可乐定治疗原发性顽固性高血压的疗效观察

目的 观察可乐定治疗原发性顽固性高血压的疗效及安全性.方法 选择原发性顽固性高血压患者为研究对象,入选患者加服可乐定片(75 μg/次,1次/8 h,1周后未达标,改为150 μg/次,1次/8 h),观察治疗前及治疗后每周诊室坐位血压、心率,检测治疗前后动态血压(ABPM)、血常规、肝肾功能、电解质、血脂及尿常规.结果 治疗后4周,诊室血压、ABPM的收缩压和舒张压均显著低于治疗前,差异有统计学意义(P＜0.01);根据诊室坐位血压,总有效率89.4％;根据ABPM,总有效率为80.8％.治疗后可出现心率下降、口干、乏力、嗜睡、便秘等不良反应,但无需停药.结论 可乐定对原发性顽固性高血压降压疗效确切,副反应可接受.同时不影响代谢,安全性好.     

原发性高血压患者血管紧张素转换酶基因多态性及危险因素的关系研究

目的　研究中国人群中原发性高血压患者血管紧张素转换酶 (ACE)基因多态性及其危险因素的关系。方法　对社区人群调查中确诊的 112例原发性高血压患者 ,和相同数量 ,性别、年龄相匹配的健康人询问与原发性高血压有关的因素 ,测量空腹血脂及坐位血压 ,应用聚合酶链反应(PCR)检测ACEI/D基因多态性。结果　两组ACE基因I/D多态性构成有显著性差异 (P <0 0 5 )。病例组DD基因型高于对照组 (30 4%vs18 8% ) ,其中男性组达 (34%vs14% ) ,均有显著差异 (P <0 0 5 )。结论　DD基因型似可作为原发性高血压 ,特别是男性原发性高血压的一种遗传易感指标 ;心脑血管病阳性家族史、向心性肥胖、高甘油三酯血症、DD基因型是原发性高血压的独立危险因素     

Management of essential hypertension

Hypertension, in spite of a very high prevalence, remains undertreated. This is not due to a lack of effective therapeutic modalities. Non-pharmacological treatments can be effective in many patients. If those treatments fail to reduce blood pressure sufficiently, the physician can choose between numerous classes of antihypertensive agents. However, interpatient variability in response to these agents is high, and use of multiple agents is frequently necessary. Thus, no single class has proven to be superior for the majority of patients. This article will review the different non-pharmacological and pharmacological methods available to treat hypertension, as well as the guidelines that are available to aid in proper selection of a treatment regimen.     

Homocysteine and essential hypertension

The authors examine the available clinical and experimental data supporting the view that homocysteine, an alternative risk factor of cardiovascular disease, may play a role in the pathogenesis of essential hypertension. The mechanism of this disease has not been elucidated, but it may be related to impairment of vascular endothelial and smooth muscle cell function. Therefore, the occurrence of endothelial dysfunction could contribute to alterations of the endothelium-dependent vasomotor regulation. Elevated homocysteinemia diminishes the vasodilation by nitric oxide, increases oxidative stress, stimulates the proliferation of vascular smooth muscle cells, and alters the elastic properties of the vascular wall. Thus, homocysteine contributes to elevate the blood pressure. Also it is known that elevated plasma levels of homocysteine could lead to oxidant injury to the endothelium. The correction of elevated homocysteinemia by administration of vitamins B12 and B6 plus folic acid, could be a useful adjuvant therapy of hypertension. However, further controlled randomized trials are necessary to establish the efficacy and tolerability of these potentially therapeutic agents.     

Management of essential hypertension

Hypertension, in spite of a very high prevalence, remains undertreated. This is not due to a lack of effective therapeutic modalities. Non-pharmacological treatments can be effective in many patients. If those treatments fail to reduce blood pressure sufficiently, the physician can choose between numerous classes of antihypertensive agents. However, interpatient variability in response to these agents is high, and use of multiple agents is frequently necessary. Thus, no single class has proven to be superior for the majority of patients. This article will review the different non-pharmacological and pharmacological methods available to treat hypertension, as well as the guidelines that are available to aid in proper selection of a treatment regimen.     

