硝苯啶与普萘洛尔治疗原发性高血压118例

原发性高血压118例(男72例,女46例;年龄54±12a;病程12±4a)采用硝苯啶(5-30mg/d,po)与普萘洛尔(5-30mg/d,po)合用治疗4a以上者,有效率100％,平均降压5.6/2.1kPa,脑卒中并发症减少,副反应轻微。复降片对照组80例(男49例,女31例;年龄52±13a;病程8±6a)采用复降片2-10片/d,po,治疗4a以上者,有效率64％,平均降压2.1/1.4kPa,与前者比较,P<0.01。     

Plasma concentrations of propranolol in patients with essential hypertension

Summary Sixteen patients with essential hypertension were treated with propranolol 160 to 640 mg daily for three months. Significant decreases both in recumbent and standing blood pressure were observed after three days treatment and subsequently. Reduction of blood pressure was more pronounced when the dose of propranolol was increased. However, neither the mean dose nor the plasma concentration of propranolol could be correlated with the mean decrease in blood pressure. There was great interindividual variation in the plasma concentrations of propranolol produced by the same daily dose. The initial stimulation of plasma renin activity and the therapeutic response to propranolol could not be correlated.     

The effects of oxprenolol on ambulatory intra-arterial blood pressure in essential hypertension

Summary Continuous intra-arterial blood pressure recording using the Oxford technique has been used to study the antihypertensive effects of oxprenolol taken three times daily in fully ambulatory patients with essential hypertension, outside hospital. During the first 24 h of treatment there was a reduction in daytime heart rate and a small reduction in daytime blood pressure. After 10 weeks treatment there was a more substantial fall in daytime blood pressure from the hour of waking, but no effect on sleeping nighttime blood pressure or heart rate. Twenty-four hour variation, as assessed by the amplitude of a fitted regression curve, showed a reduction in heart rate but not blood pressure variation. In 4 patients restudied after 11 weeks treatment with oxprenolol (tid) and cyclopenthiazide at 9 a.m. there was some evidence of an antihypertensive effect occuring during both the daytime and nighttime.     

TJ0711对自发性高血压和哇巴因-高血压麻醉大鼠的急性降压

目的:观察新型肾上腺素α,β受体双重阻断剂TJ0711静脉注射对自发性高血压大鼠(SHR)和哇巴因-高血压大鼠(OHR)2种模型的急性降压作用。方法:制备OHR模型:SD大鼠连续8周腹腔注射30 μg·kg^-1·d^-1哇巴因,将收缩压>21.3 kPa(1 kPa≈7.5 mmHg)者随机分为生理盐水(N.S)组、TJ0711 0.3,0.9,2.7 mg·kg^-1剂量组、阳性对照卡维地洛1 mg·kg^-1组(n=12);购得的SHR分组方法同OHR。用10%乌拉坦(1.3 g·kg^-1,i.p)麻醉,仰位固定,分离一侧颈总动脉插管连接多通道生理记录仪测血压和心率,颈外静脉插管给药。观察给药前后大鼠收缩压、舒张压、心率的变化,分析TJ0711静注降压作用规律。结果:TJ0711静注给药后2~15 min即达到最大降压水平,降压作用维持25~75 min。对SHR和OHR两种高血压模型收缩压与舒张压下降趋势一致,但对SHR收缩压、舒张压最大降压幅度高于OHR。结论:TJ0711静脉注射能快速、短效降低SHR和OHR两高血压模型大鼠的血压同时使心率适当减慢,具有良好的急性降压特点。     

Evaluation of two oxprenolol oral osmotic (OROS) delivery systems in patients with essential hypertension

