Hepatopulmonary syndrome.

The hepatopulmonary syndrom occurs when pulmonary microvacular dilatation causes hypoxemia in cirrhosis. It is found in between 15-20% of patients with chronic liver diseases and should be considered in the differential diagnosis of dyspnea or abnormal arterial oxygenation in this group. The presence of HPS appears to significantly increase mortality in affected patients with cirrhosis. The mediators of intrapulmonary vasodilatation and HPS are not fully characterized although pulmonary nitric oxide overproduction appears to be a key event in human and experimental models. Contrast echocardiography is the best screening test for pulmonary vasodilatation. Currently there are no effective medical therapies for HPS, although liver transplantation results in reversal of HPS in most cases. However, mortality is higher in patients with HPS undergoing transplantation relative to those without HPS.     

坎地沙坦联合辛伐他汀对高胆固醇血症高血压患者血管内皮功能的影响

目的观察他汀类调脂药物辛伐他汀联合使用血管紧张素Ⅱ受体拮抗剂(ARB)坎地沙坦对伴有高胆固醇血症的高血压患者血管内皮功能和炎症因子的影响。方法采用自身对照研究,给予46例伴有高胆固醇血症的高血压患者坎地沙坦4mg/d结合膳食治疗,8周后加服辛伐他汀每晚20mg。服药治疗前、8周以及16周结束时采用高分辨率超声系统检测肱动脉血流介导的血管舒张反应(FMD)评价血管内皮功能,并抽血比较血胆固醇、三酰甘油、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、血糖、血胰岛素、高敏C反应蛋白水平变化。结果坎地沙坦可以显著降低血压,加服辛伐他汀后血脂明显下降,血压没有进一步下降。联合治疗较单用坎地沙坦能进一步改善内皮依赖的血管舒张功能。结论辛伐他汀联合应用血管紧张素Ⅱ受体拮抗剂坎地沙坦可以进一步改善伴有高胆固醇血症的高血压患者的内皮功能。     

非对称性二甲基精氨酸对人阻力血管EDVD的抑制作用

目的探讨非对称性二甲基精氨酸(ADMA)对人离体阻力血管环内皮依赖性舒张(endothelium-dependent vasodilatation,EDVD)的抑制作用。方法在血液透析患者行动-静脉内瘘成形术时留取桡动脉,制备血管环,用机械法去内皮并设立内皮存在组和内皮缺失组。应用离体血管张力记录仪观察2组血管环在不同质量浓度ADMA(10-7mol/L、10-6mol/L、10-5mol/L、10-4mol/L和10-3mol/L)作用下张力的变化。内皮存在组用10-5mol/L苯肾上腺素(phenylephrine,PE)引发血管环收缩,再用质量浓度为10-5mol/L的乙酰胆碱(ACh)引发EDVD,然后用不同质量浓度ADMA处理,观察ADMA在内皮存在情况下对ACh所引起EDVD的抑制作用。内皮缺失组用质量浓度为10-5mol/L的PE引发血管环收缩后,再用质量浓度为10-7mol/L的硝普钠(SNP)引发非内皮依赖性血管舒张(EIVD),然后用不同质量浓度ADMA处理,观察ADMA在内皮缺失情况下对SNP引起EIVD的抑制作用。结果内皮存在组用10-5mol/L的ACh处理可使67.10%±18.63%因PE(10-5mol/L)引起收缩的血管舒张,ADMA对ACh引起的EDVD呈浓度依赖性抑制作用,相对收缩幅度依次为EDVD幅度的7.32%±8.60%(10-7mol/L)、20.03%±13.49%(10-6mol/L)、29.93%±11.78%(10-5mol/L)、43.30%±11.29%(10-4mol/L)和80.21%±18.16%(10-3mol/L)。在内皮缺失组,ADMA对SNP引起的EIVD呈微弱的抑制作用,且不表现为浓度依赖性。相对收缩幅度为EIVD的2.76%±1.98%(10-7mol/L)、2.27%±1.82%(10-6mol/L)、3.38%±2.99%(10-5mol/L)、3.59%±3.66%(10-4mol/L)和4.16%±3.67%(10-3mol/L)。结论ADMA可以有效地抑制ACh引发的EDVD反应,该抑制作用呈浓度依赖性和内皮依赖性。     

Flow-mediated dilation and gender in patients with coronary artery disease: arterial size influences gender differences in flow-mediated dilation

