氯沙坦和卡托普利对兔动脉内皮功能和粥样斑块稳定性的影响

目的:研究卡托普利和氯沙坦对高胆固醇饮食兔动脉内皮功能和粥样斑块稳定性的影响,进一步阐明两种药物抗动脉粥样硬化作用机制。方法:31只兔随机分为正常对照组(4只)、高胆固醇组(7只)、氯沙坦组(6只)、卡托普利组(7只)及联合用药组(7只)。用发色底物法测定兔血清一氧化氮(NO)水平,放射免疫分析法测定血浆内皮素(ET)水平;彩色多普勒超声心动图仪测定兔腹主动脉内皮依赖性血管舒张反应(EDVR);流式细胞仪检测动脉壁内皮细胞凋亡;SABC免疫组化染色法检测CD68蛋白表达;RT-PCR方法检测金属基质蛋白酶-1(MMP-1)和组织型MMP-1抑制物(TIMP-1)mRNA表达。结果:与高胆固醇组比较,氯沙坦、卡托普利和联合用药组腹主动脉粥样斑块面积占内膜面积比显著减少,EDVR显著改善,血清ET水平明显下降,NO含量明显升高,斑块内胆固醇含量、CD68蛋白表达和MMP-1 mRNA表达水平显著减低;氯沙坦组内皮细胞凋亡显著减少。结论:氯沙坦和卡托普利可通过改善高胆固醇饮食兔动脉内皮功能和稳定动脉粥样斑块而影响动脉粥样硬化进程。     

卡托普利与缬沙坦对兔动脉粥样硬化肾脏MMP-2及TIMP-2表达的影响

目的研究卡托普利与缬沙坦对兔动脉粥样硬化肾组织中基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)和组织金属蛋白酶抑制因子-2(tissue inhibitor of metalloproteinase-2,TIMP-2)表达的影响。方法30只雄性新西兰大白兔,随机分为4组:高脂饮食组(A组);高脂饮食加卡托普利组(B组);高脂饮食加缬沙坦组(C组);正常对照组(D组)。10周后B超检测造模成功,处死动物。取肾脏标本用免疫组化方法(SABC法)测定MMP-2和TIMP-2的表达。结果与对照组相比,高脂饮食组肾脏MMP-2水平明显降低;高脂饮食加卡托普利组MMP-2水平明显升高,但仍显著低于对照组;高脂饮食加缬沙坦组MMP-2水平明显升高,与对照组无显著差异。高脂饮食组肾脏TIMP-2表达显著高于对照组;高脂饮食加卡托普利组和高脂饮食加缬沙坦组较高脂饮食组TIMP-2明显降低,与对照组无显著差异,两组间也无显著差异。高脂饮食组MMP-2/TIMP-2比值显著低于对照组。结论动脉粥样硬化致兔肾脏局部MMP-2和TIMP-2表达发生的变化,与肾素-血管紧张素系统(renin angiotensin system,RAS)的激活有关,卡托普利和缬沙坦从不同水平阻断RAS后,可减轻MMP-2与TIMP-2表达的变化,达到保护肾脏的作用。     

兔动脉粥样硬化过程中主动脉内膜水含量变化的研究

目的　研究高脂饮食复制兔动脉粥样硬化过程中主动脉内膜水含量的变化。方法　将45只新西兰大白兔随机分为普通饲料组（对照组）、高脂饲料组（高脂组）和高脂饲料加辛伐他汀组（辛伐他汀组）,每组15只。在饲养的第8、16、24周末分别检测对照组、高脂组和辛伐他汀组血清中总胆固醇、甘油三酯和低密度脂蛋白胆固醇的浓度,HE染色观察主动脉的病理形态学变化并测量内膜厚度变化;将高脂组和辛伐他汀组主动脉弓内膜剥离,用真空冷冻干燥方法检测粥样硬化斑块内膜中水含量的变化。结果　①高脂组血清中总胆固醇、甘油三酯和低密度脂蛋白胆固醇浓度均高于对照组和辛伐他汀组（P<0.05）。②对照组主动脉内膜薄而光滑;高脂组动脉内膜明显增厚,光镜下可见大量泡沫细胞和脂质斑块;辛伐他汀组内膜局限性增厚,斑块局限,泡沫细胞数目减少、体积变小。③高脂饮食诱导兔形成动脉粥样硬化过程中,高脂组16周、24周与8周相比粥样硬化斑块内膜中水含量明显减少,24周与16周相比也明显减少（P<0.05）;辛伐他汀组16周、24周斑块内膜中水含量较高脂组相同时间点增多（P<0.05）。结论　兔动脉粥样硬化形成过程中,随时间延长粥样硬化斑块内膜中水含量减少。     

