三种莨菪药对急性肾衰大鼠血流变性改变的影响

本文研究了油酸致大鼠急性肾衰时血液流变性的改变。观察了樟柳碱，东莨菪碱及山莨菪碱对这些改变的影响。结果表明，急性肾衰时，低切至高切变率时的全血粘度均明显增高，红细胞比积，血浆粘度及红细胞聚集指数也明显高于对照组。樟柳碱及东莨菪碱能降低血浆粘度、红细胞聚集指数及全血粘度；山莨菪碱能降低血浆粘度及红细胞聚集指数。结果说明，急性肾衰时血液的流变性有明显障碍，三种莨菪药均能改善急性肾衰时血液的流变性。     

风湿性关节痛患者血液粘滞性观察

目的：观察208例风湿性关节痛患者和60例健康人的血液粘滞性改变。方法：用XN－5型血液粘度计测定低、高切变率、全血比粘度、红细胞聚集指数、血浆比粘度及红细胞比积并进行分析。结果：患者五项指标均显著高于对照组，血浆比粘度、全血比粘度、红细胞聚集指数显著相关，红细胞比积无明显增高。结论：血液粘滞性增高引起血液流变性异常是风湿性关节痛发生的病理基础之一。     

血液透析对尿毒症患者血液流变性的影响

研究单次及长期维持血液透析时尿毒症患者血液流变性改变的影响。结果表明，单次血透后，红细胞比积明显升高，红细胞刚性明显降低；血浆粘度、红细胞聚集指数、Ｃａｓｓｏｎ粘度、血液屈服应力及低切至高切的全血粘度无明显改变。维持血透患者的红细胞比积、血浆粘度、红细胞聚集指数、Ｃａｓｓｏｎ粘度、血液屈服应力均无明显改变。进一步研究发现，单次血透后血浆渗透比明显降低．这可能是引起红细胞比积升高、红细胞刚性降低的原因之一。     

偏头痛的血瘀研究

对２０例偏头痛发作期、间歇期患者的血液流变性、血小板聚集进行跟踪检测。结果，头痛发作期、间歇期的全血比粘度、血浆比粘度、红细胞压积、红细胞电泳、血小板第一相、第二相聚集率均显著高于正常对照组，发作期与间歇期之间各项指标均无显著差异。全血粘度高切与红细胞压积、血小板第二相聚集率与红细胞电泳时间之间呈显著正相关。     

终末期肾病患者肾移植后血液流变性之变化

研究终末期肾病肾移植后血液流变性的改变并探讨其临床意义。结果表明，肾移植后肾功能正常时，低切至高切变率时的全血粘度明显增高，甚至高于正常人。全血粘度的升高主要与红细胞比积、血浆粘度、红细胞聚集指数、Ｃａｓｓｏｎ粘度的增高有关，与红细胞的变形能力及血液屈服应力无明显关系。肾移植后肾功能失活时，红细胞比积及Ｃａｓｓｏｎ粘度降低，使低切至高切变率时的全血粘度降低，但血浆粘度仍明显高于正常对照组。提示，肾移植后肾功能正常时，血液的流变特性明显障碍，血液粘度尤其是血浆粘度升高，这可能是肾移植后肾功能失活的重要发病机理，也是血管栓塞性合并症发生的病理基础。     

大鼠高脂血症与血液粘度关系研究

目的：研究血脂与全血粘度、血浆粘度及其相关因素的关系。方法：以高脂血症大鼠模型，大鼠饲以高脂饲料，连续7周测血脂。结果：血浆TG增加2倍，TC增加13．2倍，LDL增加51．8倍，而HDL无明显改变。随血浆脂质的升高，大鼠血浆粘度也显增加，而红细胞刚性指数、红细胞变形指数及红细胞聚集指数显下降；全血高、中、低切粘度，全血还原粘度，红细胞计数、红细胞压积及红细胞电泳时间均无明显改变。与此同时，血浆纤维蛋白溶酶活性降低而血小板聚集功能增高。结论：上述结果表明，高脂血症主要导致血浆粘度增加，纤维蛋白溶酶活性和血小板聚集功能异常改变。     