BACKGROUND: The risk of atherosclerosis and its complications differs between male and female subjects. This is probably associated with gender differences in endothelial function as reflected by endothelium-dependent vasodilation. The aim of the study was to compare flow-mediated dilatation (FMD) in males and females with coronary artery disease (CAD), and to determine factors that might potentially influence FMD. METHODS: Ninety-six patients with stable CAD (CCS II-III): 76 males (mean age: 57.7 +/- 10 years) and 20 postmenopausal females (mean age: 60.1 +/- 10 years) were included into the study. Clinical data, pharmacotherapy, concomitant diseases, and FMD were all assessed. FMD was measured with high-resolution ultrasound as the percent change of brachial artery diameter (BAd) after a 3-minute occlusion (%FMD), and following the administration of 0.4 mg sublingual nitroglycerin (%NTG-MD). RESULTS: The percentage of FMD was significantly decreased (P < 0.05), and BAd was significantly larger (P < 0.001) in males as compared to females. Clinical data, pharmacotherapy, and concomitant diseases were comparable in the study groups.In all subjects examined, %FMD was related to BAd (r =-0.415, P < 0.001) and the percentage of ejection fraction (EF%) (r = 0.325, P < 0.01) in the univariate analysis, and to BAd only (r =-0.343, P < 0.01) in the multivariate analysis. The percentage of nitroglycerine-mediated vasodilatation (NTG-MD) correlated negatively with BAd (r =-0.430, P < 0.001), and positively with EF% (r = 0.334, P < 0.01) in the univariate analysis, and with BAd (r =-0.288, P < 0.05) in the multivariate analysis. Index %FMD x BAd was comparable for male and female subjects. CONCLUSIONS: Males and postmenopausal females with CAD show differences in endothelium-dependent vasodilatation that seem to secondarily result from differences in the BAd. Objective comparison of %FMD is only possible between patients with the same brachial artery size.     

Hepatic lipase promoter C-480T polymorphism is associated with serum lipids levels, but not subclinical atherosclerosis: The Cardiovascular Risk in Young Finns Study

The common C‐480T polymorphism (rs1800588) of the hepatic lipase gene (LIPC) has been associated with high‐density lipoprotein (HDL) cholesterol, atherosclerosis, and coronary artery disease. In this study, we examined whether the polymorphism is associated with serum lipid and lipoprotein concentrations, as well as with subclinical atherosclerosis in Young Finns. The participants comprised 2041 men and women (aged 24–39 years) enrolled in the Cardiovascular Risk in Young Finns Study with complete data concerning the rs1800588 polymorphism and serum lipids concentration. All participants underwent an ultrasound examination for brachial artery flow‐mediated vasodilatation (FMD) and carotid artery intima‐media thickness (IMT) measurement. The marker of arterial elasticity, carotid artery compliance (CAC), was also calculated by means of ultrasound and concomitant brachial blood pressure measurements. In all subjects, serum total cholesterol (p < 0.001), HDL cholesterol (p = 0.006), apolipoprotein AI (apoAI, p < 0.001), and triglyceride (p = 0.009) concentrations increased according to rs1800588 genotype in the order CC, CT, and TT. The same order applied only to apoAI after adjustment for age, body mass index, systolic and diastolic blood pressure, smoking, alcohol consumption, physical activity, diabetes, hypertension, contraceptive hormone use in women, and concentrations of glucose, insulin and C‐reactive protein in men and women separately (p = 0.007 and p = 0.003, respectively). The polymorphism was also associated with HDL cholesterol, total cholesterol, and triglyceride levels in women (adjusted p = 0.004, p = 0.007 and 0.02, respectively), but not in men (p was not significant for all). No significant association between the rs1800588 and brachial FMD, carotid IMT, or CAC was found among the entire study population or among women or men separately, with or without adjustment for the above‐mentioned factors. The rs1800588 is associated with serum lipid and apolipoprotein concentrations, especially in women, but does not seem to be a determinant of brachial artery FMD, carotid IMT, or CAC in young healthy adults.     

度洛西汀对大鼠胸主动脉环舒张功能的影响

目的研究度洛西汀(DLX)对血管舒张功能的影响并探讨其作用机制。方法采用离体血管环灌流装置,观察DLX对大鼠胸主动脉环的作用及不同工具药的影响。结果 DLX对KCl(30 mmol.L-1)和NE(1μmol.L-1)预收缩的血管环具有浓度依赖的舒张作用,对内皮完整和去内皮血管环舒张作用无差异,该舒张作用为非内皮依赖性。在KCl预收缩基础上,加入钾通道阻断剂格列苯脲Gli(10μmol.L-1)、四乙胺TEA(10 mmol.L-1)、氯化钡BaCl2(1 mmol.L-1)、四氨基吡啶4-AP(1 mmol.L-1)和5-HT2受体阻断剂赛庚啶(1μmol.L-1)均不能抑制DLX的舒血管效应;α1受体阻断剂哌唑嗪(1μmol.L-1)组对DLX舒血管作用有抑制作用。在无钙液中,DLX可以明显抑制NE和CaCl2收缩血管的作用。结论 DLX能够浓度依赖性的舒张血管,其机制可能与抑制经由血管平滑肌细胞膜VDC和ROC通道的钙离子内流,拮抗α1受体以及抑制胞质内钙离子释放有关。     

