Lisinopril versus atenolol: Decrease in systolic versus diastolic blood pressure with converting enzyme inhibition

In a multicenter, parallel, double-blind study, lisinopril, a new converting enzyme inhibitor, was compared with atenolol in the treatment of mild to moderate essential hypertension. Four hundred ninety patients were randomized to once-a-day treatment with lisinopril 20 mg or atenolol 50 mg for 4 weeks, and the doses of lisinopril or atenolol were increased at 4-week intervals up to 80 mg or 200 mg, respectively, if sitting diastolic blood pressure (SDBP) was not well controlled. Lisinopril and atenolol reduced SDBP to a similar extent. All reductions from baseline in sitting diastolic and systolic blood pressure were significant (p less than 0.01). Lisinopril produced a significantly greater reduction (p less than 0.01) in sitting systolic blood pressure (SSBP) than atenolol. The predominant reduction in SSBP could not be explained on the basis of age, race, or severity of hypertension. It is suggested that the increase in arterial compliance reported for converting enzyme inhibitors could explain the predominant decrease in systolic blood pressure.     

Comparison of antihypertensive therapies by noninvasive techniques

We compared the antihypertensive effects of the beta-blocker atenolol and the converting enzyme inhibitor lisinopril during 12 weeks of treatment in patients with mild to moderate essential hypertension. Atenolol (n = 10) significantly decreased conventionally measured blood pressure from 144/103 to 135/93 mm Hg and lisinopril (n = 9) from 150/104 to 130/92 mm Hg. Based on data derived from automated 24-h ambulatory blood pressure monitoring, atenolol decreased the average whole-day systolic pressure by 18 +/- 6 mm Hg (p less than 0.02) and the diastolic pressure by 11 +/- 2 mm Hg (p less than 0.01). Lisinopril produced decreases of 27 +/- 5 mm Hg (p less than 0.01) and 13 +/- 2 mm Hg (p less than 0.001). Examination of the 24-h blood pressure patterns showed that the efficacies of the two drugs were similar. Each appeared to be effective throughout the whole-day monitoring period, although only lisinopril significantly decreased blood pressure during the final four-h period (4 AM to 8 AM) preceding the next day's dose. Neither drug produced significant echocardiographic changes in left ventricular wall thickness or muscle mass during the short-term treatment. Lisinopril and atenolol effectively decrease blood pressure during a 24-h period. Moreover, we found that automated whole-day blood pressure monitoring is a useful tool for comparing the efficacy and duration of action of differing antihypertensive agents.     

Reproducibility of ambulatory blood pressure measurements in essential hypertension

BACKGROUND: Data on the reproducibility of serial measurements of ambulatory blood pressure in hypertensive patients are lacking. The purpose of this study was to examine (1) the reproducibility of four consecutive ambulatory blood pressure measurements, and (2) the reproducibility of nocturnal falls in blood pressure in hypertensive patients. METHODS: Twenty patients with mild to moderate essential hypertension underwent four separate ambulatory blood pressure monitorings, on the same day of the week, at 30-day intervals. Antihypertensive therapy was discontinued for 2 weeks before each recording. Comparing the mean values of blood pressure over 24h, as well as diurnal, nocturnal and hourly periods, among the four recordings determined the reproducibility of blood pressure measurements. A day/night difference in mean systolic and in mean diastolic blood pressure defined the nocturnal fall in blood pressure. RESULTS: No significant differences were observed in either hourly, 24-h, diurnal or nocturnal systolic blood pressure, diastolic blood pressure and heart rate, or in the nocturnal fall in systolic and diastolic blood pressure among the four recordings. CONCLUSIONS: Hourly systolic blood pressure, diastolic blood pressure, heart rate, and nocturnal fall in blood pressure were reproducible in four ambulatory blood pressure monitorings recorded over 4 months. These findings suggest that ambulatory blood pressure monitoring is a reliable tool to monitor blood pressure changes.     

Comparison of lisinopril versus atenolol for mild to moderate essential hypertension.