消瘀片消退兔腹主动脉粥样斑块作用的研究

目的 观察消瘀片对兔腹主动脉粥样斑块的消退作用。方法 采用高脂饮食８ｗ加主动脉内膜剥脱术帛成兔腹主动脉粥样硬化模型,通过血管腔内超声技术、光镜和电镜,检查口服消瘀片１６ｗ后兔腹主动脉粥样斑块的消长变化。结果 血管腔内超声检查显示,粥样硬化组管壁呈弥漫性增厚,腔内有环形或半月状粥样斑块低回声区,用消瘀片治疗后,管壁增厚不明显,仅可见散在或短弧形粥样斑块回声区,粥样斑块厚度和斑块面积与粥样硬化组相比明     

益气活血剂对兔胸主动脉粥样硬化形成的作用

目的探讨中药益气活血剂对高脂饮食兔动脉粥样硬化的预防及其作用机制。方法取纯种新西兰大白兔50只,随机分为4组:正常对照组、高脂模型组、益气活血预防组及益气活血治疗组,观察时间为2月。治疗前后检测血脂,治疗结束后分别取主动脉组织作脂质定量,测胸主动脉粥样硬化斑块面积和内膜、血管壁厚度等。结果①益气活血剂治疗可以降低高脂模型组血胆固醇、甘油三酯、低密度脂蛋白胆固醇,其中甘油三酯水平显著降低(P<0.01)。②益气活血剂治疗可减少高脂模型组动脉粥样硬化的形成,使内膜面积、厚度减少(P<0.05),但对管腔面积无明显影响(P>0.05)。③镜下观察发现,高脂模型组主动脉弓内膜充满泡沫细胞,壁上可见明显的粥样斑块;益气活血治疗组动脉壁脂质沉积相对较轻。结论益气活血剂具有降低血脂和抑制动脉粥样硬化形成的作用。     

培哚普利和缬沙坦对兔动脉粥样硬化脑组织核转录因子-κB,诱导型一氧化氮合酶表达的影响

目的建立兔高胆固醇-动脉粥样硬化模型,观察脑组织核转录因子κB(NF-κB)和诱导型一氧化氮合酶(iNOS)的阳性表达,探讨培哚普利、缬沙坦的干预效果及临床意义.方法30只雄性新西兰大白兔,随机分为4组:正常对照组(A组);高脂饮食组(B组);高脂饮食加培哚普利组(C组);高脂饮食加缬沙坦组(D组);喂饲8周后,取脑组织标本用免疫组化方法(SABC法)测定NF-κB的表达;分光光度法测定脑组织iNOS的活力.结果与对照组相比,高脂饮食组脑组织中NF-κB,iNOS水平明显升高(P<0.05);高脂饮食加培哚普利组及高脂饮食加缬沙坦组NF-κB,iNOS水平明显降低(P<0.05),但仍显著高于对照组(P<0.05).结论动脉粥样硬化致脑组织中NF-κB,iNOS表达发生的变化,与肾素-血管紧张素系统(RAS)的激活有关,培哚普利和缬沙坦从不同水平阻断RAS后,可减轻NF-κB,iNOS的表达,达到保护脑组织的作用.     