Robert F. Furchgott,Nobel laureate (1916–2009) – a personal reflection

Robert F. Furchgott, pharmacologist and joint winner of the Nobel Prize for Medicine or Physiology (1998) died on the 12th of May 2009 aged 92. By unlocking the astonishingly diverse biological actions of nitric oxide, Furchgott leaves behind a rich legacy that has both revolutionized our understanding of human physiology and stimulated new and exciting opportunities for drug development in a wide range of pathological conditions. In this article, William Martin, who worked with Furchgott for 2 years (1983–1985), following the exciting discovery of endothelium-derived relaxing factor/nitric oxide, pays tribute to his close friend and colleague.     

四乙酰葛根素对离体大鼠胸主动脉环作用初步研究

目的观察四乙酰葛根素（Tp）对离体大鼠胸主动脉环的作用以及作用机制。方法采用大鼠离体胸主动脉环灌流装置,观测四乙酰葛根素对重酒石酸去甲肾上腺素（NA）和氯化钾（Kcl）预收缩主动脉环张力的影响。结果四乙酰葛根素对去甲肾上腺素预收缩主动脉环有明显的舒张作用,与空白对照相比,具有显著性差异（P〈0．01）;由KCl引起主动脉环预收缩,Tp与空白对照相比,具有统计学差异（P〈0．01）,对内皮完整血管环的舒张作用明显强于去内皮血管环（P〈0．01）;Tp对NA在无钙液及正常钙液所致离体血管环收缩的舒张作用不明显（P〉O．05）。结论四乙酰葛根素的舒血管作用与受体依赖性钙通道和电压依赖性钙通道均有关,并且其舒血管作用可能与内皮有一定关系。     

山楂叶总黄酮对家兔实验性动脉粥样硬化的影响

目的研究山楂叶总黄酮对家兔实验性动脉粥样硬化的影响。方法饲喂高脂饲料建立动脉粥样硬化家兔模型,测定家免血清总胆固醇（Tc）、甘油三酯（TG）、高密度脂蛋白（HDL-c）及低密度脂蛋白（LDL—c）含量。取主动脉做病理检查,免疫组化分析Bax、Bcl-2在粥样硬化斑块中的表达。结果病理检查结果表明,山楂叶总黄酮能明显减轻模型家兔动脉粥样硬化性损伤。山楂叶总黄酮能降低动脉粥样硬化家免血清TG含量,升高HDL-C含量。免疫组化显示,与模型组比较,山楂叶总黄酮组Bax的表达显著降低,Bcl-2的表达显著升高,而且Bax／Bcl-2的比值降低。结论山楂叶总黄酮通过降低血脂,调节Bax、Bcl—2表达而发挥抗家兔实验性动脉粥样硬化作用。     

Vasorelaxation Mechanisms of Quercetin in Rat Arteries

Objective To investigate the effects of quercetin, a kind of flavonoids, on the vasodilating actions. Methods Rat artery ring strips were pretreated with 5 gM NE and then, quercetin was applied. The chamber solution was kept at 36.5℃ and oxygenated with 95% 02 and 5% CO2. Results Quercetin （0.1 to 100 μM） relaxed NE-induced constriction in a concentration-dependent manner. NO synthesis inhibitors, L-NMMA and L-NAME, at 100 jaM significantly reduced the quercetin （100 μM）-induced vasorelaxation. The quercetin （100 μM）-induced vasorelaxation was attenuated by nicardipine （0.1 μM）, and decreased in Ca2＋-free solution strongly. Quercetin also dilated the vasoconstriction induced by KCI （60 raM）. Under KCl-induced vasoconstriction, the quercetin-induced vasorelaxation was attenuated by different types of PK-C inhibitors, namely G86983 （α-,β-,γ-,δ and ζ-sensitive） and Ro-31-8425 （α-,β-,γ- and ε-sensitive）. G66983 produced a stronger relaxing effect than Ro-31-8425. In rat mesenteric artery during exposure to indomethacin and L-NMMA, the quercetin-induced relaxation was not significantly reduced by high K＋ or TEA. Conclusions Quercetin vasodilates the vascular smooth muscle mediated by endothelium-dependent （NO （inhibition of the Ca2＋ channels and modulation of PK-C）. synthesis inhibition） and -independent mechanisms