The antihypertensive effects and safety profiles of lisinopril (10 to 40 mg) and atenolol (50 to 100 mg) were compared in a randomized, double-blind, parallel group trial in 144 patients with essential hypertension. After 8 weeks of therapy, seated blood pressure (BP) decreased by 26/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol. Lisinopril produced a greater reduction (p less than 0.05) in sitting systolic BP than did atenolol. Standing BP decreased by 25/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol. No important changes in hematologic and biochemical profiles were seen with either drug. Eleven patients, 7 receiving lisinopril and 4 receiving atenolol, were withdrawn because of adverse experiences; another 3 patients defaulted during treatment, 1 in the lisinopril group and 2 in the atenolol group. Both drugs were well-tolerated and are therefore suitable for first-line therapy in essential hypertension.     

Effect of bedtime melatonin ingestion on blood pressure of normotensive subjects

OBJECTIVE: To determine whether the evening intake of 5 mg melatonin affects 24 h arterial blood pressure and heart-rate profiles. METHODS: Twenty-one young normotensive subjects were administered placebo or melatonin for 4 weeks, according to a cross-over double-blind design, and were subjected to ambulatory blood pressure monitoring on the first and last days of each treatment period. RESULTS: The chronic melatonin intake caused a decrease in systolic blood pressure throughout the 24 h period (109.1+/- 7.2 versus 113.6 +/- 8.15 mmHg, P < 0.05), a decrease in diastolic blood pressure (by 6.4 mmHg, P < 0.05) limited to the second half of the night, a slight lowering of the heart rate during the diurnal hours (78.6 +/- 7.6 versus 81.5 +/- 10.1 beats/min, P < 0.05) and an acceleration of a similar degree during the second half of the night. The slight hypotensive action and the diurnal heart-rate lowering may be explained theoretically in terms of various complex and synergistic mechanisms that so far have been verified only in experimental studies on animals. The etiology of the nocturnal heart-rate acceleration remains unknoiwn. Further controlled studies are needed in order to better understand the cardiovascular effects of melatonin and to evaluate possible pharmacologic interactions. CONCLUSION:     

A study of the effects of lisinopril when used in addition to atenolol.

A double-blind, parallel group multicentre study was carried out to compare the effects of adding once daily treatment with lisinopril 10 or 20 mg and placebo to the treatment of 100 patients whose blood pressure was inadequately controlled with once daily atenolol 50 mg. Following a two-week run-in period, patients with a lying DBP between 95 mmHg and 115 mmHg were randomised to either lisinopril 10 mg or placebo once daily for four weeks. Blood pressure measurements were made approximately 24 h after the previous dose of study medication. After four weeks' treatment the dose of study medication was doubled for those patients whose lying DBP was greater than or equal to 90 mmHg and a final assessment was made after a further two weeks of treatment. Overall, six weeks' treatment with lisinopril produced a greater fall in lying blood pressures than placebo when added to atenolol therapy. The difference in favour of the additional ACE inhibitor therapy was 7.1 +/- 2.6/5.4 +/- 1.5 mmHg (mean +/- SEM) (P less than 0.01). Standing blood pressures showed similar behaviour in favour of the additional ACE inhibitor treatment (7.6 +/- 2.4/4.7 +/- 1.6 mmHg) (P less than 0.005). Heart rate was not altered significantly by either lisinopril or placebo treatment. The addition of lisinopril to treatment with atenolol produced a slight increase in the reported number of adverse events compared with placebo. The results of this study indicate that the addition of lisinopril 10-20 mg once daily to treatment with a beta-adrenoceptor blocking drug produces a worthwhile decrease in blood pressure in patients not responsive to beta-blocker therapy alone.     

Sustained antihypertensive actions of a dual angiotensin-converting enzyme neutral endopeptidase inhibitor, sampatrilat, in black hypertensive subjects.

