Randomised controlled comparative study of methyldopa and oxprenolol in treatment of hypertension in pregnancy.

One hundred pregnant women with hypertension (defined as diastolic blood pressure at or above 95 mm Hg) were allocated at random to treatment with methyldopa or oxprenolol and were compared with nonhypertensive controls matched according to parity and gestation at delivery. The patients were also stratified into those entering the study early (before 32 weeks'' gestation) and those entering late (after 32 weeks'' gestation). Although there were no differences in diastolic blood pressure between the hypertensive groups before or during treatment, in the early entry group the systolic blood pressure at entry of those allocated to oxprenolol was significantly higher than that of those receiving methyldopa; this difference remained throughout the treatment period. Also in the early entry group further increments of drug treatment were required to control blood pressure of patients receiving oxprenolol than in those receiving methyldopa. The eventual fetal outcome for all patients treated with methyldopa was the same as that for those treated with oxprenolol; birth weight, placental weight, head circumference, and Apgar score were not significantly different and there were no stillbirths in either group.     

Treatment of Hypertension with Propranolol

When used in the treatment of hypertension propranolol is at least of similar potency to bethanidine, guanethidine, and methyldopa. Propranolol does not produce postural or exercise hypotension and it seems that it is often more acceptable to patients than conventional drugs. It usually produces the best control of the supine blood pressure.A series of 109 hypertensive patients was treated with propranolol; in nine the drug was withdrawn. In 92 of the patients a supine or standing blood pressure of 100 mm. Hg or less was achieved. Eighty of the patients had previously been treated with other potent drugs, and close comparisons and prolonged follow-up in 17 patients showed that diastolic pressures of 100 mm. Hg or less were achieved in more patients after propranolol than with guanethidine, bethanidine, or methyldopa.Sensitivity to propranolol varies widely, and dosage should be increased gradually. The hypotensive effect often takes six to eight weeks to reach its maximum. Propranolol reduces cardiac output but may also act by reducing the cardiac component of pressor stimuli; as a result the baroreceptors gradually regulate the blood pressure at a lower level. It is contraindicated in patients with obstructive airways disease or in uncompensated heart failure.     

A Within-patient Comparison of Debrisoquine and Methyldopa in Hypertension

In a titrated dose cross-over trial of debrisoquine and methyldopa in 38 hypertensive patients neither drug was superior in lowering supine or standing diastolic pressure with a minimum of side effects. Methyldopa caused significantly greater reduction of supine (P<0·001) and standing (P<0·02) systolic pressure but caused intolerable side effects in two patients. Tiredness was the most characteristic and troublesome side effect with methyldopa and postural hypotension was prominent in patients while on debrisoquine.     

Effect of methyldopa treatment on cardiac function and myocardial blood flow in mongrel dogs.

Administration of methyldopa (100 mg/kg, orally twice daily for a period of 3 days) to mongrel dogs produced significant reductions in blood pressure and heart rate. The hypotensive effect of the drug was due to a reduction in peripheral resistance. Methyldopa treatment also produced a significant decrease in coronary vascular resistance. Studies on the left ventricular function indicated that treatment with methyldopa does not compromise the ability of the myocardium to respond to an increased work load. Thus, the beneficial effect of this agent on the myocardial circulation, together with its lack of any detrimental effect on the cardiac function suggest that methyldopa may be an effective agent for the control of hypertension.     

Randomised comparison of methyldopa and oxprenolol for treatment of hypertension in pregnancy.

Fifty-three pregnant women with moderately severe hypertension were randomly allocated to treatment with methyldopa or oxprenolol. There were no significant differences between the groups in age, height, weight, parity, or stage of gestation at the start of treatment. The outcome of pregnancy was better in the group treated with oxprenolol, with greater maternal plasma volume expansion and placental and fetal growth. No intrauterine deaths occurred in either group, and antepartum fetal distress, detected by oxytocin challenge testing, was evident in only one patient, who received methyldopa. This infant, and one other in the methyldopa group, died in the neonatal period. No neonatal deaths occurred in the oxprenolol-treated group. Even in this small number of patients these results were considerably better than those in untreated women with hypertension of similar severity. Apgar scores in both groups were equivalent at birth, while blood sugar concentrations were higher in the oxprenolol group. Oxprenolol appears to be safe and effective in controlling hypertension during pregnancy. There was no evidence of harmful effects on the fetus, and oxprenolol may offer a selective advantage over methyldopa for fetal growth and wellbeing in utero.     

