依那普利对高血压病左心室肥厚患者QT离散度的影响

目的　研究长期使用依那普利治疗高血压病合并左心室肥厚时对QT离散度的影响。方法　 2 4例高血压病 (EH)合并左心室肥厚 (LVH)者 ,服用依那普利 (10mg 1次 /d) 3年 ,用标准 12导联心电图测量QT间期、校正的QT间期 (QTc)、QT间期离散度 (QTd)及校正的QT间期离散度 (QTcd) ;用二维及M型超声心动测定有关心血管参数。结果　依那普利不仅能迅速降压 ,而且能逐渐降低左心室重量指数 (LVMI)达 3 9% (P <0 .0 0 1) ,显著提高左心室泵血功能 ;同时明显缩短QTd[从 (61± 2 1)到 (41± 15 )ms、QTcd从 (67± 2 7)到 (46± 18)ms] ,QT及QTc也同样明显缩短。结论　长期用依那普利治疗EH合并LVH ,能明显使患者左心室肥厚回缩 ,提高其左心室收缩功能 ,并通过降低QTd及QTcd ,进一步降低室性心律失常发生率 ,从而改善预后。     

Amlodipine with enalapril therapy in moderate-severe essential hypertension

The efficacy and toleration of amlodipine (10 mg once daily) was compared with placebo in a four-week double-blind parallel group two-centre study in 38 patients who were receiving enalapril. Patients were moderate to severe hypertensives whose blood pressure was not adequately controlled by enalapril (5-10 mg once daily) (diastolic blood pressure greater than 95 mmHg after four weeks). Results are expressed as the mean difference, in baseline to final changes, between the two treatment groups. At the end of the double-blind period amlodipine patients had significantly greater decreases in supine (-19.4/-10.2 mmHg, P less than 0.001/P less than 0.001) and standing (-16.2/-10.2 mmHg, P less than 0.005/P less than 0.001) blood pressures than the placebo group. There was a greater fall (P = 0.005) in standing diastolic blood pressure at the UK centre (-17.1 mmHg) than in Denmark (-11.2 mmHg). However, pooling the standing diastolic blood pressure data from the two centres gave an overall significant mean treatment difference (-10.2 +/- 2.4 mmHg/P less than 0.001). There were no clinically or statistically significant changes in mean heart rate. Nineteen out of 20 patients in the amlodipine group compared to seven out of 18 patients on placebo, were assessed as improved by the investigator. Similarly 14 out of 19 patients receiving amlodipine were classified as responding to treatment (supine diastolic blood pressure less than 90 mmHg or reduction from baseline of greater than 10 mmHg after four weeks of double-blind therapy) in contrast to four out of 17 receiving placebo.(ABSTRACT TRUNCATED AT 250 WORDS)     

依那普利对原发性高血压糖耐量低减的影响

目的：了解依那普利对原发性高血压糖耐量低减的影响。方法：37例原发性高血压伴糖耐量低减的患者,于依那普利降压治疗3周后,测量治疗前后空腹血糖,血胰岛素,口服葡萄糖耐量试验（OGTT）2h血糖,血胰岛素,胰岛素敏感性指数（ISI）,糖化血红蛋白（HbA1c),总胆 醇和甘油三酯等指标。结果：治疗后OGTT2h血糖和空腹血胰岛素显著降低（P＜0．05）,ISI升高（P＜0．01）。结论：依那普利可改善原发性高血压病人的糖耐量低减。     

氯沙坦和依娜普利对高血压患者肾功能的影响

目的探讨血管紧张素Ⅱ受体拮抗剂(AIR)和血管紧张素转换酶掏剂(ACEI)对原发性高血压(EH)患者肾功能的影响.方法采用随机、单盲和平行对照方法,经1周药物冲洗期及2周安慰剂导入期后,60例EH患者(EH组)进行16周治疗期,每日1次口服氯沙坦50mg(n=30)或依那普利5mg(n=30),4周后加舒张压(DBP)≥90mm Hg(1mm Hg=0.133 kPa)则剂量加倍.治疗后测量血压、心率(HR)并记录症状、、体征并行24h动态血压监测(ABPM)1次.治疗前后分别测定血清肌酐(Cr)、尿素氮(BUN)、内生肌酐清除率(Ccr)和24h尿蛋白(UTP)、白蛋白(Alb),血尿(α1)及β2微球蛋白(α1-MG和β2-MG)的排泄率.20例健康体检者作为对照组.结果(1)两组药物均能明显降低血压(P＜0.05).(2)治疗前EH组患者Ccr显著低于对照组,(P＜0.01)血尿α1-MG和β2-MG及UTP、AlbEH组显著高于对照组,且上述指标改变程度与EH的病程相关.(3)治疗16周后,氯沙坦和依那普利均能显著降低UTP、Alb,血尿α1-MG和β2-MG,其中病程较长者,下降幅度较大.(4)咳嗽发生率氯沙坦组(6.7%)明显低于依那普利组(26.7%)(P＜0.01).结论(1)EH患者早期即有肾功能损害,且随病程延长损害加重.(2)氯沙坦可减轻和延缓高血压引起的肾功能损害,且病程较长者获益较大,其效果可能与依那普利相似.     