Our objective was to evaluate the safety and antihypertensive efficacy of sampatrilat, a novel dual inhibitor of both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), in subjects poorly responsive to ACE inhibitor monotherapy. The ability of sampatrilat (50 to 100 mg daily) (n = 28) to lower blood pressure was compared with that of the ACE inhibitor lisinopril (10 to 20 mg daily) (n = 30) using a double-blind, randomized, parallel group study design over a 56-day treatment period in black hypertensives. Changes in systolic (SBP) and diastolic (DBP) blood pressure were determined using repeated ambulatory blood pressure (ABP) monitoring. Both sampatrilat and lisinopril decreased plasma ACE concentrations after 28 and 56 days. The decrease in plasma ACE concentrations (U/L) was greater after lisinopril (-9.33 +/- 0.52) as compared with sampatrilat (-6.31 +/- 0.70) (P = .0001) therapy. Lisinopril, but not sampatrilat, increased plasma renin activity. Lisinopril produced a transient decrease in mean 24-h ABP (mm Hg) at 28 days (SBP = -9.0 +/- 2.3, DBP = -5.7 +/- 1.3; P < .01), which returned to pretreatment values by 56 days of therapy. Alternatively, sampatrilat produced a sustained decrease in mean ABP over the 56-day treatment period (day 28: SBP = -7.3 +/- 1.8, DBP = -5.2 +/- 1.2; P < .01: day 56: SBP = -7.8 +/- 1.5; DBP = -5.2 +/- 0.95; P < 0.01) with a greater treatment effect on DBP than that of lisinopril at day 56 (P = .05). Treatment-emergent adverse events were noted to be similar between both treatment groups. We conclude that the antihypertensive actions of ACE/NEP inhibitor monotherapy in black subjects offers a novel therapeutic approach to patients otherwise resistant to the sustained antihypertensive actions of ACE inhibitor monotherapy.     

The effect of amlodipine on ambulatory blood pressure in hypertensive patients

Certain high-risk populations, such as diabetics and blacks, have sustained elevation in blood pressure and heart rate throughout the day and night, with blunting of the usual diurnal variability pattern. This may contribute to their higher incidence of left ventricular hypertrophy (blacks) and cardiovascular complications (diabetics). Hypertensives who maintain a diurnal pattern of blood pressure variation still exhibit higher daytime and nocturnal blood pressure levels than normotensives. Thus, to achieve maximum effectiveness in treating hypertension, 24-hour control of blood pressure is necessary. Antihypertensive agents should effectively reduce blood pressure consistently throughout a 24-hour period. The objective of this study was to assess the effects of amlodipine, 5 mg once daily, on blood pressure measured by 24-hour ambulatory monitoring in a randomized, double-blind, placebo-controlled single-site study. Patients with mild-to-moderate essential hypertension were randomized to receive amlodipine (n = 11) or placebo (n = 5) in a 2:1 ratio. A 4-week single-blind placebo run-in period was followed by a 4-week double-blind phase. Ambulatory monitoring of blood pressure was carried out for 24 hours at the end of each 4-week phase. Patients receiving amlodipine had significantly lower blood pressure compared with placebo 24 hours after the last dose (supine blood pressure −25.1/−10.1 mm Hg; standing blood pressure −21.2/−9.7 mm Hg) after 4 weeks of treatment. This effect was clearly demonstrated by the 24-hour postdose measurement and the mean blood pressure over the 24-hour interval as measured by ambulatory recordings. The mean hourly ambulatory recordings showed that amlodipine maintained both diastolic and systolic pressures below the baseline levels at every hour during the 24-hour observation period. Nine of 10 evaluable patients (90%) on amlodipine responded vs only 1 of 5 patients (20%) on placebo. The decrease in blood pressure for the amlodipine patients was not accompanied by a significant increase in pulse rate. Amlodipine was well tolerated; possibly drug-related side effects of intermittent headache and nocturia were experienced by 1 patient each; the latter had been present during the placebo run-in phase. Amlodipine is effective, well tolerated, and may be administered once daily for effective 24-hour blood pressure control.     