Methyldopa and propranolol or practolol in moderate hypertension.

The effect of a low dose of methyldopa combined with (a) a non-selective and (b) a selective beta-adrenoceptor antagonist was studied in a double-blind crossover trial in 24 carefully selected patients with moderate hypertension (mean initial lying blood pressure 189/117 mm Hg). Each patient received methyldopa 750 mg/day, propranolol 240 mg/day, practolol 600 mg/day, methyldopa 750 mg/day combined with propranolol 240 mg/day, methyldopa 750 mg/day combined with practolol 600 mg/day, and placebo for four weeks each according to a random sequence. After four weeks of therapy the most effective treatment, methyldopa combined with propranolol, reduced lying and standing blood pressures by 36-5/21-4 mm Hg and 44-7/25 mm Hg respectively. Thic combination had similar effects to those of the combination of methyldopa with the cardioselective agent practolol except that it reduced lying diastolic pressure further. The combination was more effective than either treatment alone. No significant differences were found between the effects of propranolol, practolol, or methyldopa at the doses used.     

Lack of effect of oral magnesium on high blood pressure: a double blind study.

Seventeen unselected patients with mild to moderate essential hypertension and whose average supine blood pressure after two months'' observation with no treatment was 154/100 mm Hg were entered into a double blind randomised crossover study of one month''s treatment with magnesium aspartate (15 mmol magnesium/day) and treatment with placebo for a further month. This preparation of magnesium was well tolerated and did not cause diarrhoea. Despite a significant increase in plasma magnesium concentration and a significant increase in urinary excretion of magnesium while taking magnesium aspartate there was no fall in blood pressure compared with either treatment with placebo or values before treatment. The results provide no evidence for a role of dietary magnesium in the regulation of high blood pressure and are contrary to recent speculations.     

Moderate sodium restriction with angiotensin converting enzyme inhibitor in essential hypertension: a double blind study.

Fifteen unselected patients who had essential hypertension and whose average supine blood pressure when they were not receiving any treatment and their usual sodium intake was 162/107 mm Hg were treated with captopril 50 mg twice daily. After one month''s treatment their supine blood pressure had decreased to 149/94 mm Hg. They were then instructed to reduce their sodium intake to about 80 mmol(mEq)/day. After two weeks of moderate sodium restriction they were entered into a double blind randomised crossover study comparing the effect of 10 Slow Sodium tablets (100 mmol sodium chloride) with matching placebo tablets while continuing to take captopril and restrict sodium in their diet. After one month of taking placebo their mean supine blood pressure was 137/88 mm Hg with a urinary sodium excretion of 83 mmol/24 h, while after one month of taking Slow Sodium tablets their mean supine blood pressure was 150/97 mm Hg (p less than 0.001) with a sodium excretion of 183 mmol/24 h. The mean supine blood pressure during moderate sodium restriction therefore decreased by 9% and correlated significantly with the reduction in urinary sodium excretion. These results suggest that the combination of treatment with a moderate but practical reduction in sodium intake and an angiotensin converting enzyme inhibitor is effective in decreasing the blood pressure in patients with essential hypertension. This combined approach overcomes some of the objections that have been made to salt restriction alone and to converting enzyme inhibitors alone.     

Minoxidil for severe hypertension after failure of other hypotensive drugs.

Forty-four patients with severe hypertension who were resistant to treatment with more conventional hypotensive drugs or could not tolerate the side effects were treated with minoxidil, a potent peripheral vasodilator. A beta-blocking drug and a diuretic were used routinely to control, respectively, the tachycardia and fluid retention caused by minoxidil. During treatment the outpatient supine blood pressure fell from a mean of 221/134 mm Hg to 162/98 mm Hg. Eleven patients required additional or alternative hypotensive agents before blood pressure was adequately controlled. Side effects were minor, although the invariable hirsuties caused by minoxidil was unacceptable to three women. The possibility of cardiotoxic effects, raised by early studies in dogs, has not been excluded, and therefore this drug should be used only in patients with severe hypertension. In such patients minoxidil appears to be most effective.     

