Enhanced psychophysiological signs of attention after angiotensin-converting enzyme inhibition by captopril

Complementary to its essential role in the central nervous control of cardiovascular activity, the neuropeptide angiotensin 11 may regulate attentional processes. The present study evaluated central nervous, cardiovascular, and sympathetic indicators of attention after inhibition of angiotensin II synthesis by captopril (50 mg vs. placebo) in 14 men. Event-related potentials (ERPs) and stimulus-related electroencephalographic (EEG) activity were recorded while the subject performed an auditory oddball task. Captopril increased both the N1-P2 component of the ERP (p < .05) and – following the first tone of the task – the EEG desynchronization in the lower alpha frequency band (p < .05). Although blood pressure remained unchanged, heart rate was lowered (p < .05) and plasma norepinephrine concentrations increased (p < .01) after captpril. The effects suggest that inhibition of angiotensin II synthesis enhances an attentional state typically present during sensory intake.     

The effects of angiotensin-converting enzyme inhibitors on peritoneal protein loss and solute transport in peritoneal dialysis patients

OBJECTIVE:

The objective of this study was to examine the effects of angiotensin-converting enzyme inhibitors on peritoneal membrane transport, peritoneal protein loss, and proteinuria in peritoneal dialysis patients.

METHODS:

Fifty-four peritoneal dialysis patients were included in the study. The patients were divided into two groups. Group 1 (n = 34) was treated with angiotensin-converting enzyme inhibitors. Group 2 (n = 20) did not receive any antihypertensive drugs during the entire follow-up. Eleven patients were excluded from the study thereafter. Thus, a total of 30 patients in Group 1 and 13 patients in Group 2 completed the study. We observed the patients for six months. Group 1 patients received maximal doses of angiotensin-converting enzyme inhibitors for six months. Parameters at the beginning of study and at the end of six months were evaluated. ClinicalTrial.gov: {"type":"clinical-trial","attrs":{"text":"NCT01575652","term_id":"NCT01575652"}}NCT01575652.

RESULTS:

At the end of six months, total peritoneal protein loss in 24-hour dialysate effluent was significantly decreased in Group 1, whereas it was increased in Group 2. Compared to the baseline level, peritoneal albumin loss in 24-hour dialysate effluent and 4-hour D/P creatinine were significantly increased in Group 2 but were not significantly changed in Group 1. A covariance analysis between the groups revealed a significant difference only in the decreased amount of total protein loss in 24-hour dialysate. Proteinuria was decreased significantly in Group 1.

CONCLUSION:

This study suggests that angiotensin-converting enzyme inhibitors reduce peritoneal protein loss and small-solute transport and effectively protect peritoneal membrane transport in peritoneal dialysis patients.     

Changes in angiotensin-converting enzyme activity and angiotensin I level in asthmatic and healthy children after submaximal physical work

The changes in angiotensin-converting enzyme activity and serum angiotensin I levels have been studied in 16 controls subjected to submaximal physical work. Baseline (Pre-exercise) angiotensin I levels were identical in both groups. Physical exercise caused an elevation that was more marked in the asthmatic group than in the control group. The activity of serum angiotensin-converting enzyme differed in the two groups even before physical exercise, the asthmatic children having exhibited an activity level significantly lower than that of the healthy controls. after submaximal work, the enzyme activity increased in healthy subjects but decreased in asthmatic children.     

Effects of the new angiotensin-converting enzyme inhibitor,ramipril, in patients with essential hypertension

Summary The antihypertensive and hormonal effects of the new angiotensin-converting enzyme (ACE) inhibitor, ramipril, were assessed by means of a single-blind trial in ten unselected patients with mild-to-moderate essential hypertension. After a 2-week period on placebo, 5 mg ramipril was administered once daily for 2 weeks. Blood pressure returned to normal in five patients and decreased in the remaining patients, without significant changes in heart rate or orthostatic hypotension. A fall in blood pressure was apparent within 1–2 h of the first dose; the maximum decrease was reached at 4–6 h and a fall in pressure was still detectable after 24 h. At 24 h post dose angiotensin-converting enzyme activity was suppressed to 40% of the baseline. Blood pressures for the 10 h interval post dosing showed smooth through-the-day control with minimal peak/trough difference in lowering effect. The magnitude of the blood pressure decrement achieved with the inhibitor did not correlate with baseline renin levels or the rise in renin following treatment. No side-effects were noted during the 2-week observation period. The study demonstrates that ramipril, given in a once-daily regimen over a period of 2 weeks, is well tolerated and provides smooth and effective blood pressure control throughout the 24-h interval between doses.Abbreviations ACE angiotensin converting enzyme - PRA plasma renin activity     