住院治疗男性冠心病患者血液流变性变化的特点

２８例男性住院治疗冠心病（ＣＨＤ）患者，接受１０～４０天流变药物的治疗，虽然患者比积明显低于对照组（Ｐ＜０．０５），而血浆粘度明显高于对照组（Ｐ＜０．０１），但患者表观全血粘度及红细胞聚集指数与对照组无显著区别。若采用固定比积（０．５０）的红细胞ＰＢＳ，悬液，患者血样的表观粘度则明显高于对照组（Ｐ＜０．０５或＜０．０１）；红细胞聚集指数也明显高于对照组（Ｐ＜０．０５）。结果表明，红细胞变形性明显减弱和聚集性显著升高是住院男性冠心病患者血液流变性异常的主要特点，并提示，改善红细胞流变性异常和降低血浆粘度对冠心病患者可能是一种有益的治疗措施。     

青紫型先天性心脏病患儿血液流变学和血小板聚集功能的变化

本文观察了45例青紫型先天性心脏病(CCHD)患儿血液流变学和血小板聚集功能的变化。结果显示:与对照组比较红细胞压积和全血粘度显著提高,红细胞聚集功能及刚性增强,变形运动能力减低,血小板聚集功能降低,纤维蛋白原减少,血浆比粘度增高。提示CCHD患儿存在着严重的血液流变学异常,不仅有血液粘度的变化,而且有血小板和红细胞的生理功能异常。本文对其临床意义进行了讨论。     

小儿紫绀型先天性心脏病血浆MDA和血液流变学变化

测定３５例青紫型先天性心脏病患儿红细胞、血浆丙二醛（ＭＤＡ）含量、红细胞膜微粘度及血液流变学指标。结果患儿红细胞、血浆ＭＤＡ、膜微粘度、全血粘度、经细胞比积、红细胞聚集指数、刚性指数均显著高于正常组；ＭＤＡ含量，膜微粘度、红细胞刚性指数、聚集指数及全血粘度之间均存在正相关关系。提示患儿红细胞脂质过氧化反应增强，导致膜流动性降低、红细胞变形性差，聚集性增加，可能是血液粘度增加较为主要的原因。     

天安冲剂对血液流变学的影响

本文研究了天安冲剂对血液流变学的影响。结果表明:天安冲剂明显降低红细胞压积和任何层流速度血液的全血比粘度,对血浆比粘度和纤维蛋白原也有所不同程度的降低,同时对血小板聚集具有明显的抑制作用。     

Antihypertensive Therapie und Fettstoffwechsel

Summary Hypertension, hyperlipidaemia and cigarette smoking are major risk factors in coronary heart disease. Since many antihypertensive drugs alter plasma lipid levels it is a subject of current discussion that these agents may increase associated coronary risk and therefore offset the beneficial effects of lowering blood pressure. The purpose of this paper is to review clinical and experimental data in the literature on the influence of antihypertensive drugs on lipid metabolism. The thiazides hydrochlorothiazide and chlorthalidone cause an elevation of plasma triglycerides and very low density lipoprotein (VLDL) but have little effect on total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL). The unspecific beta-blockers, e.g. propranolol, do not affect total cholesterol and LDL but increase total triglycerides and VLDL and decrease HDL. The changes of plasma lipids and lipoproteins caused by cardio-selective beta-blockers, e.g. atenolol and metoprolol, and unspecific beta-blockers with intrinsic sympathomimetic activity (ISA), e.g. oxprenolol and pindolol, appear to be qualitatively similar but less pronounced. The alpha₁-blocker prazosin reduces total triglycerides and slightly lowers total cholesterol. The concentration of VLDL plus LDL decreases while HDL may increase. Only very few studies have been reported on the effects of other antihypertensive drugs, e.g. clonidine, hydralazine, on plasma lipids. Several experimental studies reveal that antihypertensive agents exert direct effects on triglyceride and cholesterol metabolism. Although the pathophysiological mechanisms and the significance of the alterations of lipid metabolism induced by antihypertensive drugs are not yet clear, the following guidelines for the clinical use of these agents are recommended: (1) before initiating drug treatment in hypertensive patients, blood lipid levels should be measured to exclude a preexisting hyperlipidaemia, (2) during long-term therapy with antihypertensive agents, lipoprotein fractions should be controlled in order to reconsider the therapeutic regime if major alterations of blood lipid levels are observed.

