三七总皂苷对异丙肾上腺素所致大鼠心肌肥厚和纤维化的影响

目的：研究三七总皂苷（PNS）对异丙肾上腺素所致大鼠心肌肥厚和纤维化的保护作用。方法： 用异丙肾上腺素（ISO）5 mg·kg^-1·d^-1,sc,连续7 d，建立大鼠心肌肥厚和纤维化模型。造模第2 d开始给大鼠腹腔注射PNS 25和50 mg· kg^-1·d^-1,连续14 d，测定全心重量指数（HW/BW）、左心室重量指数（LVW/BW即LVI）；采用试剂盒用分光光度法检测左心室心肌组织中羟脯氨酸（Hyp）、丙二醛（MDA）、一氧化氮（NO）含量和超氧化物歧化酶（SOD）、谷光苷肽过氧化酶（GSH-Px）、一氧化氮合酶（NOS）活性；用放免分析法检测左心室心肌组织中血管紧张素Ⅱ（AngⅡ）含量。结果： ISO模型组大鼠的HW/BW、LVI、左心室HyP、AngⅡ、MDA含量和诱生型NOS(iNOS)活性显著高于生理盐水对照组，SOD、GSH-Px及结构型NOS(cNOS)活性和NO含量明显比生理盐水对照组低；PNS治疗组左心室心肌组织中NO含量、cNOS 、SOD和GSH-Px活性明显高于ISO模型组；MDA和AngⅡ含量及iNOS活性和心脏重量指数比ISO模型组低。结论： PNS有抗心肌肥厚和纤维化作用，该作用与清除氧自由基及升高NO含量有关。     

卡托普利对实验性腹主动脉狭窄大鼠左心室肥厚的影响

目的进一步证实实验性腹主动脉狭窄大鼠左心室肥厚及卡托普利的作用。方法采用实验性腹主动脉银夹狭窄大鼠模型,观察左心室重量指数（ＬＶＭＩ）,放免测定血浆血管紧张素Ⅱ（ＡｎｇⅢ）及左心室心肌局部 Ａｎｇ Ⅱ。结果模型组ＬＶＭＩ、血浆ＡｎｇⅡ、左心室心肌Ａｎｇ　Ⅱ水平明显高于假手术组;卡托普利组ＬＶＭＩ、血浆Ａｎｇ Ⅱ、左心室心肌Ａｎｇ　Ⅱ明显下降。结论使用腹主动脉银夹狭窄方法建立心脏后负荷增加的心肌肥厚动物模型是可靠的,卡托普利确有抗心肌肥厚的作用。     

ILK在异丙肾上腺素诱导大鼠心肌肥厚组织中的表达

目的探讨心肌肥厚发生发展过程中ILK的表达特征。方法在大鼠背部皮下分别注射7、28和56 d异丙肾上腺素(ISO),判定心肌肥厚指标,利用免疫组织化学和免疫印迹技术,观察ILK在肥厚左心室肌中的表达。结果 ILK主要表达于心肌细胞胞膜和内皮细胞。与对照组相比,ISO组ILK阳性表达明显增强。随着造模时间的延长,肥厚心肌中ILK的表达含量逐渐升高。Western blot图像分析结果显示:ISO各实验组大鼠左心室心肌组织中的ILK蛋白表达带均强于对照组(P<0.01),7、28和56 d组间比较差异有统计学意义(P<0.05)。结论 ILK与心肌肥厚的发生和发展有关,心肌肥大越重,ILK含量增加越高。     

卡托普利对实验性腹主动脉狭窄小鼠左心室肥厚的影响

目的 进一步证实实验性腹主动脉狭窄大鼠左心室肥厚及卡托普利的作用。方法 采用实验性腹主动脉银夹狭窄大鼠模型，观察左心室重量指数，放免测定血浆血管紧张素Ⅱ及左心室心肌局部ＡｎｇⅡ。结果 模型组ＬＶＭＩ，血浆ＡｎｇⅡ，左心室心肌ＡｎｇⅡ水平明显高于假手术组；卡托普利组ＬＶＭＩ，血浆ＡｎｇⅡ，左心室心肌ＡｎｇⅡ，左心室明显下降。     