丹参酮ⅡA 磺酸钠注射液对原发性高血压患者血脂水平及内皮功能的影响

目的:研究丹参酮ⅡA磺酸钠注射液对原发性高血压患者血脂水平及内皮功能的影响。方法:选择2013年5月-2015年10月在我院首次诊断为原发性高血压的80例患者作为研究对象,根据治疗方法不同将入组患者随机分为实验组和对照组。实验组患者接受丹参酮ⅡA磺酸钠注射液联合口服降压药物治疗,对照组患者仅接受口服降压药物治疗,比较两者患者治疗前后的血压、肝肾功能、血脂水平以及内皮功能指标的变化。结果:治疗后,两组患者的收缩压、舒张压水平均低于治疗前,且实验组患者的收缩压、舒张压水平与对照组比较均无统计学差异。治疗后,两组患者的ALT、AST、Scr水平均与治疗前比较均无显著差异,且实验组患者的ALT、AST、Scr水平与对照组比较无统计学差异。治疗后,实验组患者的TC、TG、LDL水平明显低于治疗前(P0.05),对照组患者的TC、TG、LDL与治疗前比较无统计学差异(P0.05),实验组患者的TC、TG、LDL水平显著低于对照组(P0.05)。结论:丹参酮ⅡA磺酸钠注射液有助于改善原发性高血压患者的血脂代谢以及内皮功能,且对患者的肝肾功能无明显影响。     

Sodium restriction and blood pressure in hypertensive type II diabetics: randomised blind controlled and crossover studies of moderate sodium restriction and sodium supplementation.

OBJECTIVE--To determine the effect of moderate dietary sodium restriction on the hypertension of non-insulin-dependent (type II) diabetes. DESIGN--Randomised parallel controlled study of moderate sodium restriction for three months compared with usual diabetic diet, followed by randomised double blind crossover trial of sustained release preparation of sodium for one month versus placebo for one month in patients continuing with sodium restriction. SETTING--Patients attending diabetic outpatient clinic of city hospital. PATIENTS--Thirty four patients with established type II diabetes complicated by mild hypertension (systolic blood pressure greater than 160 mm Hg or diastolic pressure greater than 95 mm Hg on three consecutive occasions). Patients already taking antihypertensive agents (but not diuretics) not barred from study provided that criteria for mild hypertension still met. Conditions precluding patients from study were diabetic or hypertensive nephropathy, cardiac failure, and pregnancy. INTERVENTIONS--After run in phase with recordings at seven weeks, three weeks, and time zero patients were allocated at random to receive moderate dietary sodium restriction for three months (n = 17) or to continue with usual diabetic diet. Subsequently nine patients in sodium restriction group continued with regimen for a further two months, during which they completed a randomised double blind crossover trial of sustained release preparation of sodium (Slow Sodium 80 mmol daily) for one month versus matching placebo for one month. END POINT--Reduction in blood pressure in type II diabetics with mild hypertension. MEASUREMENTS AND MAIN RESULTS--Supine and erect blood pressure, body weight, and 24 hour urinary sodium and potassium excretion measured monthly during parallel group and double blind crossover studies. After parallel group study sodium restriction group showed significant reduction in systolic blood pressure (supine 19.2 mm Hg, erect 21.4 mm Hg; p less than 0.001) and mean daily urinary sodium excretion (mean reduction 60 mmol/24 h). There were no appreciable changes in weight, diabetic control, or diastolic pressure. No significant changes occurred in controls. In double blind crossover study mean supine systolic blood pressure rose significantly (p less than 0.005) during sodium supplementation (to 171 mm Hg) compared with value after three months of sodium restriction alone (159.9 mm Hg) and after one month of placebo (161.8 mm Hg). CONCLUSIONS--Moderate dietary restriction of sodium has a definite hypotensive effect, which may be useful in mild hypertension of type II diabetes.     

Antihypertensive treatment in pregnancy: analysis of different responses to oxprenolol and methyldopa.

One hundred and eighty three hypertensive pregnant women were randomly assigned to antihypertensive treatment with oxprenolol (96 women) or methyldopa (87 women). Control of hypertension was equivalent in both treatment groups, and in 64 (35%) cases hydralazine had to be added to the treatment to achieve the therapeutic goal (diastolic blood pressure below 85 mm Hg). Five perinatal deaths occurred, one in the oxprenolol group and four in the methyldopa group. Detailed analysis confirmed a previous report of greater fetal growth in the group treated with oxprenolol; this trend was present regardless of severity of hypertension and parity. With increasing duration of treatment the differences between the two groups diminished, and there was no difference after 10 weeks of treatment, a finding that may explain some of the reported discrepancies among therapeutic studies. As hypertension in pregnancy may pursue an accelerated course, necessitating urgent delivery, and there is no satisfactory method of predicting the duration of treatment in individual patients fetal benefit is most likely to be achieved by treatment with oxprenolol, provided that there is no maternal contraindication to treatment with beta blockers.     