维尔亚和依那普利对原发性高血压患者心电图P波离散度的影响

目的 观察血管紧张素Ⅱ受体拮抗剂和血管紧张素转化酶抑制剂对原发性高血压（EH）患者心电图P波时限和离散度的影响。方法 EH患者68例,随机分为两组,维尔亚4 mg/d和依那普利10 mg/d,血压控制不良者可加用利尿剂和钙离子拮抗剂,共观察6个月。分别于用药前后测定12导联体表心电图中P波时限和P波离散度。结果 用药后两组均可使EH患者心电图P波时限和P波离散度减小,组间比较显示,维尔亚组的作用更优于依那普利组。结论 维尔亚对EH患者心电图P波时限和P波离散度的作用强于依那普利。     

依那普利对高血压病患者胰岛素抵抗影响的临床观察

测定５１例高血压病患者与２２例正常人空腹血糖（ＳＧ）、血胰岛素水平（ＩＳ）、Ｃ肽（ＣＰ），显示ＩＳ、ＩＳ／ＳＧ、胰岛素敏感指数（ＩＡＩ）、两组间有显著性差异（Ｐ＜０．０１），而ＣＰ／ＩＳ比值无统计学差异。高血压病患者用依那普利５～１０ｍｇ／ｄ，疗程４～１５个月（平均１１．２９±３．７１个月），后复查上述指标并与用药前进行对比分析。结果除血压明显下降外（Ｐ＜０．００１），空腹ＩＳ、ＩＳ／ＳＧ、ＩＡＩ亦均显著下降（Ｐ＜０．０１），而ＣＰ／ＩＳ比值治疗前后差异无显著性（Ｐ＞０．０５）。提示，原发性高血压病患者存在胰岛素抵抗现象，依那普利治疗除可有效降低血压外，尚有改善胰岛素抵抗的作用。     

Effect of enalapril on left ventricular mass and performance in essential hypertension

The effect of enalapril on left ventricular (LV) morphology and function was studied in 12 hypertensive patients. The subjects were evaluated after 2 weeks of placebo and after 4 months of treatment with enalapril (20 or 40 mg once daily), using M-mode digitized echocardiograms. The drug reduced arterial blood pressure in all patients. Systemic vascular resistance decreased significantly without changes in cardiac output and heart rate. No patient had significant side effects. After treatment LV mass decreased significantly (233 +/- 46 to 204 +/- 37 g, p less than 0.01); the reduction was due to a decrease in septal and posterior wall thickness, without changes in LV diameter. LV systolic function remained unchanged, whereas peak lengthening rate of LV dimension, an index of LV diastolic function, increased significantly (4.05 +/- 1.8 to 5.11 +/- 1.8 s-1, p less than 0.01). After treatment the basal inverse correlation between peak shortening rate and wall stress did not change, the inverse correlation between peak lengthening rate and wall stress became closer and the basal inverse correlation between peak lengthening rate and LV mass disappeared. In conclusion, antihypertensive treatment with enalapril led to a significant regression of LV hypertrophy associated with improvement in LV diastolic performance and no deterioration of LV systolic function.     

