缬沙坦改善原发性高血压患者血管内皮功能

目的 探讨缬沙坦对原发性高血压患者血管内皮功能的影响.方法 36例原发性高血压患者口服缬沙坦80 mg,1次/d.治疗8周前后,采用高分辨血管外超声法测定治疗前后肱动脉内皮依赖性血管舒张功能;采用硝酸还原法测定血清一氧化氮(NO),化学比色法测定血清超氧化物岐化酶(SOD)及丙二醛(MDA)即脂质过氧化物(LPO)浓度.选择26例正常人作为对照组.结果 治疗前反应性充血引起的肱动脉变化与正常对照组比较明显减弱P＜0.01,治疗后明显改善P＜0.01.服用缬沙坦前与正常对照组的NO水平比较P＜0.01,治疗后与治疗前相比较具有明显的提高P＜0.01.治疗前与对照组相比SOD活性较对照组明显降低(P＜0.01),MDA活性明显增高(P＜0.01),经缬沙坦治疗后SOD活性较治疗前明显增高(P＜0.01),MDA活性明显降低(P＜0.01).单因素相关分析显示:原发性高血压患者在进行缬沙坦治疗后反应性充血时肱动脉内径的变化与NO水平呈线性正相关P＜0.01,r=0.798.结论 缬沙坦可改善血管内皮依赖性舒张功能,减少氧化应激.     

缬沙坦改善原发性高血压患者血管内皮功能

目的探讨缬沙坦对原发性高血压患者血管内皮功能的影响。方法36例原发性高血压患者口服缬沙坦80mg,1次/d。治疗8周前后,采用高分辨血管外超声法测定治疗前后肱动脉内皮依赖性血管舒张功能;采用硝酸还原法测定血清一氧化氮(NO),化学比色法测定血清超氧化物岐化酶(SOD)及丙二醛(MDA)即脂质过氧化物(LPO)浓度。选择26例正常人作为对照组。结果治疗前反应性充血引起的肱动脉变化与正常对照组比较明显减弱P<0.01,治疗后明显改善P<0.01。服用缬沙坦前与正常对照组的NO水平比较P<0.01,治疗后与治疗前相比较具有明显的提高P<0.01。治疗前与对照组相比SOD活性较对照组明显降低(P<0.01),MDA活性明显增高(P<0.01),经缬沙坦治疗后SOD活性较治疗前明显增高(P<0.01),MDA活性明显降低(P<0.01)。单因素相关分析显示:原发性高血压患者在进行缬沙坦治疗后反应性充血时肱动脉内径的变化与NO水平呈线性正相关P<0.01,r=0.798。结论缬沙坦可改善血管内皮依赖性舒张功能,减少氧化应激。     

缬沙坦改善高血压房颤患者血管内皮功能

目的 比较缬沙坦和氨氯地平对老年高血压伴永久性心房颤动(房颤)患者内皮功能及炎症因子的影响.方法 将年龄60岁以上的老年原发性轻中度(1～2级)高血压伴永久性房颤的患者64例,随机分为缬沙坦组(80～160 mg/d)32例和氨氯地平组(5～10 mg/d)32例,分别接受12周的缬沙坦和氨氯地平治疗.治疗期间监测血压,分别于治疗前和治疗12周后测定血浆血管假性血友病因子(vWF)、一氧化氮(NO)、高敏C反应蛋白(hsCRP)水平,同时选择年龄匹配的高血压窦性心律者20例作为对照组,并检测上述指标.结果 两组患者治疗后血压均明显下降(P＜0.01),且下降程度差异元显著性;治疗前,两组房颤患者NO水平显著低于对照组(P＜0.01),vWF、hsCRP水平显著高于对照组(P＜0.01),但两组房颤患者之间上述3项指标元明显差别;降压治疗后,和治疗前相比,两组房颤患者NO水平显著升高(P＜0.01),vWF、hsCRP水平显著降低(P＜0.01);在相同降压程度条件下,和氨氯地平组相比,缬沙坦组降低vWF、hsCRP水平和升高NO水平更显著(P＜0.05).结论 缬沙坦和氨氯地平均能有效降压,改善内皮功能及降低炎症因子;在同等降压条件下,缬沙坦改善内皮功能和降低炎症因子的作用强于氨氯地平.这可能对预防高血压房颤患者脑卒中的发生有一定的意义.     