心肌肥厚大鼠心肌组织中5-羟色胺及血管紧张素-Ⅱ含量的变化

目的：观察大鼠发生心肌肥厚时心肌组织中5-羟色胺（5-HT）及血管紧张素-Ⅱ（Ang-Ⅱ）含量的变化，探讨5-HT、Ang-Ⅱ与心肌肥厚发生的关系。方法：采用腹主动脉缩窄法建立压力超负荷心肌肥厚模型；腹腔注射甲状腺素法建立体液性心肌肥厚模型；荧光分光光度法和放射免疫分析法测定5-HT及Ang-Ⅱ含量。结果：大鼠腹主动脉缩窄后8周，心肌肥厚明显，分别于主动脉缩窄后4-8周内处死动物，发现心肌肥厚程度逐渐加重；心肌组中5-HT及Ang-Ⅱ含量也逐渐增加，并与肥厚程度呈正相关。腹腔注射甲状腺素2周后出现心肌肥厚，4周时症状加剧；于2、3、4周时处死动物，发现肥厚心肌组织中5-HT和Ang-Ⅱ含量均显著增加。结论：提示5-HT与心肌肥厚的形成有关，二者之间的相互关系尚待进一步研究。     

高交感活性诱导的大鼠心肌损伤模型中氧化应激的受体调控机制*

 目的：研究高交感活性诱发大鼠心肌损伤的氧化应激受体调控机制。方法：Sprague-Dawley (SD)大鼠随机分为对照组、模型组、普萘洛尔（Pro) 组、哌唑嗪(Praz)组、普萘洛尔+哌唑嗪 (Pro+Praz) 组、维生素E(VE)组及普萘洛尔+哌唑嗪+维生素E (Pro+Praz+VE) 组,除对照组外其余各组均腹腔注射去甲肾上腺素(NE) 复制高交感活性引起的心肌损伤模型,同时灌胃给予相应药物,连续给药16 d,期间监测各组动物体重的变化。16 d后进行心室重构指标（心指数和羟脯氨酸含量）、病理组织学检查、氧化/抗氧化指标（MDA、SOD、CAT、GSH-Px和T-AOC）和能量代谢指标（Na+-K+ATPase和Ca2+-Mg2+ATPase）分析。结果：从第9天开始,模型组动物体重与对照组的比较差异有统计学意义（P<0.05）,心指数和左心室肥厚明显增加,氧化/抗氧化和能量代谢障碍;Pro、Praz、Pro+Praz和VE各组均出现不同程度的动物体重、心指数、左心室肥厚和氧化/抗氧化失衡的改善;Pro、Praz和Pro+Praz能明显升高左心室Na+-K+ATPase和Ca2+-Mg2+ATPase的活性,Pro+Praz作用最明显（P<0.05）。结论：肾上腺素受体依赖是高交感活性诱导心肌氧化应激损伤的重要途径。     

血管紧张素-(1-7)对心肌肥厚的影响及其与细胞外信号调节激酶的关系

目的：探讨血管紧张素-(1-7)［Ang-(1-7)］对压力负荷性心肌肥厚的影响及其与细胞外信号调节激酶1/2(ERK1/2)的关系。 方法： 采用腹主动脉缩窄术复制心脏压力负荷增高大鼠模型。75只SD大鼠随机分为假手术组、模型对照组、Ang-(1-7)治疗组。在腹主动脉缩窄术后1 d开始，Ang-(1-7)治疗组大鼠，经置入式微量泵持续颈静脉给予Ang-(1-7) (25 μg·kg-1·h-1)；假手术组及模型对照组经微量泵只给予同量的生理盐水。各组分别于术后1周、术后4周处死部分大鼠，检测左心室重量/体重比、血浆及心肌血管紧张素Ⅱ浓度，并采用免疫印迹方法检测大鼠心肌中磷酸化ERK1/2(p-ERK1/2)表达水平。 结果： 术后1周和4周，腹主动脉缩窄均导致心肌血管紧张素Ⅱ浓度升高、左心室重量/体重比增加，也导致了心肌中p-ERK1/2表达增高；血管紧张素-(1-7)治疗未改变腹主动脉缩窄对心肌血管紧张素Ⅱ浓度的影响，但能明显减轻腹主动脉缩窄所诱导增高的左心室重量/体重比和心肌中p-ERK1/2表达水平。 结论： 外源性Ang-(1-7)可减轻压力负荷增高所致的心肌肥厚，这一作用可能与它抑制心肌p-ERK1/2表达有关。     