Labetalol in essential hypertension

Labetalol is an orally active adrenoreceptor-blocking drug which is a competitive antagonist of both alpha- and beta-adrenoreceptor sites. Thirty patients with essential hypertension were admitted to the study. The mean of initial systolic and diastolic blood pressures of these patients was 160/101 +/- 3/1 supine and 155/104 +/- 3/1 mm Hg standing, and the mean blood pressures at the end of the 16 week trial was 142/90 +/- 4/2 supine and 131/91 +/- 3/2 mm Hg standing. The average dose of labetalol was 546 mg: eight patients received a dose of 300 mg, seven a dose of 600 mg, six a dose f 900 mg, and two a dose of 1,200 mg. The patients who needed the highest doses of labetalol had an initial lowering of their blood pressures followed by a gradual increase despite the higher doses of labetalol. There was no significant change in the mean peripheral renin activity value. Side effects were reported by 18 of the 30 patients, but only 1 patient withdrew for this reason. Two patients were considered to be treatment failures. Overall, labetalol was found to be an effective antihypertensive agent in 15 patients.     

Bucindolol in essential hypertension

The effects of bucindolol a new nonselective beta blocker were studied after short-term dosing and for up to six months in eight patients with essential hypertension. Bucindolol 100 mg acutely lowered supine and erect systolic and diastolic pressure without orthostatic features and without increases or decreases in heart rate. Plasma noradrenaline increased, but plasma renin activity fell. Long-term dosing of 100-400 mg/day led to modest decreases in blood pressure. The duration of the hypotensive effect after multiple dosing ranged from six to ten hours. After long-term dosing there was evidence of marked nonselective beta blockade but not of alpha 1 blockade from the responses to intravenous isoprenaline and phenylephrine respectively. In six out of eight patients the plasma creatinine phosphokinase rose transiently above the normal range. The increase appeared to be of muscle origin and was associated with myalgia in one patient. Bucindolol is a nonselective beta blocker, possibly with other vasodilator properties. These do not appear to be mediated by alpha blockade.     

阿罗洛尔治疗原发性高血压

目的 :观察阿罗洛尔对轻、中度高血压的治疗效果。方法 :治疗对象 6 0例 (男性 38例 ,女性 2 2例 ,年龄 55a±s11a) ,给阿罗洛尔 10mg ,qd× 6wk。结果 :服用阿罗洛尔后 1～ 3wk血压、心率逐渐下降 ,血压从治疗前的 2 2 .3/ 12 .7kPa下降到wk4的 16 .9/ 10kPa ,wk 6的 16 .4 / 9.8kPa ,心率从治疗前的 80次·min- 1下降到wk 4的 6 8次·min- 1,wk6的 6 7次·min- 1,差异均有非常显著性意义 (P <0 .0 1) ,降低血压的总有效率为 85% ,对肝、肾功能及血常规无明显影响。结论 :阿罗洛尔是一种满意的降压药。     

伊贝沙坦治疗原发性高血压临床疗效

目的 :观察伊贝沙坦对原发性高血压患者降压的疗效及安全性。方法 :采用自身对照开放试验 ,选取 40例原发性高血压患者 ,服用伊贝沙坦 15 0mg·d-1,如 4wk无效加至 30 0mg·d-1,至 8wk。每 2wk随访BP ,HR ,并记录不良反应。结果 :经 8wk治疗 ,伊贝沙坦降压总有效率达 95 % ,平均SBP由 (146 3± 14 7)mmHg降至 (130 9± 11 0 )mmHg ,DBP由 (94 6± 15 2 )mmHg降至 (79 3± 6 8)mmHg ,P <0 0 5。整个治疗期间无明显不良反应发生。结论 :伊贝沙坦是一个安全、有效的降压药物     

The causes of essential hypertension

1 Confusion between the criteria for defining and diagnosing hypertension may have misled the search for the causes of hypertension.
2 The systematic approach of molecular genetics appears to offer the best chance of explaining hypertension, but the attractions are partly offset by the large numbers required, and unproven record of the genetic techniques in finding functional mutations in complex human disorders.
3 Part of the evidence for the polygenic nature of essential hypertension derives from the variable response to a large number of different anti-hypertensive agents. Systematic investigation of this variability may provide a basis for dividing patients into genetically more homogeneous sub-groups, within which smaller numbers will be required to detect the genes responsible for the susceptibility to hypertension.
4 The proportion of hypertensive patients with affected siblings has been studied in 6000 patients from Addenbrookes Hospital and local general practices. A recurrence risk for hypertension of∼3.5 was found.
5 Approximately two-thirds of patients have no known affected siblings. The next largest group, about one third, is patients whose siblings are all hypertensive. In a small group, <10% of all patients, half the siblings are hypertensive.
6 We conclude from these surprising findings that hypertension is not a continuous, multifactorial part of the normal blood pressure distribution. They suggest that several more single-gene disorders causing hypertension will be found. The sibships where all members are hypertensive are inconsistent with the segregation of Mendelian genetics and suggest the selection of some genes linked to hypertension at the time of gamete maturation.     