Effects of angiotensin-converting enzyme inhibition and bradykinin peptides in rats with myocardial infarction

Background and objective: Angiotensin-converting enzyme (ACE) inhibitors have been reported to decrease myocardial remodeling and faciliate cardiac function improvement in the setting myocardial infarction by affecting bradykinin. The purpose of this study was to evaluate the combination effects of perindopril and bradykinin (BK) in rats with myocardial infarction. Methods: Wistar Rats underwent to left anterior descending (LAD) coronary artery ligation were allocated into MI group (n = 6); Perindopril group (n = 7); Perindopril + BK group (n = 7). An additional sham operation group (Sham group, n = 6) were also established. After 4 weeks, the left ventricle function, myocardial tissue morphology, myocardial collagen volume faction, infracted ventricular wall thickness, myocardial infarction area and neovascular formation were evaluated. Results: Combination treatment with perindopril and BK were showed significant improvement on LVEDV, LVEF and LVFS than MI group. Moreover, a significant improvement on LVEF was found in Perindopril + BK group than Perindopril group but not on LVEDV and LVFS between these two groups. Furthermore, neo-vessel density was significantly increased in Perindopril + BK group than other groups while no significant improvement on vessel density was found after the treatment of perindopril. In addition, myocardial infarction thickness improvement was found in Perindopril and group than MI group while combination treatment with perindopril and BK can significant improve the myocardial infarction thickness than perindopril only. Conclusions: Combination treatment with ACE inhibitor perindopril and BK can significantly improve the ventricle function in the rat model of myocardial infarction. Our data suggest BK can serve as adjuvant treatment in myocardial infarction treatment.     

血管紧张素转换酶抑制剂对损伤后动脉弹性蛋白酶的影响

目的：研究球囊导管损伤后早期血管紧张素转换酶抑制剂对动脉中膜弹性蛋白酶的影响。方法：12周雄性Wistar大鼠颈动脉和主动脉用球囊导管损伤,分成实验组和对照组,分别于术前2 d投与血管紧张素转换酶抑制剂（temocapril-HCl, 10 mg·kg^-1·d^-1）和溶剂,术后2、3、5和10 d处死。用原位杂交、免疫组织化学和酶活性测定研究弹性蛋白酶。结果：实验组动脉损伤10 d时的内膜面积与对照组相比明显被抑制（P<0.01）,实验组2、3和5 d弹性蛋白酶mRNA阳性细胞率、弹性蛋白酶阳性细胞率及其活性明显低于对照组（P<0.01, P<0.05）。结论：ACEI（temocapril-HCl）明显抑制损伤后动脉中膜平滑肌弹性蛋白酶表达和活性,提示弹性蛋白酶的表达与血管紧张素转换酶的作用有关。     

运动与苯那普利联合治疗对胰岛素抵抗的影响

目的：研究运动训练与血管紧张素转换酶抑制剂（ACEI）苯那普利联合或单独治疗对高脂饮食大鼠胰岛素抵抗（IR）的影响。方法：雄性Wistar大鼠36只，随机分为6组：正确对照（NC）组，正常运动（NE）组、高脂饮食（HF）组、高脂运动（EHF）组、高脂苯那普利（BHF）组和高脂、运动、苯那普利联合治疗（CHF）组。以葡萄糖-胰岛素耐量试验（G-InsTT）检测胰岛素敏感性，同时检测空腹、餐后血糖、血清FFA及空腹胰岛素浓度（FIns）。结果：HF组大鼠Fins水平明显高于NC组，G-InsTT中K值明显低于NC组（P<0.01）；而EHF组、BHF组、CHF组FIns水平均低于HF组，G-InsTT中K值明显高于HF组（P<0.01），尤以CHF组效果更显著。结论：长期高脂饮食导致的IR的发生，运动训练与苯那普利均明显减轻IR，二者联合应用优于单一治疗。     

