Quantitative evidence of peripheral conversion of angiotensin within the human leg: effects of local angiotensin-I administration and angiotensin-converting enzyme inhibition on regional blood flow and angiotensin-II balance across the leg

Summary The renin-angiotensin system relevantly contributes to the maintenance of systemic vascular tone and there is experimental evidence that large amounts of angiotensin-converting enzyme (ACE) are present in peripheral vascular tissues, including resistance vessels. To determine and quantify peripheral vascular conversion of angiotensin-I (ANG-I) to angiotensin-II (ANG-II) across the human leg, the response of regional blood flow to local regional intra-arterial infusion of ANG-I and changes in associated ANG-I1 balance were evaluated during ANG-I infusion and following additional ACE inhibition. Ten sodium-loaded healthy men were enrolled in the study. Following cannulation of both femoral arteries and the right femoral vein, leg blood flow was determined (indocyanine-green dye-dilution method) at baseline conditions and during constant intra-arterial infusion of haemodynamically ineffective doses of ANG-I as well as following concomitant intra-arterial administration of low doses of the non-sulfhydril ACE inhibitor cilazapril. From the transfemoral arterio-venous differences in ANG-II plasma concentrations and the corresponding regional blood (plasma) flow, the ANG-II balance across the leg was calculated. Systemic blood pressure did not change throughout the trial, indicating that no major systemic effects were present during ANG-I infusion or concomitant ACE inhibition. Moreover, arterial ANG-II plasma concentrations were not significantly changed by ANG-I infusion. Leg blood flow decreased to below baseline values following ANG-I infusion, increasing again then in a dose-dependent manner during concomitant cilazapril administration. The calculated baseline ANG-II balance across the leg revealed a net extraction in 6 out of 10 subjects and a net ANG-II formation in 4. Following ANG-I, a shift towards net ANG-II formation or decrease in extraction was seen in 8 subjects, while 2 had no change in ANG-II balance.During concomitant ACE inhibition, ANG-II balance was again shifted towards net extraction or reduced formation. Our results confirm that, in man, considerable regional arterio-venous differences in ANG-II plasma concentrations are present, resulting in either net transfemoral extraction or net formation of the peptide. It is suggested that systemic vascular conversion of circulating ANG-I might contribute to the maintenance of peripheral vasuclar tone in man. Send offprint requests to S. Gasic at the above address     

太极通天液治疗血管性痴呆的疗效评价

目的：评价太极通天液治疗血管性痴呆的临床疗效。方法：随机将148例血管性痴呆分为太极通天液治疗组和丹参口服液对照组，另接应用韦氏成人智力量表评分，将血管性痴呆组分为3个亚组：即80－89分组，70－79分组和70分以下组，观察期为3个月。结果：太极通天液治疗前后WAIS－RC评分与对照组比较，80－89分组和70－79分组均有统计学差异（P＜0．05），而70分以下组无统计学差异（P＞0．05），结论：太极通天液对血管性痴呆有较好的治疗效果，且与痴呆病情程度有关。     

麝香酮对易卒中型肾血管性高血压大鼠血浆内皮素和脑血管重塑的影响

目的观察麝香酮对易卒中型肾血管性高血压大鼠(RHRSP)血浆内皮素(ET)和脑动脉结构改变的影响。方法雄性RHRSP自术后第9周始分成两组:高血压组(n=12)和麝香酮治疗组(n=12),并以年龄、性别、数量相同的正常假手术组作对照,测量收缩压(SBP)和血浆ET含量,显微镜下观察血管形态改变,计算机图像分析血管外径、中膜厚度、管腔内径、中膜面积和壁腔比。结果12周时麝香酮组的SBP、ET水平比高血压组低(P<0.05)。镜下观察发现麝香酮组血管形态损害比高血压组轻。麝香酮组血管外径、血管内径、管壁厚度均大于高血压组(P<0.05),壁腔比则小于高血压组(P<0.05)。大脑中动脉平滑肌细胞面积较高血压组大,但两者间差异无统计学意义(P>0.05)。结论麝香酮治疗可轻度降低RHRSP的SBP和血浆ET水平,并能一定程度上改善其血管重塑。     

A double-blind cross-over study of nifedipine retard in patients with Raynaud's phenomenon

Summary The effectiveness of nifedipine retard as a treatment for Raynaud's phenomenon was assessed in 15 patients in a placebo controlled double blind study. An associated connective tissue disease was evident in 7 patients. Changes in finger and forearm blood flow (venous occlusion plethysmography), digital skin temperature and digital systolic pressure were measured acutely before and after a 2-week treatment period. Subjective assessment of efficacy was based on patient diary data. In addition alpha₂-adrenoceptor density on platelets was measured before and after chronic nifedipine therapy in both the patient group and in an age-and-sex-matched control group. No significant haemodynamic changes were observed. Nifedipine retard significantly reduced the frequency (p<0.05) with no change in either the duration or severity of vasospastic attacks. Side effects were commono following nifedipine retard. A reduction in alpha₂-adrenoceptor density on platelets was observed in patients compared to a control group (p<0.05). Alpha₂-adrenoceptor density was unchanged following a 2-week treatment period with nifedipine retard. This study concludes that nifedipine retard is not effective in the treatment of Raynaud's phenomenon over a short time course. Patients with Raynaud's phenomenon have reduced alpha₂-adrenoceptor densities on their platelets.     

