血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂抑制胃癌血管生成

目的建立人胃癌裸鼠移植瘤模型，观察血管紧张素转换酶抑制剂（ACEI）及血管紧张素Ⅱ受体拮抗剂（ARB）对胃癌生长和血管生成的影响。方法设立对照组、ACEI组（又分为培哚普利组和卡托普利组）、ARB组（又分为氯沙坦组和缬沙坦组），定期观察各组肿瘤生长情况并测量肿瘤体积，3周后取出肿瘤标本，采用免疫组化测定各组的基质金属蛋白酶7（MMP-7）、血管内皮生长因子（VEGF）的表达和癌周微血管密度（MVD）。结果ACEI组和ARB组移植瘤体积与对照组相比．均明显受到抑制（P〈0．011。ACEI组和ARB组肿瘤组织中的VEGF和MVD与对照组比较，均显著降低（P〈0．05和P〈0．01）。ACEI组对MMP-7的表达具有抑制作用（P〈0．05）；而ARB对MMP-7无显著抑制作用。结论ACEI和ARB能明显抑制人胃癌裸鼠移植瘤的生长以及新生血管的形成。     

雌鼠膀胱血管紧张素系统的研究——注射血管紧张素I及血管紧张素转换酶抑制剂依那普利的反应

膀胱存在局部肾素 血管紧张素系统 ,目前对它很少了解。间质性膀胱炎是一种原因不明的疾病 ,已有证据表明其发病与膀胱内的肾素 血管紧张素系统密切相关。临床上男女发病比例 1∶10 ,在女性经期症状加重 ,而在孕期症状改善。肾素 血管紧张素与生殖功能相关 ,女性呈周期性 ,妊娠时增高。因为没有可靠的动物间质性膀胱炎模型 ,作者只能通过观察雌性大鼠在发情期、非发情期、孕期对注射依那普利 (肾素 血管紧张素Ⅰ和肾素 血管紧张素转换酶抑制剂 )的反应来判断临床结果。作者发现 :孕期中膀胱内平均ＡＮＧⅠ和ＡＮＧⅡ浓度明显高于血液中。注…     

慢性肾脏病应该使用血管紧张素转换酶抑制剂

美国的预防、发现、评估、治疗高血压全国委员会的第6次报告(JNC-Ⅵ)、2001年美国糖尿病协会(ADA)的临床实践指南以及一些荟萃分析的结果均表明：血管紧张素转换酶抑制剂(ACEI)和血管紧张素Ⅱ受体拮抗剂(ARB)可以减缓慢性肾脏病的进展。这两种药物除了可以降低血压，还可以降低肾小球毛细血管压和减少蛋白的滤过，减轻血     

血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂在IgA肾病中的应用

血管紧张素转换酶抑制剂(ACEI)和血管紧张素受体拮抗剂(ARB)的问世和在临床上广泛应用，是肾脏病治疗领域的一个重大进展。目前ACEI和ARB正在IgA肾病(IgAN)的治疗中发挥越来越重要的作用。     

血管紧张素转换酶抑制剂和 血管紧张素Ⅱ受体拮抗剂在肾脏病的应用

血管紧张素转换酶抑制剂(ACEI)除了降压作用外，对肾脏有特殊的保护作用，现综述如下。     

内皮细胞型一氧化氮合成酶基因表达与血管紧张素转换酶抑制剂

一氧化氮合成酶-Ⅲ单体位于血管内皮细胞,与多数内皮细胞一氧化氮的产生密切相关,而血管紧张素转换酶抑制剂通过上调一氧化氮合成酶基因表达及增加一氧化氮活性而改善内皮功能。本文主要综述血管紧张素转换酶抑制剂与一氧化氮合成酶基因表达的关系。     

Developmental biology of angiotensin-converting enzyme

Molecular, biochemical, and evolutionary studies indicate that somatic angiotensin-converting enzyme (ACE) is developmentally regulated in a tissue-specific manner. However, many important questions remain unanswered. For example, the regulatory mechanisms that control the cell- and stage-specific expression of ACE remain largely unknown. The nature, location, and role of the enzyme involved in the release of plasma membrane-anchored ACE have not been elucidated. Although the expression and localization of ACE are developmentally regulated, the physiological implications of these changes in segmental nephron differentiation remain to be elucidated. Investigations of the cellular and molecular mechanisms mediating the developmental co-regulation of the renin-angiotensin and Kallikrein-kinin system by ACE are a formidable challenge for future research. Received March 18, 1997; accepted June 17, 1997     