Effects of mild physical activity, atenolol and the combination on ambulatory blood pressure in hypertensive subjects.

OBJECTIVE: To evaluate whether beta-blocker treatment could enhance the effect of a mild physical training programme upon blood pressure. DESIGN AND METHODS: In 12 hypertensive subjects (mean age: 40.3 years) a prospective randomized Latin square-design trial was performed with three treatments: physical training and placebo tablets; atenolol 50 mg once a day and inactivity; and physical training and atenolol 50 mg once a day. RESULTS: Training significantly increased maximal ventilatory oxygen consumption (VO2MAX), and there was a decrease in ambulatory diastolic blood pressure (DBP) which did not reach statistical significance. Atenolol alone significantly reduced ambulatory systolic blood pressure (SBP) and DBP. Atenolol alone did not reduce VO2MAX. The combination of training and atenolol resulted in an increase in VO2MAX compared with atenolol alone, but no additional significant fall in blood pressure. CONCLUSIONS: Atenolol did not enhance the effect of physical training upon blood pressure and had little if any effect upon the training-induced increase in exercise tolerance.     

Treatment of non-dipper hypertension with bedtime administration of valsartan

BACKGROUND: Previous results have indicated that valsartan administration at bedtime, as opposed to upon wakening, may improve the diurnal: nocturnal ratio of blood pressure without loss in 24-h coverage and efficacy. OBJECTIVES: To investigate the administration time-dependent antihypertensive efficacy of valsartan in non-dipper patients. METHODS: We studied 148 non-dipper patients with grade 1-2 essential hypertension, aged 53.0+/-12.6 years, who were randomly assigned to receive valsartan (160 mg/day) as a monotherapy either on awakening or at bedtime. Blood pressure was measured every 20 min during the day and every 30 min at night for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per subject basis. RESULTS: The significant blood pressure reduction after 3 months of valsartan (P<0.001) was similar for both treatment times (13.1 and 8.5 mmHg reduction in the 24-h mean of systolic and diastolic blood pressure with morning administration; 14.7 and 10.3 mmHg with bedtime administration; P>0.126 for treatment-time effect). The diurnal: nocturnal ratio of blood pressure was significantly increased only when valsartan was administered before bedtime, which resulted in 75% of the patients in this group reverting to dippers, a significant increase in the percentage of patients with controlled blood pressure over 24 h, and a reduction in urinary albumin excretion. CONCLUSIONS: In non-dipper hypertensive patients, dosing time with valsartan should be chosen at bedtime, for improved efficacy during the nocturnal resting hours, as well as the potential associated reduction in cardiovascular risk.     

Decrease in urinary albumin excretion associated with the normalization of nocturnal blood pressure in hypertensive subjects

Previous results have indicated that valsartan administration at bedtime as opposed to on wakening improves the diurnal/nocturnal ratio of blood pressure without loss in efficacy and therapeutic coverage. We hypothesized that increasing this ratio could reduce microalbuminuria. We conducted a prospective, randomized, open-label, blinded endpoint trial on 200 previously untreated nonproteinuric patients with grade 1 to 2 essential hypertension, assigned to receive valsartan (160 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured by ambulatory monitoring for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per-subject basis. The significant blood pressure reduction after 3 months of therapy was similar for both treatment times. The diurnal/nocturnal blood pressure ratio was unchanged after valsartan on awakening, but significantly increased from 7.5 to 12.2 (P<0.001) when valsartan was administered at bedtime. Urinary albumin excretion was significantly reduced by 41% after bedtime treatment. This reduction was independent of the 24-hour blood pressure decrease but highly correlated with the decrease in nocturnal blood pressure and mainly with the increase in diurnal/nocturnal ratio (P<0.001). Bedtime valsartan administration improves the diurnal/nocturnal blood pressure ratio to a more dipper profile. This normalization of the circadian blood pressure pattern is associated with a significant decrease in urinary albumin excretion and plasma fibrinogen, and could thus reduce the increased cardiovascular risk in nondipper hypertensive patients.     