低强度激光照射诱导大鼠胸主动脉金属硫蛋白的生成

目的：观察低强度红激光照射对大鼠脑主动脉金属硫蛋白（metallothionein,MT)生成的影响，探讨激光照射的细胞保护机制。方法：取24只大鼠的胸主动脉，将其制成厚度为0．5mm的薄片，置于含10％胎牛血清Krebs-Henseleit液6孔培养板，经95％O2－5％CO2、37℃孵育。设对照组及3个实验组，对照组不照射激光，3个实验组分别以功率密度为3、6和12J／cm^2的632nm波长的激光照射。采用竞争性RT－PCR法测定胸主动脉内MT的mRNA水平变化，以^109Cd牛血红蛋白饱和法测定MT的含量。结果：3个实验组MT1 mRNA水平分别比对照组增加175％（P＞0.05)、418．6％（P＜0．05）和668．2％（P＜0．01）；MT2 mRNA水平分别比对照组增加163．9（P＞0．05）、615％、（P＜0．01）和1087％（P＜0．01）；相应的MT蛋白含量分别比对照组增加142．8％（P＜0．05）、170．8％（P＜0．05）和142．1％（P＜0．05）。     

Vascular cell adhesion molecule-1 modulation by tumor necrosis factor in experimental allergic encephalomyelitis

Anti-tumor necrosis factor (TNF) antibodies inhibit passively transferred experimental allergic encephalomyelitis (EAE) in SJL mice. The possibility that this occurs through interference in TNF's upregulation of endothelial cell adhesion molecules was investigated. Expression of both vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on spinal cord vessels increased during EAE. The upregulation of VCAM-1 was markedly reduced or prevented by anti-TNF treatment. Leukocytic infiltration was 15-fold lower in anti-TNF-treated than diseased animals. Spinal cord endothelial expression of VCAM-1, though not ICAM-1 or fibronectin, positively correlated with the extent of T cell, B cell or monocyte infiltration in each animal.     

糖皮质激素受体阻断对烫伤大鼠肺、肾血管壁通透性变化的影响

我们以糖皮质激素受体（ＧＲ）的竞争性拮抗剂ＲＵ３８４８６（简称ＲＵ４８６）阻断大鼠体内的ＧＲ，并通过检测肺、肾组织匀浆中荧光标记白蛋白的含量，观察了烫伤后１２ｈ大鼠肺、肾血管壁通透性的变化以及阻断ＧＲ对这种变化的影响。结果显示：烫伤后１２ｈ，大鼠肺、肾组织匀浆中荧光标记白蛋白含量明显高于对照组（肺：Ｐ＜０．０５；肾：Ｐ＜０．００１）；阻断ＧＲ后再烫伤大鼠，其肺、肾组织匀浆中的荧光白蛋白含量又显著高于烫伤组（Ｐ＜０．０５）。提示：①烫伤后１２ｈ，大鼠肺、肾血管壁通透性明显升高。②ＧＲ减少可加重烫伤所致的血管壁通透性升高，并可逆转内源性糖皮质激素（ＧＣ）稳定血管壁通透性的作用。     

同型半胱氨酸对大鼠血管平滑肌细胞胶原蛋白合成及其mRNA表达的影响

目的 :观察同型半胱氨酸 ( Hcy)对血管平滑肌细胞 ( VSMCs)胶原合成的影响 ,并探讨其作用机制。方法 :本实验采用体外培养的大鼠 VSMCs,加入不同浓度的 Hcy,通过 3 H-脯氨酸掺入、α1[ ]型胶原测定观察 Hcy对 VSMCs胶原合成的影响 ,并通过半定量 RT- PCR检测其对 α1[ ]型胶原 m RNA表达的影响。结果 :Hcy促进 VSMCs的胶原合成及 α1[ ]型胶原 m RNA表达 ,并呈剂量依赖效应。结论 :Hcy促进 VSMCs的胶原合成 ,可能是通过促进 α1[ ]型胶原 m RNA表达实现的。提示 Hcy促进胶原合成可能是动脉粥样硬化的发病机制之一