整合素β1在异丙肾上腺素诱导大鼠心肌肥厚组织中的表达

目的　观察心肌肥厚大鼠心肌组织中整合素β1的表达变化。 方法　在大鼠背部皮下分别注射7 d、28 d和56 d异丙肾上腺素（ISO）,判定心肌肥厚指标,利用免疫组织化学和免疫印迹技术,观察整合素β1在肥厚左心室肌中的表达。 结果　免疫组化和Western blot结果显示,整合素β1主要表达于心肌细胞膜。与对照组相比,实验各组大鼠的心肌组织的整合素β1表达明显（P<0.05）。7 d、28 d和56 d各组间相比其表达含量逐渐增强。 结论　在心肌肥厚状态下,心肌细胞中的整合素β1表达增高,随着心肌肥大的进展其表达逐渐增加,提示整合素β1在心肌肥厚发生发展起重要作用。     

静脉注射SCAD重组腺病毒减轻自发性高血压大鼠心肌肥厚和纤维化

目的:研究短链酰基辅酶A脱氢酶(short-chain acyl-coenzyme A dehydrogenase,SCAD)重组腺病毒(SCAD recombinant adenovirus,Ad-SCAD)对自发性高血压大鼠(spontaneously hypertensive rats,SHR)心肌肥厚和纤维化的影响。方法:以12周龄SHR为心肌肥厚和纤维化模型,以Wistar大鼠为正常对照,尾静脉注射Ad-SCAD治疗8周。将大鼠为Wistar+Ad-GFP组、SHR+Ad-GFP组、Wistar+Ad-SCAD组和SHR+Ad-SCAD组。观察各组大鼠血压、左室重量指数、超声心动图数据和心脏形态学变化;检测左心室羟脯氨酸含量、SCAD蛋白和mRNA表达、心肌肥厚和纤维化标志物的mRNA表达、SCAD酶活性、ATP含量及游离脂肪酸含量的变化。结果:与Wistar+AdGFP组相比,SHR+Ad-GFP组出现明显的病理性心肌肥厚和纤维化。与SHR+Ad-GFP组相比,SHR+Ad-SCAD组SCAD蛋白和mRNA表达水平及酶活性均显著升高,左心室前、后壁肥厚显著减轻,左心室内径显著增大,心脏舒张功能改善,心肌肥厚显著减轻,胶原沉积明显减少,心肌纤维化明显减轻,心肌组织的ATP含量明显升高,游离脂肪酸含量显著降低。结论:尾静脉注射Ad-SCAD能显著减轻SHR心肌肥厚和纤维化。     

异丙肾上腺素诱导小鼠心肌肥厚模型的方法优化

目的对应用异丙肾上腺素(isoproterenol,ISO)诱导小鼠心肌肥厚模型的方法进行进一步的优化。方法小鼠皮下注射剂量为7mg/kg的ISO,每日注射1次,连续注射1周。应用心重体重比,左心室重体重比,心肌细胞横截面积等指标来验证心肌肥厚模型的构建情况。应用切片HE染色方法来观察小鼠心肌细胞的形态学改变。结果实验组与对照组相比,心重体重比,左心室重体重比,心肌细胞横截面积均增加(P0.05)。与对照组相比,实验组心肌细胞横截面的直径增大,细胞间质增宽,细胞核变形。结论皮下注射ISO 1周,成功构建小鼠心肌肥厚模型,该方法更加简单,经济,科学,快速。为后续实验进行更加深入的研究提供了条件。     

Prevention of exercise-induced cardiac hypertrophy in rats by chemical sympathectomy (guanethidine treatment)

The effect of 'chemical sympathectomy', produced by daily intraperitoneal injections of guanethidine sulphate for six weeks, was studied in sedentary rats and in rats chronically exercised by swimming. The guanethidine-treatment itself caused the following changes. There was a reduction in the rate of weight gain resulting in a 7% lower final body weight. Organ content of noradrenaline was decreased by 90% in spleen and submandibular glands and by 83% in the heart. Urinary excretion of noradrenaline was also decreased, but to a lesser degree, both during rest (45% lower) and after acute exercise (46% lower), while the urinary excretion of adrenaline was no different from that of controls. There was a compensatory adrenal hypertrophy in the guanethidine-treated rats, with a significant increase in adrenal catecholamine levels that was more pronounced for noradrenaline (+45%) than for adrenaline (+11%). Chronic physical exercise produced the expected degree of cardiac hypertrophy in untreated rats, but this adaptive cardiac hypertrophy was completely absent in the exercised guanethidine-treated rats. The results indicate, firstly that a good degree of chemical sympathectomy was obtained and that the persistence of a considerable urinary excretion of catecholamines in the guanethidine-treated rats was due to a compensatory increase in the secretory activity of the adrenal medulla. Secondly, it is suggested that the adaptive cardiac hypertrophy produced by chronic exercise is not caused by a direct effect of the increased work load on the cardiac muscle cell, but is instead mediated by release of a trophic factor from cardiac sympathetic nerves, probably noradrenaline itself but possibly a secretory protein.     