缬沙坦改善高血压房颤患者血管内皮功能

目的比较缬沙坦和氨氯地平对老年高血压伴永久性心房颤动(房颤)患者内皮功能及炎症因子的影响。方法将年龄60岁以上的老年原发性轻中度(1~2级)高血压伴永久性房颤的患者64例,随机分为缬沙坦组(80~160mg/d)32例和氨氯地平组(5~10mg/d)32例,分别接受12周的缬沙坦和氨氯地平治疗。治疗期间监测血压,分别于治疗前和治疗12周后测定血浆血管假性血友病因子(vWF)、一氧化氮(NO)、高敏C反应蛋白(hsCRP)水平,同时选择年龄匹配的高血压窦性心律者20例作为对照组,并检测上述指标。结果两组患者治疗后血压均明显下降(P<0·01),且下降程度差异无显著性;治疗前,两组房颤患者NO水平显著低于对照组(P<0·01),vWF、hsCRP水平显著高于对照组(P<0·01),但两组房颤患者之间上述3项指标无明显差别;降压治疗后,和治疗前相比,两组房颤患者NO水平显著升高(P<0·01),vWF、hsCRP水平显著降低(P<0·01);在相同降压程度条件下,和氨氯地平组相比,缬沙坦组降低vWF、hsCRP水平和升高NO水平更显著(P<0·05)。结论缬沙坦和氨氯地平均能有效降压,改善内皮功能及降低炎症因子;在同等降压条件下,缬沙坦改善内皮功能和降低炎症因子的作用强于氨氯地平。这可能对预防高血压房颤患者脑卒中的发生有一定的意义。     

阿托伐他汀改善高血压合并高血脂患者的血管内皮功能

目的 探讨阿托伐他汀对高血压合并高血脂患者血管内皮功能的影响.方法 共入选172例高血压合并高血脂患者,随机分为阿托伐他汀10 mg组(n=92)和20 mg组(n=80),阿托伐他汀睡前服用,1次/d,治疗12周.另选取56例正常体检者为对照组.检测治疗前后3组研究对象血压、血脂、一氧化氮(NO)、内皮素(ET)和降钙素基因相关肽(CGRP)的变化.结果 治疗前阿托伐他汀组的血压和血脂明显高于对照组,治疗后血压和血脂显著下降(P<0 01),与阿托伐他汀10 mg组比较,20 mg组能更进一步改善高血压患者的血脂异常.阿托伐他汀组治疗前的ET明显高于对照组,NO和CGRP均明显低于对照组,阿托伐他汀治疗后ET显著下降,NO和CGRP显著升高(P<0 01),与阿托伐他汀10 mg组比较,20 mg组能更进一步改善高血压患者的血管内皮功能.结论 阿托伐他汀可改善高血压合并高血脂患者的血管内皮功能,并有剂量依赖性.     

阿托伐他汀改善高血压合并高血脂患者的血管内皮功能

目的探讨阿托伐他汀对高血压合并高血脂患者血管内皮功能的影响。方法共入选172例高血压合并高血脂患者,随机分为阿托伐他汀10 mg 组(n=92)和20 mg 组(n=80),阿托伐他汀睡前服用,1次/d,治疗12周。另选取56例正常体检者为对照组。检测治疗前后3组研究对象血压、血脂、一氧化氮(NO)、内皮素(ET)和降钙素基因相关肽(CGRP)的变化。结果治疗前阿托伐他汀组的血压和血脂明显高于对照组,治疗后血压和血脂显著下降(P<0.01),与阿托伐他汀10 mg 组比较,20 mg 组能更进一步改善高血压患者的血脂异常。阿托伐他汀组治疗前的 ET 明显高于对照组,NO 和 CGRP 均明显低于对照组,阿托伐他汀治疗后 ET 显著下降,NO 和 CGRP显著升高(P<0.01),与阿托伐他汀10 mg 组比较,20 mg 组能更进一步改善高血压患者的血管内皮功能。结论阿托伐他汀可改善高血压合并高血脂患者的血管内皮功能,并有剂量依赖性。     

高血压前期患者血管内皮功能的变化

目的探讨高血压前期患者血管内皮功能的变化。方法选择高血压前期患者76例（A组）、正常血压者80例（B组）和原发性高血压患者80例（C组）,采用酶联免疫吸附双抗体夹心法检测受试对象的血浆血管性假血友病因子（VWF）和单核细胞趋化蛋白1（MCP-1）水平。采用高分辨率血管超声法检测患者肱动脉血流介导的血管舒张功能。结果 A、C组VWF、MCP-1水平高于B组（P〈0.05）。A、C组反应性充血后肱动脉内径变化率低于B组（P〈0.05）;含服硝酸甘油后肱动脉内径变化率各组间比较无统计学差异（P〉0.05）。结论高血压前期患者已经存在血管内皮功能障碍。     