Summary The effects of two oxprenolol oral osmotic (OROS) delivery systems on heart rate and blood pressure before and during recovery from exercise at a predetermined load were examined in twelve patients with hypertension previously responding to beta-blocker monotherapy. Haemodynamic responses were attenuated during the 24 h after single and repeated (15 days') once daily administrations of 10/170 and 16/260 oxprenolol OROS.At 24 h after repeated doses, compared to placebo there were significant reductions in resting blood pressure and in heart rate immediately following exercise. Attenuation of heart rate after exercise was dose related but differences between the systems with respect to resting heart rate and blood pressure were inconsistent. Antihypertensive responses after repeated doses were greater than those after single doses.However, reductions in resting and exercise heart rates were consistently less on chronic therapy. This may reflect enhanced expression of the partial agonist activity of oxprenolol due to altered receptor sensitivity after prolonged beta-blockade.The plasma oxprenolol profiles after both systems indicated slow absorption and substantial concentrations were apparent 24 h after drug administration.These observations suggest that both oxprenolol OROS systems display sustained drug release and on once daily dosing provide 24 h beta-blockade and control of blood pressure at rest and following exercise.     

三物降压汤、通经调脏法推拿联合对眩晕合并高血压患者控压效果的影响

目的 探析三物降压汤、通经调脏法推拿联合对眩晕合并高血压患者控压效果的影响.方法 选取眩晕合并高血压患者300例作为研究对象,按照随机数字表进行编号,奇数号纳入观察组(n=153)、偶数号纳入对照组(n=147).对照组应用苯磺酸氨氯地平片和(或)厄贝沙坦片进行治疗,观察组在对照组基础上联合三物降压汤、通经调脏法推拿治疗.比较两组治疗前后收缩压(SBP)、舒张压(DBP)、血浆内皮素(ET)、一氧化氮(NO)差异,记录眩晕证候总有效率,另分组记录两组生活质量、不良反应发生率.结果 观察组眩晕证候总有效为91.5％,高于对照组82.3％,差异有统计学意义(P<0.05).两组治疗前SBP、DBP、ET、NO、生活质量各项评分的差异无统计学意义(P>0.05);治疗后两组SBP、DBP、ET、生活质量各项评分均降低、NO升高(P<0.05),观察组治疗后的SBP、DBP、ET分别降低至(118.7±7.9)mmHg、(78.3±5.2)mmHg、(50.4±6.1)pg·L-1,低于对照组(P<0.05),生活质量各项评分也低于对照组(P<0.05);NO为(171.4±16.0)μmol·L-1,高于对照组(P<0.05).结论 三物降压汤可有效清肝降火、降脂降压,通经调脏法推拿则可通经调脏改善血管内皮活性,调节ET与NO的合成与释放,控压效果良好,眩晕症状改善明显.     

高迁移率族蛋白1基因多态性与中国南方农村常用高血压药物疗效的关系

目的：研究参与AGER氧化损伤通路的高迁移率族蛋白1（HMGBI）基因的遗传变异对于高血压药物效果的影响。方法：采用流行病学现况调查方法,对服用复方利血平、珍菊降压片和降压片的高血压患者（780例）进行流行病学和临床生化指标资料的收集。位点选择采用连锁不平衡分析和生物信息学的功能预测相结合的方法,选择HMGBl基因的3个标签单核苷酸多态性（tagSNPs）与服用不同降压药物后人群血压水平的关系。结果：服用复方利血平的高血压病人中,rs1412125位点与舒张压水平呈线性负相关,携带CC等位基因的病人舒张压水平明显低于TT和TC等位基因,调整混杂因素后P值为0．040。服用珍菊降压片的女性高血压病人中,rs1045411的G到A的突变和rs2249825的C到G的突变,收缩压都有明显的下降,校正混杂因素后P值分别为0．044、0．043。服用降压片的≥55岁人群中,rs2249825位点不同基因型之间的收缩压的差异,校正协变量后仍有统计学意义（P=0．048）。结论：HMGBI基因多态性可能影响复方利血平、珍菊降压片和降压片的降压效果。     

硝苯地平控释片与普通片治疗老年高血压病比较

目的 比较硝苯地平控释片与普通片对老年高血压患者的降压疗效。方法 采用随机、单盲的方法，对８４例老年高血压患者进行２４ｈ动态血压监测，比较其疗效及副反应。结果 两药均能显著降低老年高血压患者的偶测血压及２４ｈ平均血压（Ｐ〈０．０１）。两药在降低偶测压缩压、２４ｈ平均收缩压及白天平均血压幅度方面差异无显著性（Ｐ〉０．０５），硝苯地平控释片能明显降低患者的偶测舒张压（Ｐ〈０．０５）、２４ｈ平均舒张压（     