血管紧张素转换酶抑制剂对单侧动脉粥样硬化性肾动脉狭窄患者肾功能的影响

目的 观察血管紧张素转换酶抑制剂(ACEI)对单侧动脉粥样硬化性肾动脉狭窄(ARAS)患者肾功能的影响｡方法 结合临床表现及肾动脉造影结果诊断单侧ARAS患者共49例, 分为ACEI组20例与对照组29例｡记录基础血压, 检测Scr､ BUN､ Alb, 以MDRD公式计算估计肾小球滤过率(eGFR),行肾动脉彩超检查测量肾脏阻力指数(RI)｡每月测量血压,每6个月复查Scr､Urea､Alb并计算eGFR, 观察两组患者随访期间肾功能变化｡ 结果 两组患者试验前一般临床资料无显著性差异｡平均随访9.9个月,随访期间两组血压均无明显变化(P > 0.05)｡与试验前比,对照组eGFR无明显变化[(74.5±18.3 )ml·min^-1·(相似文献   

白蛋白对肾小管上皮细胞血管紧张素转换酶表达的影响

目的 观察白蛋白对肾小管上皮细胞血管紧张素转换酶（ACE） mRNA和蛋白水平表达的影响，并探讨尿蛋白激活肾脏局部肾素-血管紧张素系统（RAS）的机制。 方法 分别采用2.5、5、10 g/L的牛血清白蛋白（BSA）刺激人近端肾小管上皮细胞株（HK-2） 6 h和12 h。并分别采用实时定量PCR和Western印迹检测ACE mRNA和蛋白水平的表达。 结果 与对照组相比，随着BSA刺激浓度的增加，HK-2细胞ACE mRNA表达均显著增加（均P <0.05)。同时，Western印迹显示ACE蛋白表达也均显著增加(均P < 0.05)。另外，BSA 10 g/L作用于HK-2细胞6 h和12 h后，ACE mRNA表达显著增加(均P < 0.05)；Western印迹显示ACE蛋白也显著增加（均P < 0.05）。 结论 BSA可显著增加HK-2细胞ACE表达，此作用可能是导致肾间质局部AngⅡ蓄积从而启动肾小管间质纤维化的重要机制之一。     

New perspectives on angiotensin-converting enzyme 2 and its related diseases

Since the worldwide outbreak of coronavirus disease 2019, angiotensin-converting enzyme 2 (ACE2) has received widespread attention as the cell receptor of the severe acute respiratory syndrome coronavirus 2 virus. At the same time, as a key enzyme in the renin-angiotensin-system, ACE2 is considered to be an endogenous negative regulator of vasoconstriction, proliferation, fibrosis, and proinflammation caused by the ACE-angiotensin II-angiotensin type 1 receptor axis. ACE2 is now implicated as being closely connected to diabetes, cardiovascular, kidney, and lung diseases, and so on. This review covers the available information on the host factors regulating ACE2 and discusses its role in a variety of pathophysiological conditions in animal models and humans.     

Comparison of the renal effects of different angiotensin-converting enzyme inhibitors in patients with chronic renal diseases

Background. Angiotensin-converting enzyme inhibitors (ACE-Is) are important agents for preserving renal function in patients with renal diseases. However, the choice of which ACE-I to employ for the treatment of renal disease has not yet been clarified. This study compared the renal effects of enalapril with those of five other ACE-Is in patients with chronic renal diseases. Methods. One hundred and twenty-eight patients with various renal diseases were randomly assigned to six groups according to the ACE-I used: group 1, alacepril (75 mg/day; n = 20); group 2, captopril (37.5 mg/day; n = 19); group 3, cilazapril (1.0 mg/day; n = 23); group 4, delapril (30 mg/day; n = 22); group 5, enalapril (5.0 mg/day; n = 20); and group 6, temocapril (2.0 mg/day; n = 24). Doses of the ACE-I adjusted-converting to the renal function showed similar effects in decreasing blood pressure. Each ACE-I was administered to the patients for 4 months, with monthly examinations. Twenty-four patients dropped out, for various reasons; therefore, results for 104 patients were finally analyzed (group 1, n = 16; group 2, n = 11; group 3, n = 22; group 4, n = 21; group 5, n = 12; group 6, n = 22). Results. There were no differences in absolute or percent changes in mean arterial pressure (MAP), plasma aldosterone (ALDO), the urinary excretion of protein (U-P) and albumin (U-ALB), 24-h creatinine clearance (24-h Ccr), plasma renin activity (PRA), and serum potassium (K) between enalapril and the other ACE-Is, although significant decreases from baseline values in MAP, ALDO, U-P, U-ALB, and 24-h Ccr, and increases in PRA and serum K from baseline values were observed after the administration of enalapril and the other ACE-Is. Conclusions. These results indicated that the renal effects of enalapril were similar to those of the other ACE-Is tested, and suggested, therefore, that any one of the class of ACE-Is could be chosen with the choice being dependent on that considered to lead to best compliance for the patient. The beneficial effects of the class of ACE-Is in patients with renal disease would be expected to be similar. Received: September 6, 2001 / Accepted: November 14, 2001     

Add-on therapy with angiotensin II receptor 1 blocker in children with chronic kidney disease already treated with angiotensin-converting enzyme inhibitors