缬沙坦对高血压患者血管内皮功能的影响

目的探讨高血压患者血管内皮功能的变化及缬沙坦对其影响。方法52例原发性高血压患者缬沙坦治疗8周与22例正常血压者对照,检测缬沙坦治疗前后血浆内皮素-1(ET-1)浓度,以及肱动脉超声检测血管内皮舒张功能的变化。结果(1)高血压组血浆ET-1明显高于对照组(P<0.01),缬沙坦治疗后明显下降(P<0.01)。(2)高血压组血流介导的肱动脉舒张低于对照组(P<0.01),缬沙坦治疗后明显改善(P<0.01)。结论高血压患者血管内皮功能受损,缬沙坦在降低血压的同时能改善血管内皮功能。     

替米沙坦改善代谢综合征患者血管内皮功能

目的观察替米沙坦对代谢综合征患者血管内皮功能的影响。方法 76例代谢综合征患者随机分为常规组和替米沙坦组,每组38例,同时选择健康体检者38例作为对照组。替米沙坦组在常规用药的基础上加服替米沙坦80 mg/d,治疗3个月。检测三组患者治疗前后血糖、血脂代谢指标、血浆一氧化氮含量及炎症因子肿瘤坏死因子α、白细胞介素6和C反应蛋白水平,观察血压及血管内皮舒张功能变化。结果治疗后常规组和替米沙坦组的血压、空腹血糖均明显下降(P<0.01),但两组间的血压、空腹血糖相比差异无统计学意义(P>0.05)。治疗后替米沙坦组的肱动脉血流介导的舒张内径(FMD)(P<0.05)、一氧化氮含量明显升高(P<0.01),肿瘤坏死因子α、白细胞介素6和C反应蛋白水平降低(P<0.05),且与常规组相比差异有统计学意义(P<0.05);而常规组FMD、一氧化氮含量及炎症因子水平与治疗前比无明显变化(P>0.05)。结论替米沙坦可降低代谢综合征患者血浆炎症因子水平,抑制炎症反应,升高一氧化氮含量,改善血管内皮功能。     

Experimental approach to improve endothelial barrier function in myocardium

Recently, we showed that activated factor XIII (FXIIIa) has a direct influence on permeability (P) of cultured endothelial monolayer. Clinical investigation on children operated on for congenital heart disease has demonstrated a distinct correlation between decrease of endothelial barrier function (edema formation) and reduced FXIII activity. Our experiments investigated whether significant effects of FXIII could also be shown in a full-organ model. The effect of FXIII on endothelial barrier function was studied by determining the passage of trypan blue-labeled albumin in a model of cultured monolayers of porcine aortic endothelial cells and changes in myocardial water content of saline-perfused rat hearts in a Langendorff-circuit. The plasma FXIIIa (1 U/ml) reduced albumin permeability of aortic endothelial monolayers within 20 minutes from a basal value of 5.9±0.4×10^–6 cm/second by 30±7% whereas the nonactivated plasma FXIII had no effect on permeability. Reduction of permeability to the same extent (by 34±9%) could also be obtained with a thrombin-activated recombinant factor XIII A subunit (rhu FXIII; 1 U/ml) in this culture model. The effect of factor XIII A* on permeability was dose dependent with maximum effect at 5 U/ml (52±11% reduction of permeability compared with control), and existed even if cells had hyperpermeability stress (KCN/2-DG). Activated rhuFXIII prevented the increase in myocardial water content in anoxic-reperfused rat hearts (448±24 vs 517±29 ml/100g dry weight). The data of the present study show that FXIII has a stabilizing effect at the site of endothelial cells not only in cultured monolayers but also in a model of the anoxic perfused rat heart.Presented in part at the 40th Annual World Congress, International College of Angiology, Lisbon, Portugal, June 1998.     

Periodontal care may improve endothelial function

BackgroundPeriodontitis is a chronic, infectious, insidious disease of the tooth-supporting structures that causes a general inflammatory response. The aims of this study were to determine whether periodontitis is associated with endothelial dysfunction leading to cardiovascular events and whether proper management of periodontal disease would improve endothelial function and prevent cardiovascular events in the future.MethodsTwenty-two patients (12 women, 10 men; 40 ± 5 years old) took part in the study. All had severe periodontitis (without systemic disorders) and were all treated conservatively. Thirteen patients returned for a second visit after 3 months of treatment. Endothelial function and periodontal status were evaluated on entry into the study and 3 months following treatment. Ten age-matched, healthy volunteers without periodontal disease served as the control group.ResultsThere was a significant difference between the patient group and the healthy controls: FMD% 4.12 ± 3.96 vs. 16.60 ± 7.86% (p = 0.0000). Periodontitis improved significantly in all 13 patients who completed 3 months of treatment, and their endothelial function improved as well: FMD% 4.12 ± 3.96% vs. 11.12 ± 7.22% (p = 0.007). No difference was found in FID% before and after 3 months of treatment: 20.97 ± 10.66% vs.17.94 ± 6.23% (p = NS).ConclusionsPeriodontitis may be an insidious cause of endothelial dysfunction and cardiovascular events. Treating periodontitis can improve endothelial function and be an important preventive tool for cardiovascular disease.     