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Abkürzungen VLDL Very Low Density Lipoprotein - LDL Low Density Lipoprotein - HDL High Density Lipoprotein     

Hypertension and concomitant diseases: a guide for evidence-based therapy

Hypertension remains one of the leading causes of morbidity and mortality in the United States. Numerous antihypertensive agents are available today, and most hypertensive patients suffer from concomitant diseases/conditions. Many of these diseases/conditions require appropriate selection of antihypertensive agents. It gets quite complex to pick the initial and additional antihypertensive agents that are simultaneously beneficial in the management of these comorbidities. The authors believe this guide will assist physicians in picking the right agent to achieve goal blood pressure recommended by the Joint National Committee (JNC). In this paper, the introduction section briefly outlines some aspects of the pathophysiology of hypertension. This is followed by subsections that identify commonly encountered diseases/conditions that coexist with hypertension, and a list of antihypertensive drugs to be used for these conditions in the order of preference. The suggested choices are based on evidence from clinical trials, for the most part, and in some cases based on mechanisms of action of the drugs. The list of choices is then followed by concise explanations or rationale, including citations for the clinical trials or other relevant sources. Such a systematic approach and use of a handy flow chart would enhance appropriate blood pressure control and patient compliance and, hopefully, make a little dent in the rate of hypertension-related cardiovascular morbidity and mortality.     

The role of the brain renin–angiotensin system in hypertension: Implications for new treatment

Hypertension affects 26% of adults and is in constant progress related to increased incidence of obesity and diabetes. One-third of hypertensive patients may be successfully treated with one antihypertensive agent, one-third may require two agents and in the remaining patients will need three agents for effective blood pressure (BP) control. The development of new classes of antihypertensive agents with different mechanisms of action therefore remains an important goal. Brain renin–angiotensin system (RAS) hyperactivity has been implicated in hypertension development and maintenance in several types of experimental and genetic hypertension animal models. Among the main bioactive peptides of the brain RAS, angiotensin (Ang) II and Ang III have similar affinities for type 1 (AT1) and type 2 (AT2) Ang II receptors. Following intracerebroventricular (i.c.v.) injection, Ang II and Ang III similarly increase arginine–vasopressin (AVP) release and BP. Blocking the brain RAS may be advantageous as it simultaneously (1) decreases sympathetic tone and consequently vascular resistance, (2) decreases AVP release, reducing blood volume and vascular resistance and (3) blocks angiotensin-induced baroreflex inhibition, decreasing both vascular resistance and cardiac output. However, as Ang II is converted to Ang III in vivo, the exact nature of the active peptide is not precisely determined. We summarize here the main findings identifying AngIII as one of the major effector peptides of the brain RAS in the control of AVP release and BP. Brain AngIII exerts a tonic stimulatory effect on BP in hypertensive rats, identifying brain aminopeptidase A (APA), the enzyme generating brain Ang III, as a potentially candidate target for hypertension treatment. This has led to the development of potent orally active APA inhibitors, such as RB150 — the prototype of a new class of centrally acting antihypertensive agents.     

Modification of aortic barorecptor resetting in the spontaneously hypertensive rat.