血管紧张素转换酶2基因转染对人内皮细胞MIF表达的影响

目的：探讨重组血管紧张素转换酶2（ACE2）基因转染对体外培养的人血管内皮细胞中由血管紧张素（Ang）II诱导的巨噬细胞移动抑制因子（MIF）表达的影响。方法:克隆和构建含人ACE2基因全长的重组质粒（pACE2），并将之转染入人血管内皮细胞中。分别采用实时定量PCR和Western印迹技术检测转染细胞中的MIF mRNA与蛋白表达情况。结果: Ang Ⅱ（100 nmol/L）和Ang IV（100 nmol/L）刺激后均可诱导人血管内皮细胞中MIF mRNA及蛋白表达增加（P<0.01）。pACE2基因转染可明显抑制内皮细胞中由Ang II和Ang IV诱导的MIF mRNA和蛋白表达（P<0.05）。结论: ACE2基因过表达可明显抑制人内皮细胞中炎症介质MIF的表达，提示ACE2基因具有一定的抗炎症效应。通过调节ACE2基因的活性和表达，很可能为炎症相关疾病如动脉粥样硬化治疗提供新的策略。     

血管紧张素转换酶抑制剂抑制血管平滑肌细胞增殖的机制

目的: 探讨血管紧张素转换酶抑制剂(ACEI)抑制动脉平滑肌细胞增殖及向内膜迁徙的机理。方法: 球囊导管损伤Wistar大鼠颈总动脉, 实验组于术前2 d开始给与ACEI(temocapril-HCl 10 mg·kg^-1·d^-1), 术后2 d、3 d、5 d分批处死。用抗人PDGF-A、-B及其受体, 抗人MMP-1、MMP-9等抗体以ABC法行免疫染色。动脉组织行放射自显影乳剂原位酶谱分析。电镜下观察细胞质内小器官及细胞周围弹性、胶原纤维的密度。结果: 给ACEI后, PDGF及其受体、MMP-1、-9蛋白阳性细胞率及明胶酶活性显著降低, 并抑制了中膜平滑肌细胞的表型转换。结论: ACEI可能通过继发地抑制PDGFs、MMPs蛋白表达, 阻碍细胞表型转换, 从而阻止中膜平滑肌细胞增殖及向内膜迁徙。     

Autoradiography of angiotensin-converting enzyme in fixed and unfixed rat brain using the specific enzyme inhibitor [I]351A or a polyclonal antibody and [I]staphylococcal protein A

Angiotensin-converting enzyme (ACE, kininase II, EC 3.4.15.1) was visualized in unfixed rat brain sections by autoradiography after incubation with a polyclonal goat anti-rabbit lung converting-enzyme antibody and [¹²⁵I]protein A. Paraformaldehyde fixation interfered with the recognition of ACE by its antibody in brain nuclei but not in the choroid plexus. Conversely, incubation of brain sections with the specific ACE inhibitor [¹²⁵I]351A allowed ACE visualization in either unfixed and paraformaldehyde-fixed brain sections, since [¹²⁵I]351A binding was not affected by our fixation conditions. Our results indicate that ACE could be visualized in unfixed brain sections directly by incubation with the specific inhibitor [¹²⁵I]351A or indirectly by radioimmunohistochemistry and autoradiography. Different autoradiographic methods could be used to visualize and quantify ACE in unfixed or fixed tissues.     