HSF1 and constitutively active HSF1 improve vascular endothelial function (heat shock proteins improve vascular endothelial function)

We have been examining the role of heat shock factor 1 (HSF1) in the pleiotropic effects of statins. In parallel studies, we found that statin induces the nuclear translocation of HSF1 and that a decoy oligonucleotide encoding the heat shock element inhibits the statin-induced expression of heat shock protein 70, endothelial nitric oxide synthase (eNOS) and thrombomodulin. Also, in vascular endothelial cells, increases in the expression of human HSF1 corresponded with elevated steady-state levels of eNOS and thrombomodulin and reduced levels of endothelin-1 and plasminogen activator inhibitor-1. We also found that heat shock proteins induced eNOS and thrombomodulin expression and reduced PAI-1 and ET-1 expression. In particular, a combination of HSP70 and HSP90 strongly induced eNOS expression and reduced PAI-1 expression. In the current studies, we generated a constitutively active form of HSF1 and found that it is more effective than the wild-type HSF at inducing thrombomodulin and eNOS expression and decreasing endothelin-1 and plasminogen activator inhibitor-1 expression. These results show that the wild-type and constitutively active forms of HSF1 induce anticoagulation and relaxation factors in vascular endothelial cells and could therefore be used to treat cardiovascular disease.     

Oral contraceptives improve endothelial function in amenorrheic athletes

Athletic amenorrhea has been associated with endothelial dysfunction and unfavorable lipid profile. Estrogen substitution may reverse these metabolic consequences. The aim of this study was to evaluate the effects of oral contraceptives (OCs) on endothelial function measured as flow-mediated dilatation (FMD) of the brachial artery, the lipid profile, and blood markers of endothelial activation (inflammation) in amenorrheic athletes. Age- and body mass index-matched groups of young endurance athletes with amenorrhea (n = 11), regularly cycling athletes (n = 13), and sedentary controls (n = 12) were examined before and after 9 months of treatment with a low dose, monophasic, combined OC (30 mug ethinyl estradiol and 150 mug levonorgestrel). The amenorrheic athletes displayed the lowest FMD at baseline and the largest increase after OC treatment. FMD also increased in the control group, but not in the regularly menstruating athletes, who had the highest values of FMD before treatment. All three groups, particularly the controls, showed moderate unfavorable changes in the lipid profile in accordance with previous known effects of a second generation OC. Furthermore, there was an overall increase in some inflammatory markers (high sensitive C-reactive protein and TNF-alpha) and a decrease in one of the markers (vascular cell adhesion molecule-1). We conclude that amenorrheic athletes benefit from treatment with OC with respect to endothelial function. OC treatment is also associated with some modest alterations in the lipid profile and in markers of inflammation.     

门静脉高压药物治疗的新进展

肝硬化门脉高压形成的机制主要是肝内阻力增加和门脉血流量增多.肝内阻力增加是始动因素,其原因主要分机械性和动力性因素:机械性因素是不可逆的,而动力性因素是可逆的.近年来发现许多血管活性物质可以解除或是减弱这种可逆性的梗阻.而且目前的外科分流术和经颈静脉肝内门体分流术可能引起许多并发症如肝性脑病、支架再梗阻等.于是,人们对门脉高压的药物治疗进行了大量的实验研究并有了许多新的认识.本文将主要阐述门脉高压的药物治疗的新进展.     

Mediterranean and low-fat diets improve endothelial function in hypercholesterolemic men.