硝苯地平对原发性高血压患者内皮功能和左心室肥厚的影响

目的探讨硝苯地平对原发性高血压患者内皮功能和左心室肥厚的影响。方法选择未经治疗的伴左心室肥厚的原发性高血压患者84例随机分为2组,治疗组42例口服硝苯地平30mg每天1次,对照组42例口服氢氯噻嗪（HCT）25mg,每天2次,疗程为1年。治疗前后检测2组患者内皮功能和左心室肥厚指标。结果治疗组患者治疗后一氧化氮（NO）和前列环素（PGI2）水平较治疗前长升高（P〈0.05）,内皮素（ET）和血栓素A2（TXA2）较治疗前降低（P〈0.05）,而对照组上述指标无明显变化（P〉0.05）。2组治疗后上述指标差异有统计学意义（P〈0.05）。治疗组患者左心室肥厚均明显逆转（P〈0.05）,对照组患者治疗前后左心室肥厚指标无显著差别（P〉0.05）。结论硝苯地平能改善原发性高血压患者的内皮功能,逆转左心室肥厚,是原发性高血压治疗的理想药物。     

Acute and chronic effects of nifedipine in arterial hypertension

Summary Sublingual administration of nifedipine 10 mg to 11 patients and 20 mg to 6 patients with arterial hypertension caused a rapid and significant decrease in blood pressure in both groups. The average maximal reductions in the two groups were 21/16 mm Hg and 27/21 mm Hg. A concomitant rise in heart rate was found. Forearm blood flow showed a significant increase and the calculated vascular resistance a significant decrease 15–60 min after administration of both the 10 mg and the 20 mg doses. There was a negative correlation between basal vascular resistance and the maximal change of this parameter (r=–0.72, p<0.01). Plasma concentrations of nifedipine showed considerable individual variation, with slow absorption in some patients, which indicated failure of sublingual absorption in them. The difference between the mean plasma concentration in the two dose groups was statistically significant after 45 min. A negative correlation was present between the plasma concentration of nifedipine and the observed change in calculated vascular resistance (r=–0.74 at t=30 min). Treatment of 10 hypertensive patients with nifedipine 30–60 mg daily for 6 weeks reduced mean blood pressure from 175/115 mm Hg to 151/96 mm Hg (p<0.001). Heart rate and forearm blood flow rose, whereas the forearm vascular resistance showed a significant decrease. Side effects of a sensation of heat and reddening of face were noted in some patients. It is suggested that nifedipine may be useful both in the acute and chronic treatment of arterial hypertension.     

Magnesium depletion in patients on long-term chlorthalidone therapy for essential hypertension

Summary Sixty patients were treated for 1 year for essential uncomplicated hypertension, 30 with beta-blockers alone (BB) and 30 with BB and chlorthalidone (CTD). BB did not affect serum K⁺ or Mg⁺⁺. In the BB-group there was a statistically significant trend towards retention of Mg⁺⁺ in a loading test, but the effect was clinically marginal. BB + CTD reduced serum K⁺ and Mg⁺⁺ and caused significant Mg⁺⁺ depletion, as shown by the Mg⁺⁺ loading test. All the effects were highly significant and were clinically important. The metabolic perturbations due to CTD are potentially dangerous and make this drug unattractive as first choice treatment for hypertension.     

Haemodynamic effects and plasma concentrations of labetalol during long-term treatment of essential hypertension

1 Fifteen men with untreated essential hypertension in WHO stage 1 were studied on an outpatient basis to evaluate the haemodynamic long-term effect of a new α- and β-adrenergic receptor blocker, labetalol.

2 Oxygen consumption, heart rate, cardiac output (Cardiogreen) and intraarterial brachial pressure were recorded at rest in a supine and sitting position, and during steady state work at 300, 600 and 900 kpm/min.

3 The subjects were treated with labetalol (dose 200-800 mg/day) as the sole drug for 1 year. The haemodynamic study was then repeated and the concentration of labetalol in plasma 2-2.5 h after the morning dose was measured.