普罗布考对兔动脉粥样硬化模型C反应蛋白水平的影响及其与斑块稳定性的关系

目的观察兔动脉粥样硬化(AS)模型中C反应蛋白(CRP)的水平与斑块稳定性之间的关系,及普罗布考对CRP水平的影响。方法 20只新西兰大白兔采用随机数字表法分为正常对照组(n=6)、高脂饮食组(n=8)和普罗布考组(n=6)。对照组予普通饲料喂养,高脂饮食组和普罗布考组予高脂饲料喂养。4周后高脂饮食组和普罗布考组行髂动脉内膜球囊损伤术。术后普罗布考组每只大白兔加用普罗布考1g/d口服,10周末取血测血清CRP水平,之后处死动物取损伤处动脉,用HE染色观察动脉病理形态学变化。结果高脂饮食组动脉可见典型的AS斑块形成,普罗布考组无典型斑块形成,内膜增厚较为明显;与高脂饮食组比较,普罗布考组血清CRP水平较低[(8.10±1.02)mg/L比(11.35±2.32)mg/L,P<0.05]。结论 CRP在兔AS模型的表达水平明显增加,与斑块的不稳定性有关,普罗布考有一定的抑制兔AS模型血清CRP表达的作用。     

斑块内血管生成在兔动脉粥样硬化斑块发生发展中的作用

目的观察斑块内血管生成对兔动脉粥样硬化斑块形成与发展的影响。方法用高胆固醇饲料复制动脉粥样硬化兔模型。15只日本大耳白兔随机分为3组:A组,阴性对照组,仅给普通饲料喂养,B、C组给高胆固醇饲料喂养3周,A组及B组肌注白蛋白(2μg/kg)(0d),C组肌注血管内皮生长因子(VEGF1652μg/kg),继续以前饲养方式3周处死动物,截取胸主动脉进行计量组织学及免疫组织化学分析,测定不同组别不同时间点兔血清白细胞介素8(IL8)浓度和血脂浓度。结果(1)斑块面积(A组0,B组1.81%±0.61%,C组24.12%±3.58%)、斑块周径(A组0,B组6.05%±1.62%,C组25.71%±1.97%)及斑块的最大厚度(A组0,B组0.06mm±0.002,C组0.16mm±0.007mm),各组间比较有显著差异(P<0.05)。(2)新生血管的密度(CD34阳性细胞数细胞数/mm2(cells/mm2)A组0,B组12.35±2.02,C组61.15±7.55)各组之间比较有显著差异(P<0.05)。(3)电镜显示:新生血管与动脉粥样斑块相邻,新生血管腔内可见淋巴细胞。(4)血清IL8浓度(+21d时A组[0.05±0.006]pg/ml,B组[0.808±0.308]pg/ml,C组[15.72±4.31]pg/ml)各组间相比有显著差异。(5)此时血清胆固醇浓度B,C两组相比无显著差异。结论斑块内血管生成是动脉粥样斑块的重要病理特征,这个过程可能与炎性反应有关。     

卡托普利和缬沙坦对兔动脉粥样硬化心肌CRP表达的影响

目的探讨卡托普利和缬沙坦从不同水平阻断血管紧张素Ⅱ(AngⅡ)后对心肌C反应蛋白(CRP)表达的影响。方法30只新西兰白兔随机分为四组(:A)高脂饮食组(、B)高脂饮食加卡托普利组(、C)高脂饮食加缬沙坦组(、D)对照组。喂饲10周后,放射免疫法测定血浆AngⅡ含量,取心肌和肝脏用免疫组化方法测定CRP的表达。结果A组心肌CRP表达较D组明显升高(P<0.005)。与A组相比,B组和C组心肌CRP表达显著降低(P<0.05,P<0.025),与D组相比,差异无统计学意义。剔除C组数据后,血浆AngⅡ水平与心肌局部CRP表达存在显著相关性(rs=0.804,P<0.0001)。肝脏CRP表达两两组间差异无统计学意义(P>0.05)。结论AngⅡ与心肌局部组织CRP的表达有显著的相关性;卡托普利和缬沙坦可降低心肌局部CRP的表达,差异无统计学意义。     

