressure to dimension ratio normalized for end-diastolic wall thickness. LV hypertrophy was concentric in 26% and eccentric in 74% of patients and suggested 2 different heart adaptations to overload: eccentric hypertrophy was associated with increased cardiac dimensions, high peak stress, normal systolic function and moderately increased LV contractility; concentric hypertrophy was associated with the highest blood pressure values, normal cardiac dimension, normal peak stress, normal systolic function and much increased LV contractility. Because stress/volume ratio and wall thickness-corrected systolic pressure/dimension ratio were normal in hypertensive patients, LV contractile capacity might be supported by the increase in myocardium available for contraction, rather than by increase in inotropic state.     

Effect on atrial natriuretic peptides of chronic treatment with alpha-methyldopa and hydralazine in spontaneously hypertensive rats

The present study was designed to examine the effect of antihypertensive therapy on plasma and atrial concentration of atrial natriuretic peptides (ANP) in spontaneously hypertensive rats (SHR) by using alpha-methyldopa and hydralazine. Methyldopa and hydralazine treatment reduced blood pressure (P less than .05, P less than .05, respectively); however, ventricular weight was reduced by methyldopa (P less than .05) but not by hydralazine. Plasma ANP concentration in untreated SHR was higher than that observed in Wistar-Kyoto rats (WKY). Methyldopa treatment decreased plasma ANP concentration, but hydralazine treatment did not. Moreover, plasma ANP concentration and ventricular weight were positively correlated in untreated and treated SHR. The left atrial ANP concentration in untreated SHR was lower than that observed in WKY. Methyldopa treatment increased left atrial ANP concentration, but hydralazine treatment did not. These results suggest that the ANP release from the left atrium is chronically stimulated in adult SHR, and that a decrease in plasma ANP concentration by methyldopa treatment is, in part, associated with the decline of ANP release from the heart due to the reductions of blood pressure and cardiac hypertrophy.     

Relation of plasma brain and atrial natriuretic peptides to left ventricular geometric patterns in essential hypertension

We investigated whether plasma brain and atrial natriuretic peptide (BNP and ANP, respectively) levels could reflect left ventricular (LV) geometry and function in patients with mild to moderate essential hypertension. A positive correlation was found between LV mass index (LVMI) and plasma ANP levels in 84 untreated, hypertensive patients, but not between LVMI and plasma BNP levels. As compared with other geometric patterns, plasma BNP levels were increased in concentric hypertrophy, in which LVMI was increased and LV diastolic function was decreased. These data suggest that production of BNP was increased in hypertensive patients with concentric hypertrophy via LV overload or depression of diastolic function.     

Diastolic characteristics and cardiac energetics of isolated hearts exposed to volume and pressure overload

The relation between diastolic dimensions and systolic function was studied in isolated rat hearts exposed to pressure (primary hypertension) and to volume load (hyperthyroidism). The hearts were arrested in diastole and cardiac dimensions analysed. Cardiac function was determined using an anterograde working heart preparation. Both models of cardiac overload produced significant left ventricular hypertrophy, however with different design. One concentric and one eccentric form of left ventricular hypertrophy were found in the spontaneously hypertensive rat obtained from two different breeders. An even more pronounced form of eccentric left ventricular hypertrophy was seen in hyperthyroid rats. The hearts with an eccentric form of hypertrophy had a higher maximal stroke volume when perfused at a high aortic pressure than those with a concentric form. At a low aortic pressure and hence a limited coronary perfusion cardiac performance was diminished in both types of spontaneously hypertensive rats but remained normal in hyperthyroid rats. Furthermore, oxygen consumption was reduced in all hypertrophied hearts compared with non-hypertrophied hearts. These data therefore suggest (a) that hearts having an eccentric type of hypertrophy may be in a more favourable situation, delivering a higher stroke volume for a given degree of myocardial fibre shortening; and (b) that the development of coronary vascular structural changes in spontaneously hypertensive rats, thereby increasing vascular resistance, leads to a decrease in left ventricular function at a low coronary perfusion pressure, whereas no such reduction was observed in hyperthyroid hearts, probably owing to a normal vascular resistance.