4 Mean arterial blood pressure was reduced approximately 23% at rest and 21% during exercise. The heart rate was decreased 15% at rest and 16% during exercise. There was a compensatory increase in the stroke volume and consequently the cardiac index was reduced less than the heart rate, 7% at rest supine and 10% during exercise. There was a significant decrease in total peripheral resistance at rest supine (16%) and during exercise (12%).

5 No serious side-effects were seen, but two subjects almost syncopated in the sitting position after the 900 kpm/min work load at the restudy.

6 There was no correlation between the plasma concentration and the effect of labetalol.

7 The haemodynamic changes differ from those seen after long-term therapy with drugs possessing only β-adrenoceptor blocking properties, and agree well with what should be expected with a drug which possesses both α- and β-adrenoceptor blocking properties.

     

小檗碱与硝苯地平治疗原发性高血压的比较

原发性高血压７８例，采用小檗碱治疗３８例（男性３６例，女性２例；年龄６４±ｓ５ａ）；剂量０．３－０．６ｇ，ｔｉｄ或ｑｉｄ。另外４０例采用硝苯地平治疗（男性３８例，女性２例；年龄６５±５ａ），剂量１０－２０ｍｇ，ｔｉｄ或ｑｉｄ。２组均以４ｗｋ为一个疗程。结果提示小檗碱对高血压患者的舒张压有降压效果，但疗效远不及常用量之硝苯地平（３４％ｖｓ９０％）（Ｐ＜０．０１），惟不良反应轻微。     

Effect of nifedipine monotherapy on platelet aggregation in patients with untreated essential hypertension

Summary The effect of 6 weeks of nifedipine 30–60 mg/d on platelet aggregation and lipid parameters has been studied.A diminution in ADP-, adrenaline- and collagen-induced aggregation was observed. In the case of adrenaline-and collagen-stimulated aggregation the decrease was statistically significant. It was found that platelets which aggregated markedly during the placebo treatment were most strongly inhibited by nifedipine. The changes in lipid parameters were not significantly correlated with changes in aggregation.This report is a part of a project realized within the frames of the government programme of studies of the side-effects of hypotensive drugs given for 1 year.     

Prazosin partly blocks clonidine-induced hypotension in patients with essential hypertension

Summary Prazosin has been reported to reduce the hypotensive and/or bradycardic effect of clonidine in various animal models. Investigations in humans have given conflicting conclusions about the effectiveness of the combination of clonidine and prazosin. In patients with essential hypertension prazosin significantly reduced the hypotensive effect of intravenous clonidine, but it failed to affect the clonidine-induced bradycardia. This finding means that the combination of prazosin and clonidine is inappropriate in antihypertensive therapy.     

拉西地平对高血压病患者肾脏的作用

目的:评价拉西地平对原发性高血压患者肾脏的作用.方法:18例原发性高血压病住院患者(男16例,女2例),血压(23±2/14±1)kPa[(169±13/108±9)mmHg],分别在停降压药1～2wk.低钠饮食(20mmol/d)×5d,高钠饮食(26mmol/d)×5d及服用拉西地平(4～6mg/d)×4wk,测定肾小球滤过率(GFR内生肌酐清除率),同位素肾血流量(RPF),尿微量白蛋白排泄率(UMAE)及视黄醛结合蛋白排泄率(URE).结果:低钠比高钠状态UMAE显著下降(P<0.01),服拉西地平后GFR、RPF均有增加,但不显著.在GFR由(127±43)上升到(143±36)ml/min时UMAE明显减少(26.2mg/24h到15.0mg/24h,P<0.05),结论:拉西地平不降低原发性高血压病病人的肾功能,并能减少UMAE;减少UMAE可能与肾血流动力学改变无关.     