The acute effects of exercise and glucose ingestion on circulating angiotensin-converting enzyme in humans

Angiotensin-converting enzyme (ACE) activity has been suggested as a determinant of some exercise phenotypes via some studies that have associated the ACE gene with exercise performance, although several studies provide conflicting evidence regarding the influence of the ACE gene. The relationships between ACE phenotype (ACE activity) and various exercise parameters should also be examined. An early step in this process is to determine whether common environmental stimuli such as exercise and diet have acute effects on ACE activity. In this study, the acute effects of aerobic exercise, resistance exercise and glucose ingestion on circulating ACE activity were examined. On three separate occasions, 20 healthy adult volunteers (9 female and 11 male) performed 20 min of submaximal cycle exercise at 70–80% of maximal heart rate, four sets of ten repetitions of unilateral leg extension resistance exercise at ten-repetition maximum load, or ingested 1 g kg^–1 glucose. Circulating ACE activity was assessed for 1 h after each intervention using a modified fluorometric method. Pre-intervention ACE activity remained remarkably stable across test days (difference 1.8%). Furthermore, there was no significant change in circulating ACE activity following any of the interventions (difference from pre-intervention values 6.8% when unadjusted for plasma volume changes, 4.5% when adjusted for plasma volume changes). These results suggest that acute exercise and glucose ingestion interventions as used here do not affect circulating ACE activity. These findings are an early step in illuminating the relationships between ACE activity and various exercise parameters.     

Comparion of serum angiotensin-converting enzyme in Graves' disease,toxic nodular goiter,and other thyroid conditions

Summary Angiotensin-converting enzyme (ACE) was measured in plasma of patients with Graves' disease and with toxic nodular goiter, as well as in their treated counterparts and in normal controls. A significant elevation of ACE levels and a positive correlation between ACE, thyroxine, and triiodothyronine levels was found in both groups of thyrotoxicosis. Parallel fluctuations of triiodothyronine and ACE levels, albeit with a certain lag of the latter, was observed in patients in whom multiple measurements were taken. ACE levels, which were also determined in hypothyroid patients and in patients with euthyroid goiter on suppression therapy, were in the same range as normal controls and as in treated thyrotoxic patients. We conclude that the pathogenesis of thyrotoxicosis does not play a role in ACE elevation but that increased thyroid hormone seems to induce elevation of ACE. ACE elevation in thyrotoxicosis may constitute an integral part of the reninangiotensin axis.Abbreviations ACE Angiotensin-converting enzyme - n.g. Nodular goiter - T₄ Thyroxine - T₃ Triiodothyronine     

Proximal tubular transport and urinary excretion of sodium after renal denervation in sodium depleted rats

The effect of unilateral renal denervation on renal handling of water, sodium and potassium was studied with clearance and micropuncture techniques in sodium depleted anaesthetized rats in the nondiuretic state. In clearance experiments renal denervation resulted in a +140 and +320% increase in urine flow and potassium excretion, but sodium excretion of innervated (I) and denervated (D) kidneys was similar (I: 12.0±2.0, D: 14.0±3.6 nM·min^–1·g^–1; NS). However, upon the loop diuretic furosemide (1 mg·kg^–1), a marked denervation natriuresis was observed (I: 2.8±0.9, D: 5.9±1.0 M·min^–1;P<0.05) and denervation diuresis and kaliuresis persisted, too (+95 and +60%, respectively). Micropuncture results revealed that fractional reabsorption of filtrate to late proximal puncture site was depressed by renal denervation from 62 to 49% while no change in time control rats was seen (64±2 vs. 64±1%; NS). In micropuncture experiments besides augmented urine flow (+82%) from D kidneys also a small denervation natriuresis was present (I: 21.6±6.4, D: 29.2±7.0 nM·min^–1;P<0.05). It is concluded that the lack or marked attenuation of denervation natriuresis in sodium depleted rats were the result of an almost complete compensatory distal reabsorption of the excess sodium (but not of water and potassium) leaving the proximal tubule after denervation. The distal adaptive response can be overcome by furosemide.     

Relation between angiotensin-converting enzyme II genotype and atrial fibrillation in Japanese patients with hypertrophic cardiomyopathy

