Carvedilol improves endothelium-dependent dilatation in patients with coronary artery disease

OBJECTIVE: Flow-mediated, endothelium-dependent dilatation (FMD) of the coronary and peripheral circulation is impaired by increased oxidative stress in patients with coronary artery disease (CAD). Carvedilol is a novel beta-blocker that also shows an antioxidant effect in vitro. However, the effect of carvedilol on endothelial dysfunction associated with established coronary atherosclerosis has not been examined in the clinical setting. METHODS: We studied 29 patients with CAD, including 17 with recent myocardial infarction and 12 with stable effort angina pectoris. Nineteen patients received carvedilol (10 with infarction and 9 with angina), and 10 were treated with placebo (7 with infarction and 3 with angina). We also studied 13 age- and sex-matched control subjects. Brachial FMD during reactive hyperemia and nitroglycerin-induced, endothelium-independent dilatation were assessed by high-resolution ultrasound. RESULTS: FMD was smaller in patients with CAD compared with controls, although nitroglycerin-induced dilatation was similar. Carvedilol significantly improved FMD after long-term treatment (5. 1% +/- 0.4% at baseline to 7.8% +/- 0.3% after 4 months; P <.01) but not after short-term treatment (5.1% +/- 0.4% at baseline to 5.0% +/- 0.7% after 2 hours). Placebo therapy had no effect on endothelial dysfunction. Neither carvedilol nor placebo had an effect on nitroglycerin-induced dilatation after short- and long-term treatment. Long-term carvedilol therapy also significantly decreased the plasma level of thiobarbituric acid-reactive substances compared with placebo (carvedilol, 5.8 +/- 0.4 nmol/mL to 4.6 +/- 0.3 nmol/mL, P <.01; placebo, 5.9 +/- 0.4 nmol/mL to 5.8 +/- 0.4 nmol/mL, P = not significant). CONCLUSION: These findings suggest that the improvement of endothelial function by carvedilol may be caused by its antioxidant activity.     

冠心病患者血管内皮功能障碍与动脉弹性关系的研究

目的　探讨冠心病患者血管内皮功能障碍与动脉弹性的关系。方法　采用高分辨率血管超声法检测 30例冠心病患者与 30例正常对照组肱动脉血流介导的内皮依赖性血管舒张功能(FMD);应用动脉弹性功能检测仪测定受试者的大动脉弹性指数 (C1 )和小动脉弹性指数 (C2 )。结果　冠心病组血流介导的肱动脉舒张反应明显低于对照组[ (5 17±2 13)% 与 (11 10±4 36)%,P<0 05];冠心病组与正常对照组的C1 差异无统计学意义 [ ( 11 59±4 56 )ml/mmHg( 1mmHg=0 133kPa) ×10与 (12 11±3 82)ml/mmHg×10, P>0 05],但冠心病组的C2 明显低于正常对照组[ (4 20±1 80)ml/mmHg×100与 (6 26±2 36)ml/mmHg×100, P<0 05],冠心病组血流介导的肱动脉舒张反应与C2 呈正相关(r=0 53, P<0 05)。结论　冠心病患者肱动脉内皮依赖血管舒张功能受损和C2 降低,且两者之间呈正相关,提示C2 可作为一种评价血管内皮功能的新指标。     

普伐他汀对Ⅱ型糖尿病并发冠心病患者肱动脉内皮舒张功能的影响

目的:探讨普伐他汀对Ⅱ型糖尿病并发冠心病患者肱动脉内皮舒张功能的影响。方法:45例Ⅱ型糖尿病并发冠心病患者随机分为常规治疗组和普伐他汀治疗组,治疗4周前后均抽静脉血测定血脂,采用高分辨超声法检测治疗前后肱动脉内皮依赖性舒张功能（FMD）和非内皮依赖性舒张功能（NMD）。结果:普伐他汀治疗4周后肱动脉FMD（6.32±0.35）%较治疗前（2.50±0.21）%显著改善（P<0.05）,而肱动脉NMD无显著性差异（P>0.05）。结论:短期口服普伐他汀（40 mg/d）对Ⅱ型糖尿病并发冠心病患者受损的血管内皮功能有改善作用。     