Effects of treatment with nifedipine and metoprolol in essential hypertension

Summary In a double-blind trial 26 patients with essential hypertension were treated with nifedipine or placebo for 8 weeks, following a 4-week run-in place-bo period in all patients. The daily dosage of nifedipine during this phase was 10mg 3 times daily. Metoprolol was then added to the therapeutic regimen of both groups for a further 12 weeks. Both nifedipine and metoprolol used as mono-therapy caused statistically significant reductions of arterial pressure. The addition of metoprolol to nifedipine tended to reduce blood pressure further, but blood pressures were not significantly lower than during nifedipine mono-therapy. Side-effects were few and only two patients had to be withdrawn during active therapy, one for headaches during nifedipine therapy, and another for asthma during metoprolol treatment. Combined therapy with a beta-adrenoceptor blocking agent, such as metoprolol, and a calcium antagonist with vasodilating properties, such as nifedipine, offers a theoretically interesting approach in the treatment of hypertension, even though the practical outcome in the present study probably suffered from an inadequate dose of nifedipine during the period of combined therapy.     

Acute haemodynamic response in relation to plasma vardenafil concentrations in patients with pulmonary hypertension

AIMS

To evaluate the acute haemodynamic effects of a single oral dose of vardenafil and to study the drug concentration in relation to haemodynamic effects in patients with pulmonary hypertension (PH).

METHODS

Sixteen patients with PH (aged 29–85\ years), received one single oral dose of vardenafil (5, 10 or 20 mg). The haemodynamic effect was assessed over a 60 min period. Vardenafil plasma concentrations were measured after 15, 30, 45 and 60 min using liquid chromatography–tandem mass spectrometry.

RESULTS

At 60 min a reduction in mPAP with a median % decrease of −20.3% (range −48.3 to 3.0; P < 0.001) and an increase in cardiac output and the cardiac index with a median % change of 10.6% (range −25.0 to 88.1; P = 0.015) and 12.1% (range −24.0 to 94.4; P = 0.01) respectively was observed. The pulmonary vascular resistance (PVR) was reduced with a median % decrease of −28.9% (range −61.5 to −5.9; P < 0.001), and pulmonary selectivity was reflected by a median percent reduction of −16.9% (range −49.0 to 16.5; P = 0.002; n = 14) in the PVR/systemic vascular resistance ratio. There was a correlation between the plasma concentrations of vardenafil and change in mPAP (r = −0.579, P = 0.019) and between vardenafil concentrations and change in PVR (r = −0.662, P = 0.005).

CONCLUSIONS

Vardenafil causes rapid changes in cardiopulmonary haemodynamics and there is a correlation between plasma vardenafil drug concentration and the acute changes in mPAP as well as PVR in patients with PH.     

临床中西降压药物的成本效果分析综合评价

目的观察4种降压药的降压效果、症状改善、不良反应及对高血压病患者生活质量(QOL)的影响,并对4种药物作成本-效果分析(CEA).方法将292例轻、中度高血压病患者,随机分成4组,疗程均为6周.QOL测定采用SF-36量表,CEA综合评价采用效果决策模式.结果按综合评价得分高低依次为:吲达帕胺(3.65)、珍菊降压片(3.30)、苯磺酸氨氯地平(2.90)、盐酸苯那普利(2.35).结论4种降压药不仅有良好的降压效果,改善症状积分、且不良反应也较少;评价和选择降压药物,应结合QOL测评;CEA综合评价表明珍菊降压片列第2位,提示应重视中西结合复合降压制剂的应用.     

缬沙坦长期治疗原发性高血压病人的安全性和疗效

目的 :评估缬沙坦长期治疗原发性高血压的安全性与疗效。方法 :门诊轻、中度高血压的病人3 2例 (男性 2 3例 ,女性 9例 ,年龄 5 1a±s 9a) ,服用缬沙坦 80mg·d-1,wk 4后血压控制不满意者加量至 1 60mg·d-1,共治疗 2 4wk。结果 :舒张压下降程度在治疗后wk 4,8,1 6,2 4末分别为 :1 .6kPa±0 .9kPa,2 .0kPa± 0 .8kPa,2 .1kPa± 1 .0kPa,1 .8kPa± 0 .8kPa,较治疗前差异均有非常显著意义 (P<0 .0 1 )。wk 4,2 4治疗有效率分别为 78%与 75% (P >0 .0 5 )。未见干咳发生 ,不良反应少 ,耐受性良好。结论 :缬沙坦长期治疗轻、中度原发性高血压安全有效