Clinical experience with labetalol and enalapril in combination in patients with severe essential and renovascular hypertension

Severe hypertension may be a difficult management issue, and it often requires therapy with multiple drugs at frequent dosing intervals. We report on the antihypertensive effects of the alpha-beta adrenergic blocking agent, labetalol, in combination with enalapril, a long-acting angiotensin-converting enzyme inhibitor, administered to 14 patients with severe hypertension (nine of whom had nephrosclerosis or renal artery stenosis) on other antihypertensive drug therapies. Blood pressure (BP), heart rate (HR), hematologic and blood chemistry values, and adverse side effects were monitored at 24 hours, 1 week, and 4 weeks of therapy. Rapid titration of the drugs was performed in the hospital in 10 patients; four were managed closely as outpatients. Following one month of combination therapy blood pressure decreased from 212 +/- 31/120 +/- 16 mm Hg at baseline to 155 +/- 19/86 +/- 12 mm Hg, and heart rate declined from 86 +/- 18 bpm to 70 +/- 16 bpm. Ten of the 14 patients (71%) maintained good BP control (BP less than 140/90 mm Hg) with no additional treatment. Serum potassium, creatinine, blood urea nitrogen concentrations, and hematologic parameters did not significantly change in 13 of 14 patients. Three patients developed symptomatic postural hypotension; in one patient this side effect resulted in discontinuation from the study. These data suggest that combination therapy with labetalol and enalapril is effective in lowering BP in patients with severe essential or renovascular hypertension. An additional advantage of this regimen is the twice-daily dosing interval, which may promote better long-term compliance.     

The comparison of hypotensive efficiency and tolerability of amlodipine and enalapril in patients with essential hypertension

In this multicentre, double-blind trial in 176 patients with mild or moderate essential hypertension were randomized to amlodipine or enalapril monotherapy after 2-week period of placebo. Doses of amlodipine (2.5-10 mg once daily) and enalapril (5-20 mg once daily) were titrated to achieve office blood pressure below 140/90 mm Hg during 8 weeks of therapy. Both drugs were similarly effective in lowering blood pressure and goal blood pressure was achieved in 72.4% patients treated with amlodipine and 67.4% with enalapril. Also, degree of reduction of blood pressure was similar in both groups. Compared to initial values: systolic/diastolic blood pressure decreased by 23.5/14.9 mm Hg in amlodipine group and 23.2/14.0 mm Hg in subjects receiving enalapril. However, adverse effects, especially dry cough were more frequent in enalapril-treated patients. Both amlodipine and enalapril provide significant blood pressure reduction in stage I-II hypertension. Tolerance of short-term therapy was good in both groups however number of adverse events was significantly lower in amlodipine-treated patients.     

Serum concentration and effects of a single dose of enalapril maleate in patients with essential hypertension

The antihypertensive effect of a non-sulfhydryl, long acting ACE (angiotensin converting enzyme) inhibitor, MK-421, was evaluated by administering a single dose of 10 mg to 13 patients with mild to moderate essential hypertension. The pharmacokinetic profile of MK-421 and its potent active metabolite, MK-422, was also assessed, together with the effect on the various components of the renin-angiotensin system. A single dose of MK-421 produced a significant fall in MBP from 2 to 24 hours post-drug. As could be expected, plasma ACE activity was suppressed up to 24 hours after MK-421. The half-life of MK-422, Cmax and [AUC]24(0) of MK-421 and MK-422 were measured. No significant change in plasma bradykinin or urinary excretion rate of kallikrein was observed, whereas a slight increase was observed in the urinary excretion rate of kinins after MK-421 in 8 patients. Significant correlations were observed between pretreatment PRA levels and the maximum fall in MBP.     

The effect of treatment with enalapril versus losartan on levels of insulin resistance in patients with essential hypertension

Insulin resistance and hyperinsulinaemia are presumed to participate in the pathogenesis of essential hypertension (EH). Insulin resistance is characterised by an impaired insulin-mediated glucose uptake. Participation of the renin-angiotensin system in the development of hyperinsulinaemia in EH patients has not been unanimously proven. The present study aimed to asses the influence of antihypertensive therapy with angiotensin converting enzyme inhibitor (ACEI, enalapril = 10 mg/day) (9 male patients) or angiotensin II AT-1 receptor blocker (A II RB = losartan 50 mg/day) (9 male patients) respectively on insulin sensitivity in patients with EH. 3-hours euglycaemic clamp test with constant infusion of insulin (50 mU/m2/min) was performed twice: before and after 8 weeks of therapy with ACEI or A II RB respectively. The control group (CG) consisted of 12 healthy males (clamp test was performed once). Serum insulin concentration (I) was estimated by radioimmunoassay. Glucose disposal rate (M-value = mg/kg/min) and tissue insulin sensitivity (M/I value = mg/kg/min per mU/l) were calculated in subjects of the CG and in patients with EH before and after antihypertensive therapy with ACEI or A II RB, respectively. In CG the M-value (7.38 +/- 0.13) and tissue insulin sensitivity (M/I = = 6.76 +/- 0.19) were significantly higher than in EH before treatment with ACEI (M-value = 5.44 +/- 0.16; M/I = = 4.57 +/- 0.18) or A II RB (M-value = 5.75 +/- 0.21; M/I = 4.77 +/- 0.31), respectively. ACEI therapy was followed by a significant increase of both M (6.82 +/- 0.25) and M/I (5.68 +/- 0.25) values. In contrast to ACEI, treatment with A II RB did not influence neither M (5.75 +/- 0.21) nor M/I (4.79 +/- 0.21) values respectively. In contrast to A II RB, ACEI shows a beneficial effect on insulin sensitivity in EH patients. This effect does not seem to be mediated by an influence on the AT-1 receptor.     