Pharmacotherapy of essential hypertension.

Practical clinical aspects of the evaluation and treatment of essential hypertension are reviewed. Drug therapy discussed includes diuretics, and as adjunctive therapy, sympathoplegic agents, peripheral vasodilators and beta blockers. Also covered are treatment of less common forms of essential hypertension, other forms of antihypertensive therapy, and the use of fixed combinations of antihypertensive drugs.     

The genetics of essential hypertension

Essential hypertension is an escalating problem for industrialized populations. It is currently seen as a 'complex' genetic trait caused by multiple susceptibility genes the effects of which are modulated by gene-environment and gene-gene interactions. Nevertheless, the success to date in identifying these susceptibility genes has been very limited. A number of candidates has been proposed, but demonstrating consistently the linkage or association with hypertension has been problematic. The data for angiotensinogen is undoubtedly the most extensive and meta-analysis has confirmed a significant association overall, although the risk contributed by this gene appears to be modest (odds ratio of 1.2). Identifying further genes - probably conferring even smaller attributable risks - represents a major challenge for future developments in this area. This contrasts markedly with the success that has been achieved in the past 5 years in solving the molecular genetics of a number of rare familial hypertension syndromes. The true incidences of some of these disorders may be higher than first appreciated, but it is still unclear if the genes for these syndromes also play a part in essential hypertension. A more complete understanding of the genetic basis of essential hypertension should be possible in the coming years using new strategies that take advantage of the information provided by the human genome project. This knowledge will irrevocably change the way we approach this disease in terms of its diagnosis, risk assessment for end-points such as stroke and heart disease, and the customised treatment that might be offered in the future.     

Treatment of benign essential hypertension

Summary Furosemide (Impugan^®) 12.5, 25 or 40 mg twice daily, has been compared as an antihypertensive with hydrochlorothiazide 12.5 mg twice daily and a placebo. A double blind, cross-over design was used with a run-in period of 4 weeks, preceding five 4-week periods of treatment with these compounds alone. There were 34 patients in the trial, 17 men and 17 women. Paired comparison showed that furosemide 25 or 40 mg twice daily and hydrochlorothiazide 12.5 mg twice daily had a similar hypotensive effect, irrespective of the initial blood pressure. Furosemide 40 mg twice daily and hydrochlorothiazide 12.5 mg twice daily caused a slight fall of blood pressure as compared with placebo (0.10>p>0.05, p<0.05). There was a distinct correlation between blood pressure and age. Serum K⁺ fell significantly during treatment, particularly with hydrochlorothiazide 12.5 mg twice daily, as well as with furosemide 25 or 40 mg twice daily. As compared with placebo, urinary output increased significantly after furosemide 12.5, 25 or 40 mg twice daily, but it rose only to a non-significant extent after hydrochlorothiazide. The fall of blood pressure and decrease in serum K⁺ were linearly related. There were only a few, mild side effects which did not necessitate discontinuation of the trial.     

Vascular abnormalities in essential hypertension

Arterial hypertension is a very common disease and an important risk factor for cardiovascular disease. Patients with arterial hypertension are characterized by functional and structural vascular abnormalities. Vascular endothelium plays a fundamental role in modulating vascular tone and structure. The physiological production of the relaxing factors including nitric oxide, prostacyclin and hyperpolarizing relaxing factors protects the vessel wall by antagonizing the first pathogenetic steps of atherosclerosis and thrombosis. Endothelial cells may also produce endothelium-derived contracting factors. The principal component of these contracting factors is endothelin-1, which promotes the growth of the smooth muscle cells and has a vasoconstrictive and blood pressure raising effect. Defective nitric oxide production is already detectable in normotensive offspring of hypertensive patients and young essential hypertensives. A dysfunctional endothelium due to reduced nitric oxide availability associated with an increased production of oxidative stress and vasoconstricting factors is considered as an early indicator of atherothrombotic damage and of cardiovascular events also in patients with arterial hypertension. Moreover, patients with arterial hypertension are also characterized by increased arterial stiffness. This parameter, known as a sign of cardiovascular risk since the 19th century, has been shown to be a predictor of adverse cardiovascular outcome and its measurement in hypertensive patients is suggested by the European guidelines for the diagnosis and treatment of hypertension.     