Atrial fibrillation (AF) occurs in about 20% of patients with hypertrophic cardiomyopathy (HCM). HCM patients with AF have an increased risk for clinical decline and thromboembolism. In addition, AF is known to be associated with the atrial renin-angiotensin system (RAS). However, the relation between AF and the RAS in HCM has not been investigated. We genotyped the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in 138 HCM patients (26 with AF, 112 with sinus rhythm). Distribution of the ACE genotypes (DD, ID, and II) among the total HCM patients was 15%, 46%, and 38%. AF was documented in 3 patients with the DD genotype, 7 with the ID genotype, and 16 with the II genotype (P < 0.03 vs. sinus rhythm group). The odds of AF were 3.2-fold greater in patients with the II genotype than in those with the other genotypes (P = 0.009, 95% confidence interval = 1.3–7.8). Kaplan-Meier curves examining the time to the first documented AF event showed a significant difference between genotypes during the follow-up period (mean 116 months, P < 0.05). These findings suggest that the II genotype of the ACE gene is a significant risk factor for AF in patients with HCM. Received: December 10, 2001 / Accepted: January 25, 2002     

The serum angiotensin-converting enzyme and angiotensin II response to altered posture and acute exercise, and the influence of ACE genotype

The deletion (D) rather than insertion (I) allele of the angiotensin-converting enzyme (ACE) gene is associated with greater ACE activity. We examined: (1) the influence of posture change (recumbent to seated) and acute exercise on serum ACE and angiotensin II (Ang II) activity; (2) the relationship between ACE and Ang II levels; and (3) the influence of ACE genotype on changes in ACE and Ang II levels with posture and exercise. Recreationally active young male Caucasians (10 each of II, ID and DD genotypes) rested for 35 min supine then 15 min upright, took 20 min bicycle ergometric exercise at 70% maximum oxygen uptake, then rested for 40 min. Samples were taken throughout for ACE activity and Ang II levels. Supine ACE levels were dependent upon ACE genotype [24.8 (5.7), 26.9 (4.5), 45.5 (6.4) nmol His-Leu ml^–1 min^–1; II, ID, DD, respectively; P<0.00005] and thereafter. ACE activity rose with assumption of a seated posture [from 32.4 (10.9) nmol His-Leu ml^–1 min^–1 to 35.0 (11.5) nmol His-Leu ml^–1 min^–1, P<0.00001], the absolute rise being independent of genotype [3.22 (1.92), 1.6 (1.6), 2.4 (2.3) nmol His-Leu ml^–1 min^–1; II, ID, DD; P=0.22], unlike percentage change [12.8 (6.8), 5.6 (5.5), 5.3 (5.0)%; II, ID, DD; P<0.01, and P=0.004 for II vs presence of the D allele]. A further genotype-independent rise occurred with exercise [+2.9 (3.7) units, P<0.0003]. An associated rise in Ang II levels [30.3 (15.9), or 2587.9 (489.76)%, P<0.00001] was independent of ACE genotype or activity. Upright posture increases ACE activity, and this may be influenced by ACE genotype. ACE activity and Ang II levels rise independently with exercise in a non-genotype-dependent fashion.     

New insights into the role of angiotensin-converting enzyme obtained from the analysis of genetically modified mice

Angiotensin-converting enzyme (ACE) has been well-recognized for its role in blood pressure regulation. ACE is made by many tissues, though it is most abundantly expressed on the luminal surface of vascular endothelium. ACE knockout mice show a profound phenotype with low blood pressure, but also with hemopoietic and developmental defects, which complicates understanding the biological functions of ACE in individual tissue types. Using a promoter-swapping strategy, several mouse lines with unique ACE tissue expression patterns were studied. These include mice with ACE expression in the liver (ACE 3/3), the heart (ACE 8/8), and macrophages (ACE 10/10). We also investigated mice with a selective inactivation of either the N- or C-terminal ACE catalytic domain. Our studies indicate that ACE plays a role in many other physiologic processes beyond simple blood pressure control.     