肾交感神经去除术对心肌肥厚和心肌纤维化的影响

 目的:观察肾交感神经去除术（renal sympathetic denervation, RDN）对心肌肥厚和心肌纤维化的影响,并探讨其可能机制。方法:选用12周龄的健康SD雄性大鼠60只,随机分为假手术组、假手术+RDN组、主动脉缩窄组、主动脉缩窄+RDN组,8周后用介入生理记录仪检测血流动力学和心功能指标,HE染色、苦味酸-天狼星红染色分别观察心肌肥厚和心肌纤维化情况,放射免疫分析法测量血浆肾上腺素浓度、肾素活性、血管紧张素II浓度及心脏血管紧张素II含量。结果:与主动脉缩窄组相比,RDN可显著改善主动脉缩窄大鼠心脏舒张功能［左室舒张末期压力（LVEDP）：(8.03±1.66) mmHg vs(15.77±2.14) mmHg;等容舒张期左室压力下降最大速率（-dp/dt）：(7 793±587) mmHg/s vs(6 353±475) mmHg/s;P＜0.01］、防止其心肌肥厚和纤维化［左心室重量指数：3.340±0.121 vs4.244±0.102;心肌细胞面积：(332.9±28.9) μm2 vs(401.6±33.2) μm2;胶原容积分数：7.76%±0.85% vs12.48%±1.82%;P＜0.01］。然而,RDN不能降低主动脉缩窄大鼠的血压（P＞0.05）。RDN导致主动脉缩窄大鼠的血浆肾上腺素浓度、肾素活性、血管紧张素II浓度及心脏血管紧张素II含量均明显减少（P＜0.01）。结论: RDN可以通过降低交感和肾素-血管紧张素系统活性直接抑制心肌肥厚和心肌纤维化,从而改善心脏功能。     

Brief and repeated noise exposure produces different morphological and biochemical effects in noradrenaline and adrenaline cells of adrenal medulla

Exposure to stressful stimuli is known to activate the peripheral sympathetic nervous system and the adrenal gland. In this study, we evaluated the effects of single or repeated bouts of exposure to a readily measurable stressful stimulus (loud noise) on the catecholamine content and ultrastructure of the rat adrenal medulla. In particular, we measured tissue levels of dopamine, noradrenaline, adrenaline and metabolites. In parallel studies, we evaluated the fine ultrastructure of catecholamine cells, including a detailed study of catecholamine granules and a morphometric analysis of adrenaline and noradrenaline medullary cells. Animals were exposed either to a single (6 h) session of loud (100 dBA) noise, or to this noise stimulus repeated every day for 21 consecutive days. There was a marked correlation between biochemical indexes of catecholamine activity and the ultrastructural morphometry of specific catecholamine granules. Exposure to loud noise for 6 h induced a parallel increase in dopamine, noradrenaline, adrenaline and their metabolites, a polarization and an increased numerical density of noradrenaline and adrenaline granules in the cells. After repeated noise exposure, noradrenaline levels were significantly higher than in controls, and adrenaline decreased significantly. In addition, adrenaline cells also exhibited ultrastructural alterations consisting of wide homogeneous cytoplasmic areas and large, pale vesicles.     