Oxidative stress in essential hypertension

A major cause for endothelial dysfunction in essential hypertension is decreased availability of nitric oxide (NO). Impairment in NO bioavailability is likely to be the consequence of multiple mechanisms affecting NO synthesis as well as NO breakdown. An alteration in the redox balance in endothelial cells leads to increased superoxide anion production and oxidative stress. This in turn not only exerts negative effects on vascular tone, but is also able to activate important mechanisms (such as platelet activity, leukocyte adhesion, vascular smooth muscle cell proliferation and expression of adhesion molecules) with an established central role in the pathogenesis of hypertensive target organ damage. As a consequence, a drug therapy able to restore NO availability in essential hypertensive patients would probably exert additional benefits, as compared to blood pressure lowering per se, in terms of prevention of target organ damage and improved prognosis of these patients. Unfortunately, as of today only the antagonists of the renin-angiotensin system and the calcium-channel blockers have shown some ability in this respect, whereas no longitudinal intervention study has been undertaken, so far, to prove that the restoration of NO bioavailability through an antihypertensive treatment may confer additional prognostic advantage to essential hypertensive patients.     

高血压病对左室功能的影响

目的 探讨高血压病患者心脏左室功能的改变。方法 应用超声心动图及组织多普勒显像（DTI）检测74例高血压病患者及94例正常对照者左室收缩及舒张功能。结果 高血压病组左室质量指数、跨二尖瓣血流频谱速度A及E／A比值和DTI频谱速度s、a及e／a比值较正常组有显著差异（P〈0．05）,但左室射血分数（LVEF）、跨二尖瓣血流频谱速度E和DTI频谱速度e在高血压病组及正常组间无显著差异（P〉0．05）;DTI的收缩期峰速度与LVEF和舒张期峰速度比值e／a与E／A在两组问均呈显著相关（P〈0．05）。结论 高血压病患者收缩期峰速度S及舒张晚期峰速度a增加,提示左室收缩功能增强,左室僵硬度增加,左房辅助泵功能增强;DTI能早期、敏感地发现高血压病患者收缩及舒张功能的改变。     

Sympathetic nerve biology in essential hypertension

1. Although the importance of sympathetic nervous activation in the pathogenesis of essential hypertension is well documented, the exact pathophysiology of the sympathetic nervous dysfunction present remains to be delineated. There are several possible explanations for the increased spillover of noradrenaline from the kidneys and heart to plasma, a key piece of evidence supporting the neurogenic basis of essential hypertension, in addition to the obvious one of an increased rate of sympathetic nerve firing. 2. The possibility that there may be an increase in the density of sympathetic innervation in human hypertension, well documented in the spontaneously hypertensive rat, is currently under investigation by us. 3. Adrenaline cotransmission is present in the cardiac sympathetic nerves of patients with essential hypertension, presumptive evidence of their exposure to high levels of stress and a possible basis for the observed increase in cardiac noradrenaline spillover, through presynaptic augmentation of noradrenaline release. 4. Phenotypic evidence exists also of faulty noradrenaline reuptake into the sympathetic nerves of the heart in essential hypertension, an abnormality that would amplify the sympathetic neural signal by impairing removal of noradrenaline from the synaptic cleft.     

Lisinopril dose-response relationship in essential hypertension

1. This was a multicentre, double-blind, parallel study in 216 patients with mild to moderate (supine diastolic blood pressure = 95-115 mm Hg) essential hypertension. 2. After a 4-week placebo washout, patients were randomized to placebo or lisinopril 1.25, 5.20 or 80 mg once daily for 6 consecutive weeks. Supine and erect blood pressure was measured 24 h postdose at the end of weeks -2, 0, 2, 4, and 6. 3. There was a linear dose-response relationship for both supine and erect blood pressure. Diastolic blood pressure reductions in the lisinopril 20 and 80 mg day-1 groups were significantly greater than in the placebo or lisinopril 1.25 and 5 mg day-1 groups. 4. Lisinopril, at doses up to 80 mg day-1, was well tolerated.