The antihypertensive effect and safety of lisinopril in patients with mild to moderate essential hypertension. A Belgian multicenter study

The safety and efficacy of lisinopril in the treatment of mild to moderate essential hypertension was evaluated by Belgian general practitioners in patients whose hypertensive condition remained uncontrolled by previous treatment and/or in whom the prior drug regimen was not tolerated. In this 8-week study, 3060 eligible patients were initially treated with 20 mg lisinopril once daily; this dose was increased to 40 mg if diastolic blood pressure (DBP) was greater than 90 mm Hg after 4 weeks. Lisinopril monotherapy in the 1902 patients completing the trial resulted in marked reductions of systolic (SBP) and DBP from 172.5/102.4 mm Hg at baseline to 147.4/86.6 mm Hg by week 8. More than 90% of patients achieved a DBP less than 95 mm Hg. The decrease in blood pressure was similar in patients older and younger than 65 year of age. Only about 20% of patients required an increase in their daily intake of lisinopril to 40 mg. Treatment was well tolerated and the profile of adverse events was similar to the pattern found with other nonsulfydryl angiotensin converting enzyme inhibitors. Tolerance in the elderly was similar to that experience by hypertensives under 65 years of age. Thus, lisinopril at 20 or 40 mg once daily proved both well tolerated and effective in reducing blood pressure in patients with mild to moderate essential hypertension.     

Atrial natriuretic peptide and 24 h blood pressure

BACKGROUND: Atrial natriuretic peptide (ANP) is a hormone involved in the cardiovascular modulation of blood pressure and volume homeostasis. OBJECTIVE: To compare ANP levels in normotensives and hypertensives and to correlate ANP levels with ambulatory blood pressure parameters. METHODS: Plasma samples for ANP determination (using a double-antibody radioimmunoassay Kit) were obtained from 33 consecutive subjects (24 hypertensives, nine normotensives) who had rested supine for 30 min. Afterwards, all of the subjects were subjected to 24 h non-invasive blood pressure monitoring. We found no significant difference between the two groups with regard to ANP levels (95.1+/-29 versus 96.9+/-33 pg/ml, in normotensives and hypertensives, respectively). Also, when hypertensive patients were divided according to their family history of hypertension, ANP levels were similar. There was no correlation between the ANP level and the pre-sampling blood pressure or between the ANP level and the following ambulatory blood pressure monitoring parameters: 24 h, diurnal and nocturnal systolic and diastolic blood pressures, systolic and diastolic loads, nocturnal blood pressure reduction and blood pressure variation coefficients. CONCLUSION: Both the pre-sampling blood pressure and ambulatory monitoring results (sustained blood pressures and pressure variations during the 24 h period) do not seem to influence basal ANP levels in patients with hypertension. These data do not account for a role of this peptide in cardiovascular control, in hypertension.     

Effects of lisinopril vs hydralazine on left ventricular hypertrophy and ambulatory blood pressure monitoring in essential hypertension

In order to compare the long-term effects on ambulatory bloodpressure and left ventricular hypertrophy of hydralazine andlisinopril we studied 30 patients, all , nales, still hypertensive(diastolic blood pressure 95 mmHg) despite combined beta-blockerldiuretictherapy and with echocardiographic evidence of left ventricularhypertrophy (left ventricular mass index 131 g. m^–1)They were randomized to receive hydralazine slow release 50mg twice daily or lisinopril 20mg once daily in addition toprevious therapy (atenolol 50 mglchlorthalidone 125 mg) for6 months. Casual blood pressure, non-invasive ambulatory bloodpressure monitoring (ABPM), M-mode echocardiogram, plasma reninactivity and plasma catecholamines were evaluated before therandomization and after 6 months of treatment. Both drugs significantlyreduced casual as well as daytime systolic and diastolic bloodpressure, without statistical differrences between the two treatments.Lisinopril was sign more effective than hydralazine in reducingnight-time systolic and diastolic blood pressure. Plasma norepinephrinewas significantly reduced by lisinopril and increased by hydralazine.Left ventricular mass was significantly reduced by lisinoprilbut not by hydralazine. The results of linear regression andmultiple regression analysis suggested that the lisinopril-induceddecrease in both day- and night-time blood pressure might accountfor the regression of left ventricular hypertrophy, whereasthe lack of left ventricular hypertrophy regression during hydralazinetreatment could be due mainly to the reflex sympathetic activationinduced by the drug.     