老年女性冠心病患者颈动脉粥样硬化和血管内皮依赖性舒张功能的探讨

目的　观察老年女性冠心病患者颈动脉内中膜厚度 (IMT)、粥样斑块发生率及肱动脉内皮依赖性舒张功能的情况。方法　用高分辨超声技术对 89例老年女性行肱动脉血流介导的舒张功能 (FMD)、IMT及颈动脉粥样斑块的检测。结果　老年女性冠心病组FMD较对照组明显减弱 ,分别为 (3.5± 3.1) %及 (7.6± 3.5 ) % ,P <0 .0 0 1,老年女性冠心病组及对照组IMT分别为 (0 .88± 0 .2 0 )mm及 (0 .6 5± 0 .2 3)mm ,颈动脉粥样斑块发生率分别为 6 2 .2 %及11.4 % ,两组比较差异具有显著性意义 ,P <0 .0 0 1。结论　老年女性冠心病患者存在着严重的血管内皮依赖性舒张功能障碍以及颈动脉粥样硬化 ,颈动脉B超及肱动脉血流介导的舒张功能对老年女性冠心病患者有一定的预测价值。     

Long-term treatment with eicosapentaenoic acid improves exercise-induced vasodilation in patients with coronary artery disease.

We have previously shown that long-term treatment with eicosapentaenoic acid (EPA) improves endothelium-dependent vasodilation of the atherosclerotic arteries in both animals and humans. The aim of the present study was to examine whether EPA treatment also improves metabolic vasodilation evoked by exercise in patients with coronary artery disease (CAD). Forearm blood flow (FBF) was measured by strain gauge plethysmography in 10 patients with stable CAD, before and 3 months after oral treatment with EPA (1,800 mg/kg). FBF was measured at rest and during intra-arterial infusion of acetylcholine or sodium nitroprusside, before and after intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA, an inhibitor of nitric oxide (NO) synthesis). A rhythmic handgrip exercise was also performed for 3 min before and after L-NMMA, and FBF was measured for 3 min just after the handgrip exercise. These protocols were repeated after the long-term treatment with EPA for 3 months. The long-term treatment with EPA significantly improved the FBF responses to acetylcholine (p < 0.01), which was significantly reduced by acute administration of L-NMMA (p < 0.01). By contrast, the EPA treatment did not affect the endothelium-independent responses to sodium nitroprusside. Metabolic increases in FBF caused by the handgrip exercise were not significantly decreased by L-NMMA before the EPA treatment. The EPA treatment significantly augmented the exercise-induced increases in FBF (p < 0.05) and L-NMMA acutely abolished this augmentation (p < 0.01). These results indicate that long-term treatment with EPA improves both endothelium-dependent and exercise-induced forearm vasodilations in patients with CAD and that NO is substantially involved in the EPA-induced improvement of the FBF responses in patients with CAD.     

Vitamin E administration improves impairment of endothelium-dependent vasodilation in patients with coronary spastic angina

Objectives. We examined the effects of oral administration of vitamin E, an antioxidant, on endothelium-dependent vasodilation in patients with coronary spastic angina.Background. We have recently reported that endothelium-dependent vasodilation is impaired in patients with coronary spastic angina (CSA). Furthermore, it is known that oxidative stress may play an important role in the impairment of endothelium-dependent vasodilation in cardiovascular diseases.Methods. With the ultrasound technique, flow-dependent vasodilation of the brachial arteries during reactive hyperemia was examined before and after treatment for a month with either oral administration of vitamin E (α-tocopherol acetate, 300 mg/day) or placebo, which is randomly assigned, in patients with CSA (n = 60).Results. Before treatment, patients with CSA had impaired flow-dependent vasodilation, lower plasma levels of α-tocopherol and higher plasma levels of thiobarbituric acid reactive substances (TBARS), as compared with age- and sex-matched control subjects (n = 60) (flow-dependent vasodilation: 3.1 ± 1.8 vs. 7.1 ± 2.5%, p < 0.001; α-tocopherol levels: 8.9 ± 1.8 vs. 10.8 ± 1.8 μg/ml, p < 0.001). In patients with CSA, treatment with vitamin E restored flow-dependent vasodilation (3.1 ± 1.7 vs. 8.3 ± 2.0%, p < 0.001), and this improvement was associated with the decreases in plasma TBARS levels and anginal attacks.Conclusions. The results indicate that vitamin E treatment improved endothelium-dependent vasodilation and decreased plasma TBARS levels in patients with CSA. Thus, increased oxidative stress may contribute to endothelial dysfunction and anginal attacks in patients with CSA.     