Aortic barorecptor function was studied in spontaneously hypertensive rats (SHR) of various ages and normotensive Wistar rats. The aortic arch was isolated and perfused, and the activity of the left aortic nerve was recorded. The threshold pressure to elicit barerecptor firing was 80-120 mmHg in normotensive Wistar rats. Resetting of barorecptors (threshold pressure 160-180 mmHg) was found in all untreated SHR of 35-70 wk of age. Resetting of barorecptors was prevented in SHR by starting treatment with antihypertensive agents at the age of 11 wk. Treatment of 32-wk old SHR with antihypertensive agents for 4-6 wk resulted in reversal of barorecptor resetting in 50% animals. The percentage of SHR showing complete reversal of resetting did not increase even when the duration of treatment was tripled. In 52- to 64-wk old SHR, treated with antihypertensive agents, reversal of baroceptor resetting was seen in only 30% animals. It was concluded that baroceptor resetting in SHR was secondary to hypertension. Hypertension, in turn, induced hypertrophy of the tunica media of the aorta. Histological studies showed a close correlation between aortic hypertrophy resetting. Aortic hypertrophy may, therefore, be one of the important factors involved in baroceptor resetting.     

Comparative effects of hydralazine and captopril on the cardiovascular changes in spontaneously hypertensive rats.

Vascular changes that develop during the course of blood pressure rise in spontaneously hypertensive rats (SHRs) can be modified by antihypertensive therapy. It is not known, however, whether there is selectivity in the structural response to specific antihypertensive drugs. This issue was examined by comparing the effects of a direct vasodilator (hydralazine) and a converting enzyme inhibitor (captopril) on morphologic aspects of the cardiovascular system. Male SHRs, 21 weeks of age, were given either hydralazine (HCl plus hydrochlorothiazide, captopril plus hydrochlorothiazide, or hydrochlorothiazide alone. Untreated age-matched SHRs and Wistar-Kyoto normotensive rats (WKYs) were used as controls. Animals were sacrificed at 27-28 weeks of age. Both hydralazine and captopril lowered significantly the blood pressure of SHRs, whereas hydrochlorothiazide alone was ineffective. The heart/body weight ratios were dramatically reduced in captopril-treated SHRs to below the level of WKYs; hydralazine induced only a very modest (5%) reduction, whereas the diuretic alone was ineffective. The morphology of the aortic intima improved dramatically in response to captopril and hydralazine and, to a lesser extent, hydrochlorothiazide alone. This effect becomes apparent within 6 weeks of treatment, and the only evidence of preexisting disease is the persistence of collagen in the subendothelium. Captopril and hydralazine, but not hydrochlorothiazide alone, reduce the thickness of the aortic media below that of normotensive controls. In addition, captopril and hydralazine improve the structure of small intrarenal vessels. There was a strong correlation between the relative effectiveness of the three pharmacologic agents in lowering blood pressure and in improving the changes of intrarenal vessels. These results highlight the capacity of antihypertensive therapy to arrest or reverse the structural sequelae of hypertension. In addition, they underscore the heterogeneity in the response of different components of the cardiovascular system, which, in part, reflects selectivity in the action of antihypertensive agents.     

美国糖尿病协会对糖尿病肾病的临床建议

美国糖尿病协会(ADA)基于循证医学证据，近期在Diabetes Care上发表了今年有关糖尿病肾病的临床建议，内容包括糖尿病肾病的自然病程，微量白蛋白尿的筛查，血糖及血压控制的作用，及降压药对糖尿病肾病的作用等，并提供了这些方面的循证医学证据。本文对此作一介绍。     

Targeting Ouabain- and Adducin-dependent mechanisms of hypertension and cardiovascular remodeling as a novel pharmacological approach