Use of a mild sedative helps to identify true non-dippers by ABPM: a study in patients with diabetes mellitus and hypertension

BACKGROUND: The interplay between the continuity or quality of sleep and diurnal variation in blood pressure has not been directly examined before. We examined the influence of a mild, non-hypotensive sedative on nocturnal dipping. DESIGN: This was a randomized, single-blind study. SETTING: The study took place in an out-patient clinic in an academic hospital. INTERVENTION: Zolpidem 10 mg or placebo was given randomly for the first or second night, and ambulatory blood pressure monitoring was instigated for 48 h. PATIENTS: The population under study comprised 96 male patients with type 2 diabetes mellitus and hypertension (mean age 54 +/- 6 years, mean blood pressure 158/94 +/- 9/6 mmHg). MAIN OUTCOME MEASURE: Nocturnal dipping (nocturnal blood pressure >/= 10% lower than daytime pressure) was found in 71% of the patients taking the sedative compared with 27% of those on placebo (P=0.001). RESULTS: On placebo, non-dippers and dippers had similar profiles of cardiovascular risk parameters. In contrast, non-dippers taking zolpidem had significantly higher values for most cardiovascular risk parameters compared with dippers: higher systolic blood pressure, higher low-density lipoproteins, lower high-density lipoproteins, higher serum creatinine, a higher urinary albumin:creatinine ratio, higher serum insulin and insulin resistance. CONCLUSION: The use of a mild sedative during ambulatory blood pressure monitoring may help to identify the patients with a very high cardiovascular risk. These are the patients with a blunted nocturnal hypotension despite sedation.     

Stability of diurnal blood pressure rhythm during 48-hour ambulatory blood pressure monitoring

Evaluation of nocturnal blood pressure (BP) fall is important for prognosis and selection of antihypertensive therapy. We assessed stability of BP diurnal rhythm in 56 hospitalized hypertensive patients by means of 48-hour ambulatory BP monitoring. According to the degree of congruence of BP fall during two nights of monitoring the following groups of patients were distinguished: with similar diurnal BP rhythm in both nights (72% of all patients, including 42% with sufficient and 30% with insufficient nocturnal BP decline), with different diurnal BP rhythms - with sufficient fall of BP in one night and insufficient in another (28% of all patients). BP variability in all patients did not change and could be considered very stable. Thus when insufficient nocturnal BP fall is detected its stability should be confirmed by repeat BP monitoring.     

Effect of atenolol or enalapril on diurnal changes of blood pressure in Japanese mild to moderate hypertensives: a double-blind, randomised, crossover trial

This randomised, double-blind, crossover study compared enalapril 5 mg, and atenolol 50 mg, each dosed once daily for 4 weeks, and investigated casual and diurnal BP changes using 24 hour ambulatory BP monitoring. Both atenolol and enalapril satisfactorily lowered BP during the day and no excessive falls occurred at night. The tendency for BP to increase during the day and decrease at night was maintained during both active periods. Pulse rate was reduced only by atenolol throughout 24 hours. The BP increase observed 2 hours after rising in the morning was suppressed by atenolol but not by enalapril. Both drugs reduced the rates of systolic (greater than or equal to 160 mmHg) and diastolic (greater than or equal to 95 mmHg) BP increases to half of those during placebo. The frequency with which diastolic BP increased above these limits was less during the atenolol period. The difference in BP between a hospital casual reading and the mean 24 hour ambulatory reading was reduced only by atenolol. Furthermore, only atenolol suppressed the BP and pulse rate increases on exercise.     