冠心病患者血管内皮功能障碍及动脉弹性与冠状动脉Gensini评分的关系

目的:探讨冠心病患者血管内皮功能障碍及动脉弹性与冠状动脉造影Gensini评分的关系.方法:采用高分辨率血管超声法检测冠心病患者(76例)与正常对照组(30例)肱动脉血流介导的内皮依赖性血管舒张功能(FMD);应用动脉弹性功能检测仪测定受试者的大动脉弹性指数(C1)和小动脉弹性指数(C2);对冠心病患者进行冠状动脉造影,并通过Gensini评分系统对冠心病患者冠状动脉病变进行评分.结果:冠心病组血流介导的FMD明显低于对照组[(6.94±4.21)%∶(11.10±4.36)%,P<0.05];冠心病组与对照组的C1差异无统计学意义[(117.0±38.1)∶(121.1±38.2)ml/mmHg(1 mmHg=0.133 kPa),P>0.05],但冠心病组的C2明显低于对照组[(516.0±2640)∶(626.0±236.0)ml/mmHg,P<0.05],冠心病患者FMD及C2均与冠状动脉造影Gensini评分呈负相关(r=-0.380,P<0.01及r=-0 329,P<0.01).结论:C2和FMD似可作为评价冠状动脉病变程度的新指标.     

Captopril improves impaired endothelium-dependent vasodilation in hypertensive patients.

Animal studies suggest that some angiotensin converting enzyme inhibitors augment endothelium-dependent vasorelaxation. We aimed to determine if captopril augments endothelium-dependent vasodilation in middle-aged hypertensive patients. By using strain-gauge plethysmography, forearm vasodilation evoked with intra-arterial acetylcholine (4, 8, 16, and 24 micrograms/min) or nitroprusside (0.2, 0.4, 0.8, and 1.2 micrograms/min) was examined before and after captopril administration (25 mg per os). Before captopril, forearm vasodilation with acetylcholine was less in hypertensive patients (n = 12) than in age-matched (n = 7) or young (n = 7) normotensive subjects, but forearm vasodilation with nitroprusside did not differ among the three groups. Captopril improved forearm vasodilation in hypertensive patients (n = 7) with acetylcholine but nitroprusside did not. In contrast, nifedipine (10 mg per os) did not alter forearm vasodilation with acetylcholine or nitroprusside in hypertensive patients (n = 5). The decreases in mean blood pressure caused by captopril and nifedipine in hypertensive subjects were comparable. Captopril did not alter forearm vasodilation with acetylcholine or nitroprusside in young normotensive subjects (n = 7). These results suggest that captopril in hypertensive patients may acutely improve impaired endothelium-dependent forearm vasodilation that does not result from reduction in blood pressure per se.     

A low-calorie diet improves endothelium-dependent vasodilation in obese patients with essential hypertension

BackgroundBoth obesity and hypertension are associated with endothelial dysfunction. The purpose of this study was to investigate the effects of a low-calorie diet on endothelial function in obese patients with essential hypertension.MethodsWe measured forearm blood flow (FBF) during intra-arterial infusion of acetylcholine (ACh; 7.5, 15, 30 μg/min), an index of endothelium-dependent vasodilation, and isosorbide dinitrate (ISDN; 0.75, 1.5, 3.0 μg/min), an index of endothelium-independent vasodilation, in obese patients with essential hypertension before and after 2 weeks on a low-calorie diet (800 kcal/d). The study included 11 obese hypertensive Japanese patients (mean body mass index, 30.8 ± 3.6 kg/m²). Fifteen healthy Japanese normotensive individuals were recruited as a control group.ResultsIn obese patients with hypertension, the response of FBF to ACh was attenuated compared to healthy individuals (P < .001). Caloric restriction reduced body weight from 77.5 ± 15.0 to 73.2 ± 13.5 kg (P < .01), the mean blood pressure from 118.4 ± 8.7 to 105.7 ± 8.5 mm Hg (P < .01), fasting plasma insulin from 85.8 ± 22.8 to 64.8 ± 27.0 pmol/L (P < .05), serum total cholesterol from 5.30 ± 0.76 to 4.67 ± 0.58 mmol/L (P < .05), and low density lipoprotein cholesterol from 3.80 ± 0.48 to 3.29 ± 0.44 mmol/L (P < .05). Basal FBF was similar before and after weight reduction. Caloric restriction enhanced the response of FBF to ACh (P < .05), but did not alter the response to ISDN. The intra-arterial infusion of N^G-monomethyl-l-arginine (8 μmol/min), a nitric oxide synthase inhibitor, decreased the enhanced ACh-induced blood flow response induced by caloric restriction.ConclusionsThe present findings suggest that the caloric restriction improves endothelial-dependent vasodilation through an increased release of nitric oxide in obese hypertensive patients.     