BACKGROUND: The regulatory function of the endothelium is altered in hypercholesterolemia, and the subsequent endothelial dysfunction plays a central role in the development of atherosclerosis. OBJECTIVE: To determine whether endothelial function in hypercholesterolemic patients is affected by replacing a saturated fat-enriched diet with a low-fat, low-saturated fat diet (the U.S. National Cholesterol Education Program stage 1 [NCEP-1] diet) or a diet rich in monounsaturated fat (such as that common in Mediterranean countries). DESIGN: Intervention dietary study with a baseline phase and two randomized crossover dietary periods. SETTING: Hospital Universitario Reina Sofía, Córdoba, Spain. PATIENTS: 22 hypercholesterolemic men. INTERVENTION: Patients followed a diet high in saturated fat, then were assigned in a crossover design to the NCEP-1 diet or a Mediterranean diet. Each dietary period lasted 28 days. MEASUREMENTS: Plasma P-selectin levels, lipid concentrations, and endothelial function. RESULTS: Compared with the saturated fat diet, flow-mediated dilatation increased during the Mediterranean diet but not during the NCEP-1 diet. In addition, levels of plasma cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and P-selectin decreased during the NCEP-1 and Mediterranean diets. CONCLUSION: In hypercholesterolemic men, diets low in fat (especially saturated fat) and diets rich in monounsaturated fats improve endothelial function.     

Effect of the renin--angiotensin system on the vessel wall: using ACE inhibition to improve endothelial function

Plasma renin activity and cardiovascular disease (CVD) incidence correlate closely in people with hypertension. The effects of angiotensin II (Ang II) on blood pressure (BP) are important in hypertensive patients; accumulating data suggest that the growth effects of Ang II in the cardiovascular system play a critical role in the development of atherosclerosis. Atherosclerosis development in hypertensive patients requires fundamental changes in endothelial structure and function. Key among the factors that may affect the endothelium is the renin--angiotensin--bradykinin system. Ang II, independent of other environmental and neurohormonal factors, mediates the vessel wall changes critical for the development of atherosclerotic disease. A strong correlation appears to exist between Ang II and CVD. Blockade of the renin-angiotensin system has a major impact on arterial structure and function independent of BP. Certain angiotensin-converting enzyme (ACE) inhibitors produce significant improvements in arterial compliance, which may yield a reduction in cardiovascular events. Blockade of the neurohormonal system may be a critical first-line approach to management of hypertension in an effort to prevent or reverse endothelial dysfunction. Moreover, the effects of ACE inhibition, in addition to its effect on BP, suggest that this therapeutic approach may be appropriate for managing patients at risk of CVD who do not yet have hypertension. The ideal antihypertensive agent should yield smooth, consistent BP control over the entire 24-hour period, both to avoid BP variability that places patients at increased risk of cardiovascular events and to offer protection during the vulnerable early morning hours when patients are well known to be at high risk.     

Wine polyphenols improve endothelial function in large vessels of female spontaneously hypertensive rats

Red wine polyphenols (RWPs) have been reported to prevent hypertension and endothelial dysfunction. Several individual RWPs exert estrogenic effects. We analyzed the possible in vivo protective effects on blood pressure and endothelial function of RWPs in female spontaneously hypertensive rats (SHR) and its relationship with ovarian function. RWPs (40 mg/kg by gavage) were orally administered for 5 weeks. Ovariectomized rats showed both increased isoprostaglandin F(2alpha) excretion and aortic superoxide production and reduced relaxant response to acetylcholine and contraction to the endothelial nitric oxide synthase (eNOS) inhibitor l-NAME measured in the aorta but similar blood pressure, as compared with sham-operated rats. Moreover, in ovariectomized rats aortic eNOS expression was unchanged, whereas caveolin-1, angiotensin II receptor (AT)-1, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22(phox) and p47(phox) expression was increased compared with sham-operated rats. In both ovariectomized and sham-operated SHR, RWPs reduced systolic blood pressure, urinary isoprostaglandin F(2alpha) excretion, and aortic O(2)(-) production, improving the endothelium-dependent relaxant response to acetylcholine in SHR. These changes were associated with unchanged aortic eNOS expression, whereas caveolin-1 was increased and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22(phox) and p47(phox) expression was reduced. RWPs had no effect on the AT-1 overexpression found in ovariectomized animals. All these results suggest that a chronic treatment with RWPs reduces hypertension and vascular dysfunction through reduction in vascular oxidative stress in female SHR in a manner independent of the ovarian function.     

血管内皮细胞功能损伤机制的研究进展

血管内皮细胞(VEC)作为血管腔内的一层特化细胞,是血液和组织之间的关键调控界面,因此也成为了多种血管损伤因素的潜在靶点。VEC损伤是多种慢性疾病的共同生理变化,也是包括动脉硬化在内的多种心血管疾病的初始发病机制,其具体机制尚有待进一步阐明。探究VEC损伤的普遍病理机制有助于改善心血管疾病的发展和预后。文章主要就血管活性物质、炎症反应、氧化应激、凝血系统及其他因素等引起VEC损伤的普遍损伤机制进行综述。