兔腹主动脉粥样硬化支架植入后血管壁及内膜改变

目的通过建立兔腹主动脉粥样硬化植入支架动物模型,探讨支架植入后血管壁和内膜变化及发生机制.方法采用兔腹主动脉内膜剥脱术加含1.5%高胆固醇的高脂饮食来建立动脉粥样硬化动物模型,并在此基础上建立兔粥样硬化腹主动脉植入支架模型,并通过组织病理学检查,来揭示支架植入后血管壁和内膜组织形态学变化和病变的发生机制.结果在动脉粥样的动物模型基础上所建立兔腹主动脉粥样硬化植入支架动物模型,经组织形态学和免疫组化检查显示:动物模型目标血管段管腔内膜明显增厚、血管出现不同程度的狭窄,新生内膜中有大量增殖细胞核抗原(PCNA)高表达(着色强度IS:5.268±0.475)的血管平滑肌细胞(VSMC)和泡沫细胞及细胞外基质(ECM).经计算机图像分析仪测定其组织形态学指标分别为残余管腔面积[(9.67±0.18)mm2]、最大内膜厚度[(1.33±0.05)mm]、内膜面积[(5.78±0.23)mm2]和狭窄程度[(31.02±1.91)%].结论本实验成功地建立了兔腹主动脉粥样硬化植入支架动物模型,并认为支架术后血管新生内膜中VSMC过度增殖是导致支架植入后管腔内膜明显增厚的可能原因.     

Additive antiproteinuric effect of combined ACE inhibition and angiotensin II receptor blockade.

BACKGROUND: Limitation of systemic and glomerular hypertension reduces urinary protein excretion and prevents renal function deterioration. OBJECTIVE: To investigate whether, in hypertensive patients with glomerulonephritis, a combination of an angiotensin converting enzyme inhibitor (ACEI, fosinopril 20 mg/day) with an angiotensin receptor blocker (ARB, irbesartan 150 mg/day) produces a more profound antiproteinuric effect than either drug alone. METHODS : Ten non-diabetic patients with glomerulonephritis, normal or slightly reduced but stable renal function (creatinine clearance 40-106 ml/min) without immunosuppression were studied. Clinical evaluations, 24 h blood pressure measurements and laboratory tests were performed as follows: (1) without medication (baseline) and in random sequence; (2) ACEI alone; (3) ARB alone; and (4) combination of ACEI + ARB. Each period lasted for 6 weeks, separated by three washout periods of 4 weeks each without therapy. RESULTS: ACEI and ARB alone reduced proteinuria from 7.9 +/- 7.1 to 5.3 +/- 5.2 and 5.0 +/- 4.9 g/24 h (mean +/- SD), respectively. The combination of ACEI + ARB induced a more remarkable reduction of proteinuria in every patient (to 3.3 +/- 3.7 g/24 h) than either drug alone (P = 0.039 by ANOVA). The enhanced antiproteinuric effect of the combined therapy could not be attributed to a more pronounced reduction of 24 h mean arterial pressure (basal, 106 +/- 8; ACEI, 97 +/- 5; ARB, 98 +/- 5; ACEI+ARB, 95 +/- 5 mmHg) or creatinine clearance (basal, 77 +/- 27; ACEI, 73 +/- 31; ARB 80 +/- 30; ACEI + ARB, 73 +/- 32 ml/min). CONCLUSIONS: A combination of ACEI and ARB in patients with glomerulonephritis produces a more profound decrease in proteinuria than either drug alone. This additive antiproteinuric effect is not dependent on changes in blood pressure or creatinine clearance. A long-term controlled study is required to confirm the positive effect of this treatment on the progression of renal function loss.     

The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT).

OBJECTIVES: We attempted to compare the effect of an angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) on atherosclerotic events. BACKGROUND: Angiotensin-converting enzyme inhibitors and ARBs interrupt the renin-angiotensin system by distinct mechanisms. It is not clear whether ARBs reduce atherosclerotic events such as myocardial infarction (MI) like ACE inhibitors. This evidence gap may reflect the nature of the studies conducted, to date. Placebo-controlled studies enrolled cohorts at low risk of atherosclerotic events (e.g., patients with chronic heart failure, most treated with an ACE inhibitor). One of the main active controlled trials was confounded by a blood pressure difference between treatments. METHODS: We compared the effects of captopril, valsartan, and their combination on atherosclerotic events in 14,703 patients randomized in the Valsartan in Acute Myocardial Infarction Trial (VALIANT). RESULTS: The number of individuals adjudicated as having a fatal or non-fatal MI in the captopril group was 559 (total investigator reported events 798), 587 (796) in the valsartan group, and 554 (756) in the combination group; valsartan versus captopril, p = 0.651 (0.965); combination versus captopril, p = 0.187 (0.350). Overall, all atherosclerotic events examined occurred at a similar frequency in the captopril and valsartan groups. CONCLUSIONS: Angiotensin receptor blockers appear to be as effective as ACE inhibitors in reducing atherosclerotic events, even when used in addition to other secondary preventive treatments. These data, although not conclusive, also support the hypothesis that adding an ARB to an ACE inhibitor may have a small additional anti-infarction effect, a possibility that needs to be prospectively tested.     