冠心病合并2型糖尿病患者的血清AGEs与内皮依赖性血管舒张功能关系探讨

目的　探讨冠心病合并 2型糖尿病 (2 - DM)患者内皮依赖性血管舒张功能与血清糖基化终产物(AGEs)水平变化及二者的关系。方法　选择 6 0例冠心病合并 2 - DM患者为治疗组 ,在冠心病综合治疗的基础上给予胰岛素或其他降糖药物控制血糖 ;另选 6 0例查体健康者为对照组。检测两组血清 AGEs、NO水平 ,采用 Jud-kins法进行选择性冠状动脉造影 ,高分辨超声技术检测肱动脉的血管舒张功能。结果　治疗组治疗前后血清AGEs、NO水平及内皮依赖性血管舒张功能均与对照组有明显差异 (P <0 .0 5 ,<0 .0 1) ,且治疗组治疗前后上述指标亦均有明显差异 (P <0 .0 1)。内皮依赖性血管舒张功能减弱程度与血清 AGEs水平呈负相关 (r =- 0 .39,P <0 .0 1) ,血清 NO水平与血清 AGEs水平呈负相关 (r=- 0 .31,P <0 .0 1)。结论　冠心病合并 2 - DM患者内皮依赖性血管舒张功能明显减弱 ,血清 AGEs水平明显升高 ,可能是 AGEs削弱了其内皮依赖性血管舒张功能。长期良好的血糖控制可降低冠心病合并 2 - DM患者血清 AGEs水平 ,增加血液中 NO水平 ,改善其内皮依赖性血管舒张功能     

Impaired endothelium-dependent cholinergic coronary vasodilation in patients with angina and normal coronary arteriograms.

The coronary vasomotor responses to selective infusion of graded concentrations (10(-6) to 10(-4) M) of acetylcholine into the left anterior descending artery were assessed by quantitative coronary arteriography in 24 patients with normal coronary arteriograms (12 patients with atypical symptoms and 12 patients with typical anginal pain) and 36 patients with coronary artery disease with different degrees of atherosclerosis of the left anterior descending artery. In the patients with normal coronary arteries and atypical chest pain, acetylcholine induced predominantly a vasodilator response, which was maximal during a 10(-5) M acetylcholine infusion. In contrast, in patients with coronary artery disease, acetylcholine caused dose-dependent vasoconstriction, which was observed even if the left anterior descending artery itself was smooth. Marked vasoconstriction was also induced in the patients with typical anginal pain and angiographically normal coronary arteries. In nine of these patients, this constrictor response was associated with anginal pain and electrocardiographic evidence of myocardial ischemia. Intracoronary administration of isosorbide dinitrate (1 mg) relieved the anginal pain and dilated all vessels. These data suggest that 1) patients with normal coronary arteriograms and angina pectoris manifest impairment of endothelium-dependent vasodilation similar to that observed in patients with overt coronary atherosclerosis; and 2) abnormal coronary vasoconstrictor responses resulting from this impairment may contribute to the pathogenesis of myocardial ischemia and angina in these patients.     