肾性高血压患者的动态血压昼夜节律

本研究应用２４小时无创性全自动动态血压记录仪观察了６７例受试对象，其中肾实质性高血压（ＲＰＨＴ）１２例；肾血管性高血压（ＲｖＨＴ）Ⅱ例；Ⅰ～Ⅱ期原发性高血压（ＥＨＴ）４４例。结果表明，各组受试者的偶测血压均明显高于动态血压。ＲＰＨＴ和ＲＶＨＴ的昼夜节律均明显减弱，收缩压和舒张压的夜间下降值均明显小于原发性高血压患者，夜间下降率低于１０％者的比率却明显高于原发性高血压患者．ＥＨＴ的动态血压呈夜间下降、白昼上升的节律性。     

A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of lisinopril for children with hypertension

BACKGROUND: Despite widespread use in hypertensive children, the safety and effectiveness of lisinopril had not been previously tested in a controlled study. METHODS: This study explored the dose-response relationship and safety of lisinopril in 115 hypertensive children, aged 6 to 16 years. Patients were randomized in a double-blind fashion for 2 weeks to one of three doses by body weight at baseline: <50 kg: low (0.625 mg), middle (2.5 mg), high (20 mg), and > or =50 kg: low (1.25 mg), middle (5 mg), high (40 mg). The dose-response for lisinopril was evaluated by analyzing the change in slope in sitting diastolic and systolic blood pressure (BP) by dose after 2 weeks of therapy compared to baseline. Patients then entered a double-blind withdrawal, where patients were either switched to placebo or continued their current lisinopril treatment for up to 2 weeks. Patients completed period II when their BP returned to baseline. Antihypertensive effectiveness, between placebo and lisinopril was determined for all doses. Adverse events were carefully monitored. RESULTS: There was a dose-response relationship between the lowest and each of the higher doses of lisinopril. Blood pressure in the placebo group increased after withdrawal of lisinopril. The dose-response relationship was consistent across all subgroups (ie, age, Tanner stage, ethnicity, gender). CONCLUSIONS: Lisinopril, once daily, is an effective and well-tolerated antihypertensive in children aged 6 to 16 years. An initial dose of 0.07 mg/kg, administered once daily, effectively lowered BP within 2 weeks. Blood pressure was reduced in a dose-dependent fashion.     

Home Blood Pressure Monitoring and Changes in Plasma Catecholamines During Once or Twice Daily Treatment with Atenolol in Patients with Mild Hypertension

Summary: Home blood pressure monitoring and changes in plasma catecholamines during once or twice daily treatment with atenolol in patients with mild hypertension. B. P. McGrath, L. J. Beilin, T. Schofield, C. R. Benedict, N. P. Barker and R. Cooper, Aust. N.Z. d. Med., 1979, 9, pp. 374–381.
1. The effects of atenolol on diurnal blood pressure control, heart rate and plasma catecholamines were studied in nine hypertensive, six of whom also received diuretics. The patients completed a double-blind trial in which the effects of once and twice daily administration of atenolol were compared with placebo.
2. Atenolol (100 mg) given once a day produced significant reduction in diurnal blood pressures recorded at home but the effect was slightly less than either 50 mg given twice a day or 200 mg once a day.
3. Effects on heart rate and blood pressure were seen within 36 hours of the first dose, and were near maximal at 72 hours. After cessation of the drug, mean resting heart rate increased gradually and reached pre-treatment levels five days later, suggesting strong tissue binding of atenolol. Blood pressure increased more slowly over 8–10 days.
4. Plasma noradrenaline levels were increased at rest with atenolol. This argues strongly against the antihypertensive effect of atenolol being due to a reduction of sympathetic nerve activity.
5. Once daily administration of atenolol in this group of patients with mild hypertension produced satisfactory diurnal blood pressure control and beta blockade without "rebound" hypertension on cessation of therapy.