Effects of angiotensin-converting enzyme inhibitors or an angiotensin receptor blocker in combination with aspirin and cilostazol on in-stent restenosis

It remains to be determined whether adding an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) to antiplatelet therapy has a therapeutic benefit on in-stent restenosis. After successful coronary stenting, 165 patients (167 lesions) were randomly assigned to a basal (aspirin 162 mg + cilostazol 200 mg/day), ACEI (basal treatment + quinapril 10 mg or perindopril 4 mg/day), or ARB (basal treatment + losartan 50 mg/day) treatment group. Quantitative coronary angiography was performed before, immediately following, and 6 months after stenting. Follow-up coronary angiography was completed in 126 patients (128 lesions). Restenosis rates tended to be higher (12, 26, and 12% for the basal, ACEI, and ARB groups, respectively), and target lesion revascularization rates were higher in the ACEI group than in the other groups (9, 23,* and 5%, respectively, *P < 0.05 versus basal group). Moreover, late lumen loss was higher in the ACEI group than in the basal group (0.60 +/- 0.55, 0.98 +/- 0.61* and 0.73 +/- 0.64 mm in the basal, ACEI, and ARB groups, respectively). The combinations of an ACEI or ARB with aspirin and cilostazol are ineffective for the prevention of in-stent restenosis, and an ACEI may even promote intimal proliferation after stent implantation.     

Antiatherogenic effect of angiotensin converting enzyme inhibitor (benazepril) and angiotensin II receptor antagonist (valsartan) in the cholesterol-fed rabbits

The purpose of this study was to determine whether an angiotensin converting enzyme (ACE) inhibitor, benazepril, and an angiotensin receptor antagonist, valsartan, would decrease atherosclerotic severity in cholesterol-fed rabbits. Male rabbits were fed either: (a) normal rabbit chow; (b) 2% cholesterol diet; (c) 2% cholesterol diet supplemented by benazepril (3 mg/kg per day, subcutaneous injection); or (d) 2% cholesterol diet supplemented by valsartan (1 mg/kg per day, subcutaneous injection). After 12 weeks, the arteries were harvested for histomorphometry and immunohistochemistry. We observed that decreases in serum triglyceride (TG) and total cholesterol (TC) and ACE activity with benazepril-treatment were more than 60, 30, and 84%, respectively, in comparison with the cholesterol group; with valsartan-treatment, TG levels were 53% lower than in the cholesterol group, however, there was no significant difference in TC and ACE activity. The percentage of aortic surface atherosclerotic area, intimal thickness and the ratio of aortic intimal area to medial area were about 40% lower in the benazepril-treated group in comparison with those of the cholesterol group; the difference was more than 60% in the thoracic aorta. The valsartan-treated group had 23% less atherosclerotic area, less effective than benazepril treatment. The percent of PCNA-positive cells and the number of intimal proliferative cells/mm2 were significantly less in the benazepril-treated group compared with the cholesterol group (by 55 and 63%); these parameters were 35 and 17% lower, respectively, with valsartan. The ratio of proliferating macrophages to smooth muscle cells (SMCs) was 3:1 in the cholesterol group, 1:1 in the benazepril and 2:1 in the valsartan-treated group. These results indicate that benazepril could reduce atherosclerotic progression by decreasing macrophage proliferation and accumulation in the arterial wall. The mechanisms for reducing atherosclerotic progression by benazepril and valsartan may be related to reduction of TG and blockade of the angiotensin II action.     

Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 1. A meta-analysis of randomised clinical trials

Most individuals with arterial hypertension or congestive heart failure are insulin-resistant and at a higher risk of developing type 2 diabetes (T2DM). The inhibition of the renin-angiotensin system (RAS), using an angiotensin converting enzyme inhibitor (ACEI) or a selective angiotensin receptor AT1 blocker (ARB), may exert favourable metabolic effects capable of preventing T2DM in high risk individuals. We performed a meta-analysis of randomised clinical trials (RCTs) assessing the effects of RAS inhibition on the incidence of new cases of T2DM in patients with arterial hypertension or congestive heart failure. Ten RCTs with cardiovascular prognosis as primary endpoints analysed the incidence of T2DM as secondary endpoints or as post-hoc analysis after a mean follow-up of 1 to 6 years: five with an ACEI and five with an ARB, compared with a placebo (n = 4) or a reference drug (beta-blocker or diuretic: n = 5; amlodipine: n = 2). Eight RCTs concerned hypertensive patients: STOP Hypertension-2 (lisinopril or enalapril vs beta-blocker or diuretic), CAPPP (captopril vs thiazide or beta-blocker), HOPE (ramipril vs placebo), ALLHAT (lisinopril vs chlorthalidone and lisinopril vs amlodipine), LIFE (losartan vs atenolol), SCOPE (candesartan vs placebo), ALPINE (candesartan vs placebo) and VALUE (valsartan vs amlodipine). Two RCTs concerned patients with congestive heart failure: SOLVD (enalapril vs placebo) and CHARM-overall programme (candesartan vs placebo). Overall, 2 675 new cases of T2DM (7.40%) were observed in the group of 36 167 patients receiving a treatment with ACEI or ARA as compared with 3 842 events (9.63%) in the group of 39 902 control patients. A mean weighed relative risk reduction of new T2DM of 22% (95% CI: 18, 26; p < 0.00001) was observed after RAS inhibition. The beneficial effect was similar with ACEIs and with ARBs as well as in patients with hypertension and in those with heart failure, and was also present whatever the comparator (placebo or beta-blockers/diuretics or amlodipine). The number needed-to-treat to avoid one new case of T2DM averaged 45 patients over 4-5 years. In conclusion, RAS inhibition consistently and significantly reduces the incidence of T2DM in individuals with arterial hypertension or with congestive heart failure. Considering the pandemic of T2DM, such pharmacological approach deserves further attention among the strategies aiming at preventing T2DM.     

缬沙坦和卡托普利对兔血管平滑肌细胞组织因子和组织因子途径抑制物表达及活性的影响

目的观察氧化修饰低密度脂蛋白（ox-LDL）、血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂对血管平滑肌细胞组织因子（TF）和组织因子途径抑制物（TFPI）表达和活性的影响。方法采用组织贴块法培养兔主动脉平滑肌细胞,进行形态学和α-肌动蛋白（actin）免疫组化鉴定。在细胞水平,采用免疫组化、免疫荧光法检测ox-LDL和缬沙坦对TF、TFPI蛋白表达的影响,激光共聚焦法检测ox-LDL和缬沙坦对TF蛋白表达的影响,ELISA法检测ox-LDL、缬沙坦和卡托普利对TF、TFPI抗原表达的影响,发色底物法检测ox-LDL、缬沙坦和卡托普利对TF活性的影响,RT—PCR检测ox-LDL和缬沙坦对TF mRNA表达的影响。结果ox-LDL可增加兔血管平滑肌细胞TF抗原活性和mRNA的表达,在mRNA水平调节TF的表达。ox-LDL可降低兔血管平滑肌细胞TFPI抗原的表达。不同浓度的缬沙坦和卡托普利可明显减少ox-LDL刺激的平滑肌细胞TF抗原表达及活性,缬沙坦对TF表达的影响呈浓度依赖性,同时缬沙坦还可明显减少ox-LDL刺激的TF mRNA表达,证明缬沙坦在mRNA水平上调节TF的表达。不同浓度的缬沙坦和卡托普利可增加ox-LDL刺激的血管平滑肌细胞TFPI抗原的表达,缬沙坦对TFPI表达的影响呈浓度依赖性,该结果由ELISA法得出。结论本实验在细胞水平观察到ox-LDL对血管平滑肌细胞TF表达和活性有促进作用,血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂对其有抑制作用,但这两种药对TFPI的表达有促进作用。从一个新的角度说明这两种药对动脉粥样硬化斑块特别是斑块促凝性的影响,它们可能是通过部分调节TF和TFPI的表达水平而发挥作用的。     

Effectiveness of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker on atrial natriuretic peptide.