高血压伴冠心病患者冠状动脉狭窄与周围动脉功能关系的研究

目的分析冠状动脉的病变支数及狭窄程度与周围动脉弹性功能的关系。方法对88例高血压病患者与41例无高血压病临床怀疑冠心病的患者,在冠状动脉造影前后采用美国FDA批准的PULSEMETRIC动脉功能测定仪通过测定肱动脉脉搏图计算出反应血管弹性的参数,包括系统血管顺应性（SVC）、系统血管阻力（SVR）、肱动脉顺应性（BAC）及肱动脉阻力（BAR）,分析高血压伴及不伴冠状动脉病变者的动脉弹性的特点。结果（1）高血压组严重冠状动脉病变（冠状动脉病变〉12支以上）发生率[64．7％（57／88）]高于血压正常组[27．1％（11／41）,P〈0．05）;（2）高血压组的SVC[（0．85±0．10）ml／mmHg（1mmHg=0．133kPa）]、BAC[（0．047±0．011）ml／mmHg]明显低于非高血压组[SVC（1．17±0．11）ml／mmHg,BAC（0．063±0．010）ml／mmHg,均P〈0．05],高血压组的脉压则明显高于非高血压组[（78±20）mmHg比（47±19）ml／mmHg,P〈0．01];（3）高血压组内,动脉弹性有随冠状动脉病变加重而下降的趋势,而动脉弹性功能参数在不同的性别存在不同的变化;（4）当血压水平达到2～3级,SVC有随冠状动脉病变程度加重而降低的趋势。结论在高血压病患者中,无创方法测得的动脉功能参数在一定程度上可以反映其冠状动脉病变程度。     

Nitroglycerin-induced coronary vasodilation is not enhanced in patients with impaired endothelium-dependent dilation

Objectives. This study was designed to determine whether enhanced sensitivity to exogenous nitrovasodilators is present in the coronary arteries of patients with impaired endothelium-dependent dilation.Background. Animal studies have demonstrated that the dilator response to exogenous nitrovasodilators is exaggerated in the setting of endothelial dysfunction (diminished nitric oxide activity). Whether such relative hyperresponsiveness to exogenous nitrates occurs and is important in humans is unknown.Methods. We assessed coronary vasomotion in 110 patients (mean [±SD] age 56 ± 10 years) by serial intracoronary infusions of acetylcholine (10⁻⁸ to 10⁻⁶ mol/liter) to test endogenous nitric oxide and nitroglycerin (40 μg) to test responses to exogenous nitrovasodilators.Results. The vasomotor response to 10⁻⁶ mol/liter of acetylcholine differed between patients with (n = 95) and those without (n = 15) normal endothelial dysfunction (−21 ± 14% vs. 12 ± 8% respectively, p < 0.001). However, neither the dilator response to nitroglycerin (21 ± 14% vs. 18 ± 13%) nor the baseline diameter differed between those with endothelial dysfunction and normal function, respectively. There was no correlation between the magnitude of the dilator response to nitroglycerin and acetylcholine. The response to nitroglycerin was decreased with increasing age (r = −0.21, p = 0.03) but was not related to any other demographic factors or to the angiographic appearance of the vessel.Conclusions. The coronary vasodilator response to nitroglycerin is not significantly enhanced in patients with impaired endothelium-dependent dilation but decreases with increasing age. This finding provides indirect evidence that basal coronary tone is not increased in patients with endothelial dysfunction and that supersensitivity to exogenous nitrates is not clinically important in humans.     

辛伐他汀对原发性高血压并高胆固醇血症患者血管内皮依赖性舒张功能的影响

目的 :研究辛伐他汀对原发性高血压 (EH)并高胆固醇血症患者血管内皮依赖性舒张功能的影响。方法 :采用高分辨超声技术 ,对 2 4例EH并高胆固醇血症患者 (A组 )降脂前后和 2 0例血浆胆固醇水平正常的对照者 (B组 )血管内皮依赖性舒张功能进行检测。结果 :A组患者服用辛伐他汀 10mg治疗 8周后肱动脉血流介导性舒张较B组明显减弱 [(2 .99± 2 .2 4 ) %∶(7.0 1± 2 .73) % ,P <0 .0 1],且对硝酸甘油的反应差异亦有显著性意义[(8.2 8± 5 .12 ) %∶(12 .2 8± 4 .84 ) % ,P <0 .0 5 ]。血浆总胆固醇从 (6 .39± 0 .71)mmol L降至 (5 .2 3± 0 .33)mmol L ,同时肱动脉内皮依赖性舒张较治疗前明显改善 [(7.82± 1.2 9) %∶(2 .99± 2 .2 4 ) % ,P <0 .0 1],而治疗前后肱动脉对硝酸甘油的反应无显著性改变。结论 :EH并高胆固醇血症患者存在血管内皮依赖性舒张功能障碍 ;经辛伐他汀降胆固醇治疗后 ,受损的血管内皮依赖性舒张功能得到明显改善