Vasodilator effects of enalapril in patients with arterial hypertension

Although it has been recognized that enalapril lowers blood pressure by reducing the total peripheral vascular resistance, its direct effect on blood vessels is largely unknown. Little information is available about the influence of enalapril on the different vascular regions. Ten patients with moderate essential hypertension were treated with enalapril 20 mg daily in a double-blind, placebo controlled cross-over study for six weeks during each period. Blood pressure and heart rate were measured in supine, sitting and standing position. Venous capacity was derived from pressure volume curves plotted simultaneously at forearm and calf. Arterial blood flow at rest and during reactive hyperemia was measured at calf and finger by plethysmography. Enalapril increases venous capacity in upper and lower limbs in patients with moderate essential hypertension. Also, there is vasodilation of calf and finger arteries both at rest and during reactive hyperemia. Finger and calf arteries contribute to the decrease of the total peripheral vascular resistance during treatment with enalapril; thus, ACE inhibition is capable of correcting the increased peripheral resistance which often is the main cause of arterial hypertension.     

依那普利对老年高血压病患者血管活性物质和细胞离子转运的影响

目的 探讨依那普利对老年原发性高血压（EH）患者血管活性物质和细胞离子转运的影响。方法 测定23 老年EH患者和21名健康老年人血浆内皮素、血管紧张素Ⅱ、去甲肾上腺素和内源必类洋地黄物质及淋巴细胞Na^ 、Ca^2 转运,并观察依那普利治疗6个月后各指标的改变。结果 老年EH患者血浆四种升压物质水平升高,细胞钠泵和钼泵活性、K^ 浓度降低,Na^ 和Ca^2 浓度增高;四种升压物质分别与离子泵、Na^ 和Ca^2 相关,依那普利治疗后各指标改善。结论 老年EH与多种血管活性物质产生增加,细胞Na^ 、Ca^2 转运障碍及其相互作用有关,依那普利长期治疗能改善其异常的病理生理。     

脉压在老年高血压病患者中的作用

目的：探讨老年高血压病患脉压（PP）与左室重量指数（LVMI）和外周血单个核细胞端粒酶活性（TMa)变化的关系。方法：用血压计,超声心动图和端粒酶PCR－ELISA方法检测61例老年高血压病患和20例血压正常PP＜60mmHg的,PP,LVM和TMa。结果：高血压≥60mmHg组TMa比血压正常组的高（P＜0．05）,高血压PP≥60mmHg组与高血压PP＜60mmHg组和血压正常组比LVMI最高（P均＜0．05）,结论：脉压增大促进老年高血压性左室肥厚和外周血单个核细胞TMa。     

Antihypertensive effect of enalapril in essential hypertension: role of prostacyclin

The effects of enalapril alone and in combination with the cyclooxygenase inhibitors sulindac and indomethacin on blood pressure (BP), plasma aldosterone, renin activity and converting enzyme activity were evaluated in 29 patients with mild to moderate essential hypertension, 26 of whom had low plasma renin activity. Patients were randomly assigned to one of three treatment groups. All patients underwent a 4-week placebo phase (phase I), then received enalapril (20 mg BID) for 4 weeks (phase II). In phase III, group I (n = 10) continued on enalapril alone; group II (n = 9) received sulindac 200 mg BID plus enalapril, and group III (n = 10) received indomethacin 50 mg BID plus enalapril, all for 4 weeks. Enalapril lowered BP significantly (mean supine BP 149/100 in phase I vs. 134/90 in phase II, p less than 0.05) without inhibiting aldosterone production. The BP effect was not blunted by concomitant administration of sulindac or indomethacin. Enalapril lowered converting enzyme activity to 25% to 30% of baseline and tended to increase renin activity. In the 10 patients who received indomethacin (group III), the effects of enalapril alone and enalapril plus indomethacin on urinary excretion of 6-keto prostaglandin F1 alpha (PGF1 alpha), a stable metabolite of prostacyclin (PGI2), were examined. Enalapril increased urinary 6-keto PGF1 alpha in group III from 118 +/- 23 to 194 +/- 38 ng/g creatinine (p less than 0.05), while addition of indomethacin reduced 6-keto PGF1 alpha to basal levels (138 +/- 26 ng/g creatinine).(ABSTRACT TRUNCATED AT 250 WORDS)     