The aim of this study was to evaluate the effectiveness of an angiotensin-converting enzyne inhibitor (ACEI, quinapril) or angiotensin II receptor blocker (ARB, candesartan) on atrial natriuretic peptide (ANP) activity in rats with hypertension induced by nitric oxide (NO) inhibition. ACEI and ARB have a number of pharmacologic effects, including blood pressure reduction, myocardial preservation, and an unknown effect in the circulation. The changes in ANP in NO inhibitor-induced hypertensive rats were evaluated in order to elucidate the interaction between ANP and NO in the regulation of blood pressure. Thirty-six rats were divided into 4 groups and administered the experimental agents for 8 weeks: group Control was given regular food (n=9), group N(G)-nitro-L-arginine (L-NNA) was administered L-NNA (25 mg. kg(-1). day(-1), n=9), group ACEI was administered L-NNA and quinapril (10 mg. kg(-1). day(-1), n=9), and group ARB was administered L-NNA and candesartan (10 mg. kg(-1). day(-1), n=9). Blood pressure, plasma ANP, atrial ANP, ANP mRNA, and ANP granules were measured. A significant elevation in blood pressure was observed in group L-NNA. However, there were no increases in plasma ANP (L-NNA: 138.8+/-64.4, Control: 86.7+/-36.4), ANP mRNA (L-NNA: 2.2+/-1.0, Control: 1.7+/-0.5) or ANP granules (L-NNA: 61.1+/-10.2, Control: 64.5+/-8.5). No increase in blood pressure was seen in groups ACEI and ARB. However, plasma ANP (ACEI: 1,392.3+/-1,034.4, ARB: 1,142.8+/-667.3), ANP mRNA (ACEI: 52.8+/-29.1, ARB: 42.9+/-21.2), and ANP granules (ACEI: 122.5+/-23.4, ARB: 136.3+/-33.2) increased significantly. NO inhibitor-induced hypertension caused no changes in ANP concentrations. However, the ACEI and ARB had a direct effect on the induction of ANP secretion. The findings suggest that ANP secretion is directly effected by ACEI and ARB, which seems to play a key role in lowering blood pressure, relieving heart failure symptoms, and preserving the myocardium.     

Impact of angiotensin II receptor blockers on the progression and regression of coronary atherosclerosis: an intravascular ultrasound study.

BACKGROUND: Although angiotensin II receptor blockers (ARB) have been found to reduce the coronary atherosclerotic plaque burden in animal models, it is unknown whether ARB have a similar effect on human coronary arteries. METHODS AND RESULTS: Serial intravascular ultrasound (IVUS) studies of the left main (LM) coronary artery were performed in 64 patients at baseline and after 7-month follow-up. All patients were divided into 2 groups (ARB group: 23 patients; non-ARB group: 41 patients). Three-dimensional volumetric analysis was done throughout the LM coronary artery, and the volume index (VI; volume/length) was calculated for the vessel (VVI), lumen (LVI), and plaque (PVI). No significant difference was found between the 2 groups in baseline clinical characteristics, including age, gender, blood pressure levels, serum cholesterol levels, the presence of diabetes and smoking status. At baseline VVI, LVI and PVI were similar between the groups. In the non-ARB group, VVI, LVI, and PVI did not change between baseline and follow-up. In the ARB group, PVI significantly decreased during follow-up (9.9 +/-3.1 mm2 vs 9.1+/-2.7 mm2, p<0.01), whereas VVI and LVI were unaffected. CONCLUSIONS: This preliminary IVUS study suggests that ARB could cause regression of coronary atherosclerosis in humans.     