依那普利对自发性高血压大鼠心肌ACE和ACE2表达的影响

 目的 观察自发性高血压大鼠(spontaneously hypertensive rats, SHR)心肌的血管紧张素转换酶(angiotensin-converting enzyme, ACE)和ACE2的表达,以及依那普利干预的影响。方法 将15只SHR随机分为2组：SHR对照组(n=7)和依那普利组(n=8),分别给以安慰剂、依那普利15mg.kg-1.d-1灌胃干预4周。干预结束后处死大鼠,分离左心室,行RT-PCR、western blot蛋白质免疫印迹检测。同步取10只WKY大鼠作为正常血压对照组。结果SHR心肌的ACE的mRNA和蛋白质的表达都显著高于)WKY组(1.68±0.34 vs 0.33±0.12, P＜0.05;1.21±0.14 vs 0.71±0.11, P＜0.05),而ACE2 的mRNA和蛋白质表达皆明显低于WKY组(0.50±0.15 vs 1.16±0.24, P＜0.05; 0.71±0.24 vs 1.22±0.14, P＜0.05)。依那普利明显降低ACE的mRNA和蛋白质表达(0.44±0.19 vs 1.68±0.34, P＜0.01; 0.87±0.13 vs 1.21±0.14, P＜0.05),提升ACE2的mRNA表达(1.77±0.49 vs 0.50±0.15, P＜0.05),对ACE2的蛋白表达无明显影响(0.42±0.22 vs 0.71±0.24, P＞0.05)。结论 SHR心肌ACE明显升高,ACE2显著降低,有利于血压上调。依那普利能降低ACE,提升ACE2,可能是血管紧张素转换酶抑制剂(angiotensin-converting enzyme inhibitors, ACEI)的降压机制之一。     

贝那普利对环孢素A慢性肾毒性的防护作用

目的 探讨贝那普利对环孢素A(CsA)慢性肾毒性的防护机理.方法 选雄性大鼠30只,随机分为3组,3组均给予低盐饮食.A组为CsA溶剂(橄榄油)对照组;B组为CsA组;C组为CsA加贝那普利.观察给药28 d后各组大鼠血浆肾素活性(PRA)、血管紧张素Ⅱ(AngⅡ)及醛固酮(ALD)水平的变化,并对肾组织进行组织学观察和免疫组织化学检测,观察贝那普利对上述改变的防护作用.结果 ①CsA可引起大鼠血浆PRA、AngⅡ水平明显升高,而贝那普利对大鼠PRA、AngⅡ水平的升高有明显的抑制作用;血浆醛固酮水平,A组和B组之间差异无显著性(P＞0.05),而贝那普利组醛固酮水平明显下降.②CsA能导致肾间质纤维化和小动脉病变,诱导大鼠肾内转化生长因子-β1(TGF-β1)的高表达,贝那普利能减轻上述改变.结论 CsA能激活肾素-血管紧张素系统(RAS),使大鼠肾内TGF-β1高表达;贝那普利能阻断RAS系统,尤其是能降低AngⅡ水平,减轻CsA引起的肾间质纤维化,使大鼠肾内TGF-β1表达下降.     

清醒山羊缺氧时的颅内动力学改变及速尿的影响

作者采用清醒山羊,在给予少量水负荷条件下,观察了急性低压缺氧时的颅内动力学改变及速尿的影响。结果提示:缺氧(模拟4000m高原历时2小时)可使脑血流量(CBF)、颅内平均压(MICP)和脑含水量均明显增加,颅内顺应性明显降低。注入速尿后,相同缺氧条件下的上述各参数均未出现明显改变。     

Association of essential hypertension in elderly Japanese with I/D polymorphism of the angiotensin-converting enzyme (ACE) gene

Recent evidence suggests that an insertion/deletion (I/D) polymorphism of the gene encoding angiotensin-converting enzyme (ACE) is associated with myocardial infarction and related cardiovascular diseases. We investigated a possible association of the ACE polymorphism with essential hypertension in a total of 263 cases/controls from among the elderly (age, over 70 years) and middle-aged (age between 30 and 60 years) Japanese population. The frequency of the I/I homozygote was significantly higher in hypertensive subjects than in controls in the elderly age group (33/57 vs 16/46; P = 0.02), but no association was observed in the middle-aged group (25/75 vs 26/85; P = 0.71). Similarly, having at least one insertion allele was associated with essential hypertension in the elderly age group (83/114 vs 46/92 in controls; P = 0.001), but not in the middle-aged group (78/150 vs 94/170; P = 0.524). These data suggest that genetic variation at the ACE locus may be associated with some determinants for blood pressure in elderly persons, and imply the involvement of the ACE insertion/deletion polymorphism in the etiology of age-related essential hypertension in the Japanese population. Received: April 18, 2000 / Accepted: July 25, 2000