The standard renoprotection is based on the inhibition of the renin-angiotensin system (RAS) by angiotensin convertase inhibitors (ACEi) or angiotensin II receptor 1 blockers (AT1B). The aim of our study was to analyze the effects of the addition of AT1B to ACEi-based renoprotection in children with chronic kidney disease. We examined 11 children with a mean age of 10.5 years (range, 0.5–18 years) with a mean glomerular filtration rate (GFR) of 61±61 ml/min/1.73 m². In four patients, the primary renal disease was hemolytic uremic syndrome, in three congenital nephrotic syndrome (CNS), in two reflux nephropathy, prune-belly syndrome in one and acute cortical necrosis in one. All patients were treated with complex hypotensive ACEi-based therapy. AT1B losartan was added in a mean dose of 0.9 mg/kg/day. The change in GFR, proteinuria and blood pressure at two 12-month intervals before and after adding AT1B was compared. The results showed that during the 12 months preceding AT1B therapy, there was no change in blood pressure and proteinuria, but the GFR declined in 7 of 11 patients. After the 12th month of add-on therapy with AT1B, there was a significant decrease in both absolute and indexed blood pressure values. Proteinuria decreased in eight patients, did not change in one and increased in two, including one with CNS. The GFR stabilized or increased in eight patients and decreased in three patients with CNS. In 7 of 11 patients, there was a significant, but not threatening increase in serum potassium. In conclusion, add-on renoprotection with AT1B added to ACEi is safe and significantly improves the renoprotective effects of ACEi treatment in children with progressive nephropathies, including patients with advanced CKD.     

Effects of the angiotensin II type 1 receptor antagonist candesartan,compared with angiotensin-converting enzyme inhibitors,on the urinary excretion of albumin and type IV collagen in patients with diabetic nephropathy

Background. We previously reported that the angiotensin II type 1 receptor antagonist candesartan was effective in reducing blood pressure and microalbuminuria in hypertensive patients with diabetic nephropathy after angiotensin-converting enzyme (ACE) inhibitors were replaced due to side effects. In the present study, the clinical effects of candesartan were investigated and compared with ACE inhibitors in patients with stage 2 or 3A diabetic nephropathy, mainly with respect to the effects on the urinary excretion of albumin and type IV collagen. Methods. Forty-nine patients (26 males/23 females) with diabetic nephropathy (stage 2 or 3A), including normotensive patients, were the study subjects. The patients were treated with either an ACE inhibitor (23 patients) or candesartan (26 patients) for 11 ± 3 months. The urinary excretion of albumin and urinary type IV collagen was measured. Results. Posttreatment blood pressure tended to decrease, but such a decrease did not reach a statistically significant level, nor did it show any intergroup difference. The urinary albumin excretion was positively correlated with pretreatment mean blood pressure and left ventricular mass index, but the urinary type IV collagen excretion did not show such correlations. The urinary albumin excretion decreased significantly after treatment to a similar extent in both groups, whereas the urinary type IV collagen excretion decreased significantly only in the candesartan group. Conclusion. It was revealed that ACE inhibitors and candesartan reduced urinary albumin excretion to a similar extent in patients with diabetic nephropathy. From the results of the present study, it is inferred that the renoprotective effect of candesartan in diabetic nephropathy may partially differ from that of ACE inhibitors.     

Prescribing angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in chronic kidney disease

In Australia the number of patients developing end-stage kidney disease is growing. Almost 70% of new cases of treated end-stage kidney disease are due to diabetes, hypertension or glomerulonephritis. The majority of these patients have a chronic decline of renal function over many years before dialysis is required, even when the initial insult is no longer present. Hypertension and the degree of proteinuria are the most important determinants for this progression and ample evidence suggests that angiotensin II is the key player in sustaining both hypertension and proteinuria. Angiotensin II mediates not only haemodynamic changes but also profibrotic and pro-inflammatory processes. Blockade of the renin-angiotensin system decreases proteinuria and slows the progression of both diabetic and non-diabetic proteinuric renal disease. Angiotensin-converting enzyme (ACE) inhibitors are first-line therapy in patients with type 1 diabetes mellitus and nephropathy, whereas angiotensin receptor blockers (ARB) are first-line therapy in patients with type 2 diabetes mellitus and microalbuminuria or overt nephropathy. Finally, treatment with ACE inhibitors delays the progression of proteinuric nephropathy in non-diabetic patients. Combination therapy with ACE inhibitors and ARB may allow a more complete blockade of the renin-angiotensin system and clinical trials show that ACE inhibitor-ARB combinations have an additive antiproteinuric effect of up to 40% compared with ACE inhibitor or ARB alone, without additional blood pressure-lowering effect. Finally, it is important to emphasize that progressive lowering of blood pressure to 120 mmHg is associated with improved renal outcome and that this effect is independent of baseline renal function.