缬沙坦、苯那普利及合用时对心肌梗死后心室重构影响的比较

目的　对比血管紧张素转化酶抑制剂 ( ACEI)、选择性 型血管紧张素 受体拮抗剂 ( ARB)以及合用时对心肌梗死 ( MI)后心室重构的影响 ,并初步探讨其作用机制。方法　冠状动脉左前降支结扎后 2 4小时的 SD大鼠被随机分至 B组 (苯那普利 2 m g/ kg/ d)、V组 (缬沙坦 15 mg/ kg/ d)、B+ V组 (苯那普利 1mg/ kg/ d+缬沙坦 7.5 mg/ kg/d)和 C组 (空白对照组 ) ,假手术组 ( S组 )作为正常对照。治疗 6周后测量体重、心脏重量、非梗死心肌胶原含量 ,以及血管紧张素转化酶 ( ACE)、血管紧张素 ( Ang )、醛固酮 ( Ald)的活性或含量。结果　 MI后 6周左心室 ( L V)、右心室 ( RV)重量以及右心室与左心室重量比、心肌胶原含量显著增加 ( C组比 S组 ,P<0 .0 5 ) ,苯那普利、缬沙坦及合用均显著降低以上指标 (与 C组比较 ,均 P<0 .0 5 )。 C组心脏局部 Ang 、ACE和 Ald较 S组明显升高 ( P<0 .0 1) ,三种治疗组均使其显著降低并恢复至正常 (与 C组比较 ,均 P<0 .0 1;与 S组比较 ,均 P>0 .0 5 )。结论　 l.心脏局部肾素 -血管紧张素系统 ( RAS)在左心室重构中发挥重要的作用。2 .ACEI、ARB均有减轻 MI后左心室重构方面的作用。 3 .合用 ACEI与 ARB具有良好的叠加作用     

Comparison of antihypertensive effects of an angiotensin-converting enzyme inhibitor, a calcium antagonist and a diuretic in patients with hypertension not controlled by angiotensin receptor blocker monotherapy

OBJECTIVE: To compare the additional antihypertensive effects of an angiotensin-converting enzyme inhibitor (ACEI), a dihydropyridine calcium antagonist and a diuretic in patients whose hypertension is not controlled by full-dose angiotensin receptor blocker (ARB) monotherapy. DESIGN AND METHODS: Individuals with an ambulatory blood pressure (ABP) that was not controlled by valsartan 160 mg once daily were allocated randomly to two groups: those in group A (n = 35) were assigned randomly to treatment with benazepril 20 mg once daily or chlorthalidone 12.5 mg once daily, whereas patients in group B (n = 29) were assigned randomly to benazepril 20 mg once daily or amlodipine 5 mg once daily. All individuals continued to receive background valsartan 160 mg once daily. After 5 weeks, patients crossed over to the alternative valsartan-based combination treatment of each group for a second 5-week period. Twenty-four-hour ABP monitoring was performed before the random allocation to groups and at the end of each randomized combination pharmacotherapy period. RESULTS: Sixty-four individuals completed the study: 32 men and 32 women (mean +/- SD age 48.2 +/- 7.9 years, average 24-h ABP on valsartan monotherapy 143.4 +/- 12.6/87.7 +/- 7.8 mmHg). Significant additional antihypertensive effects on the average 24-h ABP were obtained with benazepril (8.6 +/- 8.8/6.3 +/- 6.7 mmHg), amlodipine (15.2 +/- 12.9/9.9 +/- 6.8 mmHg) and chlorthalidone (13.5 +/- 11.6/9.5 +/- 7.7 mmHg) (P < 0.001 for all additional antihypertensive effects). The additional effects of amlodipine and chlorthalidone added to valsartan were approximately 6/3.5 mmHg (P < 0.05) greater than that of benazepril. CONCLUSIONS: In patients in whom hypertension was not controlled by full-dose ARB monotherapy, a diuretic, a calcium antagonist or an ACE inhibitor provided significant additional antihypertensive effect. The antihypertensive effects of the ARB-diuretic and the ARB-calcium antagonist combinations were superior to that of the ARB-ACE inhibitor combination.