A parallel study of enalapril and captopril and 1 year of experience with enalapril treatment in moderate-to-severe essential hypertension

Angiotensin converting enzyme (ACE) inhibitors, enalapril (5 to 20 mg twice daily) or captopril (25 to 100 mg thrice daily) and matching ACE inhibitor placebos were given to 32 moderate-to-severe essential hypertension patients who were already on 50 mg hydrochlorothiazide daily. Alpha-methyldopa (250 to 500 mg twice daily) was given to 16 patients following 6 weeks of ACE inhibitor therapy. Both enalapril and captopril significantly (p less than 0.05) lowered the supine and upright blood pressures (BPs) (acutely and long-term) without significant reflex heart rate changes. The BPs of enalapril patients were, however, significantly lower (supine diastolic p less than 0.03, supine systolic p less than 0.05, and upright diastolic p less than 0.04) than those of captopril patients when compared by repeated measures of analysis of variance. Eleven enalapril patients have been followed for 1 year with continued BP control. Skin rash occurred in one captopril patient and reversible renal insufficiency developed in two enalapril patients during the first 16 weeks. It is concluded that (although both ACE inhibitors lowered BP, enalapril was more effective than captopril and twice-daily enalapril was well tolerated during 52 weeks of treatment.     

Effect of indomethacin on blood pressure in elderly people with essential hypertension well controlled on amlodipine or enalapril

Arthritis and hypertension are frequent comorbidities in the elderly hypertensive population. Nonsteroidal anti-inflammatory drugs are often used to relieve pain in arthritic patients but a side effect is sodium retention and consequent elevation of blood pressure (BP). The effect of dihydropyridine calcium blocking drugs is relatively independent of sodium intake, whereas the angiotensin-converting enzyme (ACE) inhibitors' effects can be blunted by a high-sodium diet. This study compared the effects of indomethacin with placebo in elderly patients with essential hypertension who had been controlled with amlodipine or enalapril. Indomethacin 50 mg twice daily or placebo was administered for 3 weeks in a double-blind crossover study to patients controlled with amlodipine or enalapril. The response was assessed by ambulatory BP measurement. Indomethacin raised BP and lowered pulse rates in patients taking enalapril but had little effect in patients receiving amlodipine. The difference caused by indomethacin between the two groups was 10.1/4.9 mm Hg increase in BP and a 5.6 beats/min fall in pulse in people taking enalapril. Addition of indomethacin to patients taking either drug caused a rise in weight and a fall in plasma renin. It is postulated that the effect is due to inhibition of prostaglandin synthesis, which causes sodium retention. In patients taking amlodipine, the fall in plasma renin ameliorates the effect of sodium retention on BP. In patients taking enalapril, plasma renin falls but this is not translated into an effect because of the blockage of converting enzyme. Thus, the full effect of sodium retention on BP is expressed. In patients treated with indomethacin, fewer patients may respond to ACE inhibitors. However, the major problem is the patient who intermittently takes indomethacin or other nonsteroidal anti-inflammatory drugs, which, if a person is treated by an ACE inhibitor causes BP to go out of control. In such patients amlodipine would appear to be a preferred choice to enalapril.     

Metabolic effects of enalapril in the treatment of essential hypertension.

In an open two-month study with an initial placebo period, the effect of enalapril on glucose tolerance, insulin (IRI) sensitivity and lipid profile was evaluated in 20 patients with mild to moderate essential hypertension. The following results were obtained: 1. Enalapril produced a favourable effect of blood pressure both in monotherapy and if combined with a diuretic. 2. Therapy did not lead to significant differences in blood glucose, IRI or IRI/glucose increase at 1 or 2 hours of oral glucose tolerance test either in patients with monotherapy or combination therapy, and with normal or disturbed glucose tolerance, respectively. 3. Serum lipids (total and HDL-cholesterol and triglycerides) did not change significantly in any group of patients.