Catecholamine synthesis inhibitors increase pineal adrenaline content by stimulating adrenal medullary activity

Estimation of noradrenaline and adrenaline utilization in the pineal gland of female rats was attempted using inhibitors of the enzymes that catalyse the catecholamine biosynthetic pathway. Treatment with FLA63, an inhibitor of dopamine beta-hydroxylase (10 mg/kg, 2 h before killing), induced depletion of noradrenaline and adrenaline in the preoptic area and median eminence (sites, respectively, inside and outside the blood-brain barrier) but, paradoxically, resulted in a significant increase (+77%) in the pineal content of adrenaline without affecting that of noradrenaline. Treatment with LY134046, an inhibitor of phenylethanolamine N-methyltransferase (40 mg/kg, 5 and 2 h before killing), induced depletion of adrenaline in the preoptic area and median eminence but, again, resulted in a paradoxical and large increase in pineal adrenaline (+224%); this increase was prevented by prior adrenalectomy. Blood samples taken from free-moving rats fitted with intravenous and intraperitoneal cannulae revealed a marked increase in plasma levels of adrenaline after each injection of LY134046. These results suggest that the adrenal medulla is the primary source for the increase in pineal adrenaline seen after administration of the enzyme inhibitors. The precise site of uptake and the biological implications of this phenomenon remain to be elucidated. Nevertheless, interpretation of in vivo experiments involving these catecholamine synthesis inhibitors should take this adrenal response into account.     

Development of SHR hypertension and cardiac hypertrophy during prolonged beta blockade.

Spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were treated with beta-adrenergic receptor inhibiting drugs (either propranolol or timolol) from conception until 12 weeks of age to determine if this therapy would alter the development of systemic hypertension or left ventricular hypertrophy. Therapy (propranolol or timolol, 500 mg/liter drinking water) was initiated with breeding parents and continued throughout the pregnancy, nursing, and postweaning periods. Although the heart rates of beta-adrenergic receptor inhibited WKY and SHR rats were consistently reduced with respect to their respective tap-water controls, this therapy did not alter body growth. Hemodynamic studies demonstrated reduced central venous pressure, cardiac index, and maximum acceleration of aortic flow in the beta-adrenergic inhibited rats. In spite of these findings, the arterial pressure of the treated rats and the degree of left ventricular hypertrophy of the SHR were unaltered by treatment. Thus, administration of the beta-adrenergic receptor blocking agents, propranolol or timolol, from conception through the developmental stage of SHR hypertension, failed to alter either the progressive rise in arterial pressure or the development of hypertensive vascular disease and left ventricular hypertrophy.     

Renin angiotensin system and cardiac hypertrophy after sinoaortic denervation in rats

OBJECTIVE:

The aim of this study was to evaluate the role of angiotensin I, II and 1–7 on left ventricular hypertrophy of Wistar and spontaneously hypertensive rats submitted to sinoaortic denervation.

METHODS:

Ten weeks after sinoaortic denervation, hemodynamic and morphofunctional parameters were analyzed, and the left ventricle was dissected for biochemical analyses.

RESULTS:

Hypertensive groups (controls and denervated) showed an increase on mean blood pressure compared with normotensive ones (controls and denervated). Blood pressure variability was higher in denervated groups than in their respective controls. Left ventricular mass and collagen content were increased in the normotensive denervated and in both spontaneously hypertensive groups compared with Wistar controls. Both hypertensive groups presented a higher concentration of angiotensin II than Wistar controls, whereas angiotensin 1–7 concentration was decreased in the hypertensive denervated group in relation to the Wistar groups. There was no difference in angiotensin I concentration among groups.

CONCLUSION:

Our results suggest that not only blood pressure variability and reduced baroreflex sensitivity but also elevated levels of angiotensin II and a reduced concentration of angiotensin 1–7 may contribute to the development of left ventricular hypertrophy. These data indicate that baroreflex dysfunction associated with changes in the renin angiotensin system may be predictive factors of left ventricular hypertrophy and cardiac failure.     

Administration of pigment epithelium-derived factor inhibits left ventricular remodeling and improves cardiac function in rats with acute myocardial infarction

Oxidative stress and inflammation are involved in cardiac remodeling after acute myocardial infarction (AMI). We have found that pigment epithelium-derived factor (PEDF) inhibits vascular inflammation through its anti-oxidative properties. However, effects of PEDF on cardiac remodeling after AMI remain unknown. We investigated whether PEDF could inhibit left ventricular remodeling and improve cardiac function in rats with AMI. AMI was induced in 8-week-old Sprague-Dawley rats by ligation of the left ascending coronary artery. Rats were treated intravenously with vehicle or 10 μg PEDF/100 g b.wt. every day for up to 2 weeks after AMI. Each rat was followed until 16 weeks of age. PEDF levels in infarcted areas and serum were significantly decreased at 1 week after AMI and remained low during the observational periods. PEDF administration inhibited apoptotic cell death and oxidative stress generation around the infarcted areas at 2 and 8 weeks after AMI. Further, PEDF injection suppressed cardiac fibrosis by reducing transforming growth factor-β and type III collagen expression, improved left ventricular ejection fraction, ameliorated diastolic dysfunction, and inhibited the increase in left ventricular mass index at 8 weeks after AMI. The present study demonstrated that PEDF could inhibit tissue remodeling and improve cardiac function in AMI rats. Substitution of PEDF may be a novel therapeutic strategy for cardiac remodeling after AMI.     