Atenolol,methyldopa, and chlorthalidone in moderate hypertension.

Combined treatment with low doses of different drugs is widely used for moderate hypertension. The effects of atenolol and methyldopa at two dose levels and in combination at the lower doses were studied in patients with moderate hypertension on continuous treatment with moderate hypertension on continuous treatment with chlorthalidone. The mean reduction in standing blood pressures obtained with atenolol 150 and 300 mg/day was about 27/17 mm Hg and with methyldopa 750 and 1500 mg/day about 28/14 mm Hg. Combined treatment with atenolol 150 mg/day and methyldopa 750 mg/day for four weeks resulted in a reduction of 38/25 mm Hg. No difference was observed between the two doses of methyldopa. The lower dose of atenolol was better than the lower dose of methyldopa in reducing lying and standing diastolic blood pressures. These findings show that in patients on continuous treatment with chlorthalidone the addition of atenolol alone or methyldopa alone or of atenolol and methyldopa in combination is effective in the treatment of moderate hypertension.     

Factors related to first dose hypotensive effect of captopril: prediction and treatment.

The blood pressure response to the first dose of captopril (6.25 mg, 12.5 mg, or 25 mg) was measured in 65 treated, severely hypertensive patients. Mean supine blood pressure was 187/108 mm Hg immediately before captopril was given. Twenty one patients experienced a fall in supine systolic pressure greater than 50 mm Hg, including five whose pressure fell more than 100 mm Hg and two whose pressure fell more than 150 mm Hg. Six patients developed symptoms of acute hypotension, including dizziness, stupor, dysphasia, and hemiparesis. Percentage reductions in blood pressure were greatest in those with secondary hypertension (p less than 0.05), high pretreatment blood pressure (p less than 0.05), and high concentrations of plasma renin and angiotensin II (p less than 0.01). No significant correlation was found between fall in blood pressure and serum sodium concentration, age, renal function, and the dose of captopril given. A severe first dose effect cannot be consistently predicted in individual patients who have received other antihypertensive drugs for severe hypertension. Such patients should have close medical supervision for at least three hours after the first dose of captopril.     

Role of nifedipine in treatment of hypertension.

The efficacy of nifedipine in the treatment of hypertension was assessed in 15 patients whose hypertension continued while being treated with atenolol 100 mg and bendrofluazide 5 mg daily. Nifedipine was added in doses of 10, 20, and 30 mg three times daily in a placebo controlled, double blind trial. One patient was withdrawn from the trial because of severe postural hypotension with the highest dose. Erect and supine blood pressure in the remaining 14 patients were significantly reduced by all doses of nifedipine. The drug was well tolerated but plasma potassium fell by 0.3 mmol(mEq)/1 during treatment (p less than 0.05). Nifedipine is thus effective in the treatment of hypertension but should probably be used in combination with a potassium sparing diuretic.     

Hydrochlorothiazide-amiloride versus hydrochlorothiazide alone for essential hypertension: effects on blood pressure and serum potassium level

In a double-blind randomized controlled trial the effects on the blood pressure and the serum potassium concentration of hydrochlorothiazide-amiloride hydrochloride (Moduret) and hydrochlorothiazide alone were compared in 266 adults who were normokalemic and had a diastolic blood pressure greater than 95 mm Hg at the time of entry into the study. The mean ages (52.2 and 53.8 years) and the proportions of men (66% and 56%) in the groups given the combination drug and hydrochlorothiazide alone respectively were similar. In the group given the combination drug the mean blood pressure, measured while the patients were supine, and the mean serum potassium level fell significantly, from 156/99 to 138/88 mm Hg and from 4.23 to 3.91 mmol/L, after 8 weeks of treatment. In the other group both measures also fell significantly, the blood pressure from 157/99 to 138/87 mm Hg and the potassium level from 4.16 to 3.69 mmol/L. The proportions of patients in the two groups with hypokalemia (14% and 29% respectively), defined as a serum potassium level below 3.5 mmol/L, differed significantly (p = 0.0026), whereas the proportions with a potassium level exceeding 4.5 mmol/L (4.5% and 3.9% respectively) were similar. Thus, the combination drug reduced the blood pressure to the same extent as hydrochlorothiazide alone but significantly less often caused hypokalemia. In light of growing concerns about the cardiovascular complications of hypokalemia, hydrochlorothiazide-amiloride appears preferable to hydrochlorothiazide alone for the treatment of some patients with hypertension.     