Essential hypertension is a heterogeneous multifactorial syndrome associated with a high cardiovascular risk. A multiple choice of antihypertensive drugs is available; however, a high individual variability to the antihypertensive therapy is still responsible for a modest reduction of the CV risk and not satisfactory control of blood pressure levels. The success of future hypertension treatment will depend upon the understanding of the genetic molecular mechanisms operating in subsets of patients, and the ability of new drugs to specifically correct such alterations. Two mechanisms, among others, are involved in determining the abnormalities of tubular Na(+) reabsorption observed in essential hypertension: the polymorphism of the cytoskeletal protein alpha-adducin and the increased circulating levels of endogenous ouabain (EO). Both lead to increased activity and expression of the renal Na-K pump, the driving force for tubular Na transport. Morphological and functional cardiovascular alterations have also been associated with adducin and EO. Rostafuroxin is a new oral antihypertensive agent able to selectively antagonize adducin and EO hypertensive and molecular effects. It is endowed with high potency and efficacy in reducing blood pressure and preventing organ hypertrophy in animal models representative of both adducin and EO mechanisms. At molecular level, in the kidney, Rostafuroxin normalizes the enhanced activity of the Na-K pump induced by adducin mutation and antagonizes the EO triggering of the Src-EGFr-dependent signaling pathway leading to renal Na-K pump, and ERK Tyrosin phosphorylation and activation. In the vasculature, it normalizes the increased myogenic tone caused by ouabain. A very high safety ratio and an absence of interaction with other mechanisms involved in blood pressure regulation, together with initial evidence of high tolerability and efficacy in hypertensive patients, indicate Rostafuroxin as the first example of a new class of antihypertensive agents designed to antagonize adducin and EO-hypertensive mechanisms. Currently, a phase II multicenter European clinical trial is ongoing for providing the proof of concept that such a compound is effective in the subset of patients where these two mechanisms are at work.     

Long-term effects of captopril and atenolol in essential hypertension

Fifty patients with mild or moderate essential hypertension were randomized (double-blindly) to treatment with either captopril (n = 26) or atenolol (n = 24). Their mean supine diastolic blood pressure after placebo was 100-125 mmHg. The study included an initial dose finding phase (12 weeks) during which the dosages of captopril and atenolol were increased stepwise every second week in order to obtain normotension (supine diastolic blood pressure less than 95 mmHg). Hydrochlorothiazide was added when necessary. During the second phase of the study the patients were followed on active treatment for 2 years. After the initial 12 weeks of active treatment, recumbent and standing blood pressures had fallen significantly both in the captopril group (by 31/20 and 33/19 mmHg, p less than 0.001) and in the atenolol group (by 24/18 and 30/20 mmHg, p less than 0.01 (systolic), p less than 0.001 (diastolic)). The antihypertensive effect was maintained in both groups during long-term treatment. The antihypertensive effect of both agents was potentiated to the same extent by addition of hydrochlorothiazide. Side-effects were few and mild. It can be concluded that both captopril and atenolol are safe and effective antihypertensive drugs.     

中医治未病思想结合降压药物预防老年高血压患者肾损害疗效观察

目的 观察老年高血压在中医治未病思想下应用降压药物治疗对肾损害的预防作用。方法 选取2017年1月~2018年8月我院收治的老年高血压患者92例,采用随机数表法分为两组,各46例。对照组单纯予以降压药物干预,观察组应用降压药物+中医未病思想干预。比较两组血压、肾功能[尿微量白蛋白（UmAlb）、肌酐清除率（Ccr）及尿β2-微球蛋白（Uβ2-MG）]。结果两组干预2个月血压水平均较治疗前降低,且观察组降幅大于对照组,差异有统计学意义（P＜0.05）;观察组干预2个月UmAlb、Uβ2-MG低于对照组,Ccr高于对照组,差异有统计学意义（P＜0.05）。结论 针对老年高血压患者,应用中医治未病思想与降压药物进行干预利于降低血压水平,预防肾损害。     

糖尿病肾病与血液粘度

为研究糖尿病肾病患者血液粘度的改变，对不同病程度的糖尿病肾病患者血液粘度进行了观察。结果显示，大量白蛋白尿组患者高切变率（２４０ｓ－１）和低切变率（４８ｓ－１全血粘度增多明显低于正常白蛋白尿组（Ｐ＜００５，Ｐ＜００１），其红细胞压积也显著低于正常白蛋白尿组（Ｐ＜００１）。微量白蛋白尿组血液粘度和红细胞压积与正常白蛋白尿组比较均无显著差异。提示糖尿病肾病患者随病程进展出现肾性贫血而致红细胞压积减小，全血粘度降低。抗凝剂的使用也是影响血液粘度的因素之一