Reversal of cardiac hypertrophy in renal hypertensive rats: medical vs. surgical therapy

Cardiac hypertrophy consequent to renovascular hypertension was investigated in two-kidney one-clip Goldblatt rats. Ventricular weight in renal hypertensive rats correlated closely with level of arterial pressure (r = 0.93, P less than 0.001). DNA, RNA and hydroxyproline contents of the hypertrophied hearts were higher than sham control, but there was no significant change in myocardial concentration of any of them. Surgical treatment (removal of clipped kidney) as well as medical therapy (inhibition of converting enzyme with orally administered captopril, 150 mg/l drinking water) led to reduction of ventricular weight (2.70 +/- 0.01 and 2.78 +/- 0.06, respectively, vs. 3.4 +/- 0.05 mg/g in controls, P less than 0.01 for both). Reduction of cardiac weight was associated with increase in both myocardial concentration and content of hydroxyproline in surgically treated rats and in medically treated animals. Ventricular catecholamine concentration was increased after nephrectomy but was unchanged by captopril treatment.     

压力超负荷对大鼠左室心肌肌型LIM蛋白mRNA和蛋白表达的影响

目的:了解压力超负荷大鼠左室肥厚心肌肌型LIM蛋白(MLP)mRNA和蛋白水平的变化, 探讨病理性左室肥厚心肌是否存在细胞骨架蛋白的缺失。方法:观察大鼠腹主动脉缩窄术后1、4、8、16周各组血流动力学参数、心室肥厚指数、MLPmRNA表达和蛋白水平的变化。结果:腹主动脉缩窄术后4周左室肥厚指数较术后1周组明显增加(P＜0.05), 术后8周组左室心肌MLPmRNA的表达较术后1、4周组明显下降(P＜0.05), 但各组左室心肌MLP蛋白水平差异无显著(P＞0.05)。结论:在病理性左室肥厚心肌出现明显心力衰竭前, MLP转录水平下调, 而MLP蛋白水平无明显改变。提示MLP作为心肌细胞骨架的基础, 对维持肥厚左室心肌的收缩功能起重要作用。     

Effects of graded exercise on blood pressure,heart rate,and plasma hormones in cardiac transplant recipients before and during antihypertensive therapy

Summary The effects of graded supine ergometry on blood pressure, heart rate, and plasma hormones were studied in 14 hypertensive heart transplant recipients before and after 2 weeks and 6 months of enlapril (20 mg/day) plus furosemide (20–80 mg/day) alone or combined with verapamil (120–360 mg/day). Each time, measurements were obtained at rest and at 25 and 50 W exercise. Anti-hypertensive therapy normalized blood pressure, while heart rate and the blood pressure response to exercise remained unaltered. Pretreatment resting plasma renin activity and catecholamine levels were normal, while atrial natriuretic factor and cyclic guanosine monophosphate concentrations were elevated. All hormones increased significantly with exercise. During treatment, plasma renin activity increased and atrial natriuretic factor and cyclic guanosine monosphosphate levels decreased significantly, with a blunted exercise response; concentration of catecholamines increased significantly, with augmented exercise response. Thus, the chosen regimen allowed effective, lasting BP control in hypertensive transplant patients but was associated with significant changes in plasma hormones. Whereas the rise in plasma renin activity may be attributed to converting enzyme inhibition, the decreases in atrial natriuretic factor and cyclic guanosine monophosphate and increases in catecholamine levels seem to indicate marked changes in resting and particularly exercise hemodynamics during antihypertensive therapy.Abbreviations A adrenaline - ANF atrial natriuretic factor - BP blood pressure - CE converting enzyme - cGMP cyclic guanosine monophosphate - ECG electrocardiogram - LV left ventricular - NA noradrenaline - PRA plasma renin activity - RV right ventricular Supported by research grants 86.015.1 and 86.015.2 of the Wilhelm Sander Foundation and grant DFG Ge-399/3-3 of the Deutsche Forschungsgemeinschaft