Renin concentrations and effects of propranolol and spironolactone in patients with hypertension.

In a crossover study 32 patients with hypertension were randomly allocated to treatment with spironolactone 200 mg/day for two months, propranolol 320 mg/day for two months, and a combination of both drugs at half the dose. Between the treatments placebo was given for two months. Both spironolactone and propranolol lowered the blood pressure significantly in both positions. The initial plasma renin activity (PRA) levels ranged from 0-4 to 5-0 mug angiotensin I l-1 h-1, and there was a close correlation between these levels and the effects of the drugs: with increasing PRA the response to propranolol was better while the opposite was true for spironolactone. Spironolactone reduced the blood pressure more at eight than at four weeks, while no such difference could be shown for propranolol. Spironolactone and propranolol together decreased the blood pressure still further irrespective of the initial PRA. All patients achieved a normal supine blood pressure.     

Hypotensive Action and Side Effects of Clonidine-Chlorthalidone and Methyldopa-Chlorthalidone in Treatment of Hypertension

In an open, randomized, cross-over study the hypotensive action and side effects of clonidine-chlorthalidone and methyldopa-chlorthalidone combinations were compared. The diastolic morning blood pressure could be reduced to 95 mm. Hg or below in significantly more patients with clonidine than with methyldopa. Side effects, however, were more commonly encountered during the clonidine than during the methyldopa phase.     

Atenolol in essential hypertension during pregnancy.

OBJECTIVE--To determine the effect of atenolol on the outcome of pregnancy in women with essential hypertension. DESIGN--Prospective, randomised, double blind, placebo controlled study. SETTING--Hospital clinic. PATIENTS--33 Women with mild essential hypertension (systolic blood pressure 140-170 mm Hg or diastolic pressure 90-110 mm Hg on two occasions at least 24 hours apart) consecutively referred to two obstetric medical clinics. Four patients in the placebo group were withdrawn from the study: control of blood pressure was inadequate in two, one developed breathlessness, and one changed her mind about participating. The mean gestation in the 29 remaining women on entry to the study was 15.9 weeks. MAIN OUTCOME MEASURES--Blood pressure and birth weight. INTERVENTION--14 Women received placebo. 15 Women received atenolol 50 mg daily initially, increasing until either the blood pressure was less than 140/90 mm Hg or a dose of 200 micrograms daily was reached. RESULTS--The mean blood pressure on entry was 148/86 mm Hg in the group given atenolol and 144/86 mm Hg in the group given placebo. During treatment the mean diastolic pressure was significantly reduced by atenolol compared with placebo (to 74 v 81 mm Hg; difference in means (95% confidence interval) 7.0 (2.9 to 10.0) mm Hg) but the effect on systolic pressure was marginal (132 v 136 mm Hg; 4.0 (-1.4 to 8.6) mm Hg). Babies in the atenolol group had a significantly lower birth weight than those in the placebo group (2620 g v 3530 g; 910 (440 to 1380)g). CONCLUSION--Atenolol given from the end of the first trimester in patients with mild hypertension is associated with intrauterine growth retardation. When taken in conjunction with the results of a previous study in which methyldopa was given these findings indicate that benefit is unlikely to result from treating mild essential hypertension in pregnancy.     

阿托伐他汀钙对无动脉硬化原发性高血压患者血脂和颈动脉内膜中层厚度的影响

目的:研究阿托伐他汀钙对无动脉硬化原发性高血压患者血脂和颈动脉内膜中层厚度(cal MT)的影响。方法:选取2013年7月到2014年7月我院收治的无动脉硬化原发性高血压患者100例,按照随机数字表法将患者分为研究组和对照组,每组50例,对照组给予常规治疗,研究组在对照组的基础上给予阿托伐他汀钙治疗,治疗时间均为6个月。比较治疗前、治疗后两组血脂、血压以及cal MT。结果:研究组治疗后总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)显著降低,高密度脂蛋白胆固醇(HDL-C)显著增高,且显著优于对照组治疗后,比较差异具有统计学意义(P0.05);两组治疗后血压均显著低于治疗前,比较差异具有统计学意义(P0.05),且治疗后研究组显著优于对照组,比较差异具有统计学意义(P0.05);治疗后研究组cal MT显著优于治疗前,且优于对照组,比较差异具有统计学意义(P0.05)。结论:阿托伐他汀钙治疗无动脉硬化原发性高血压能显著改善患者血脂水平,降低其cal MT,对预防患者动脉粥样硬化具有重要意义。