比索洛尔、拉西地平和赖诺普利对高血压病患者24小时血压的影响

目的比较比索洛尔、拉西地平和赖诺普利对２９例高血压病患者的降压疗效。方法采用随机、单盲和交叉的方法，运用２４小时动态血压监测。结果三药均能显著降低血压，彼此间降低偶测血压的幅度无显著差异。比索洛尔和拉西地平降低２４小时平均和白天平均血压的幅度大于赖诺普利。三药均能有效控制清晨血压高峰期的血压，它们的降压谷／峰比值都超过６５％。结论比索洛尔、拉西地平和赖诺普利均可每日服用１次，前二药控制２４小时血压及清晨醒后的高峰期血压较后者为佳。     

Different hemodynamic (24-h ambulatory blood pressure monitoring) and renin-inhibiting effect of a 1-week treatment with enalapril and lisinopril.

Ambulatory blood pressure and heart rate monitoring were used for comparing the antihypertensive effect of a 1-week treatment with enalapril and lisinopril 10 mg once daily (double-blind crossover placebo-controlled study). Twelve outpatients with mild to moderate hypertension were treated. Both drugs had a significant and identical hypotensive effect. Neither drug affected the diurnal rhythm of blood pressure or heart rate. Therefore the two drugs are equipotent antihypertensive agents. Both drugs inhibited ACE activity to a highly significant extent, but in this regard lisinopril was more effective than enalapril. However, lisinopril's greater ACE inhibition was not accompanied by a greater hypotensive effect. The clinical value of this difference is not yet established.     

Comparison of the smoothness index,the trough : peak ratio and the morning : evening ratio in assessing the features of the antihypertensive drug effect

OBJECTIVE: To provide a direct comparison of the trough : peak ratio (TPR), the morning : evening home blood pressure ratio (MER) and the smoothness index (SI) in assessing the features of the antihypertensive drug effect. PATIENTS AND METHODS: A total of 27 untreated hypertensives were randomized to receive lisinopril 20 mg o.d. or losartan 50 mg o.d. for 5 weeks and were subsequently crossed-over to the alternative treatment for a second 5-week period. Twenty-four hour ambulatory and 5-day home blood pressure were monitored before randomization and at the end of each treatment period. TPR, MER and SI were calculated for each drug for the total study population and for responders only. RESULTS: When all patients were considered, lisinopril provided higher values of TPR [0.63/0.66 for systolic/diastolic blood pressure (SBP/DBP)], MER (1.02/0.77) and SI (1.01/0.87) than losartan (0.35/0.51, 0.60/0.60 and 0.64/0.53, respectively). Analysis of responders only, again showed a clear advantage of lisinopril over losartan in TPR (0.77/0.67 versus 0.44/0.47, respectively) and MER (0.86/0.87 versus 0.48/0.61), whereas there was no difference in SI (1.25/1.13 for lisinopril versus 1.11/1.12 for losartan). CONCLUSIONS: These data suggest that the assessment of the duration of the antihypertensive drug effect provided by the MER is consistent to that by the TPR and that two drugs with different levels of TPR and MER may have the same level of SI. It appears that the SI is not simply a more reliable index of the features of the antihypertensive drug effect, but offers a different type of information complementary to that provided by the TPR and the MER, in regard to the homogeneity and the magnitude but not the duration of the antihypertensive effect.     

Lisinopril versus enalapril: evaluation of trough:peak ratio by ambulatory blood pressure monitoring.

In 34 out-patients with essential hypertension, the antihypertensive effect and the trough-to-peak ratios of once-daily enalapril or lisinopril were compared by ambulatory blood pressure monitoring (ABPM) according to a crossover design. The drug dose was titrated and a thiazide diuretic was added if necessary to attain a target office BP of less than 140/90 mm Hg. Both drugs significantly lowered BP but the effect of lisinopril was greater (P < 0.009): day- and night-time mean BP fell from 152/98 and 135/84 mm Hg, respectively to 133/85 and 118/74 mm Hg with enalapril and to 129/83 and 116/70 mm Hg with lisinopril. BP goal was reached with an average dose of 18 mg enalapril with 8 mg hydrochlorothiazide and with 17 mg lisinopril combined with 6 mg diuretic. Trough:peak ratio values, which were calculated after Fourier analysis of ABPM data in individual patients, were independent of drug dose. The combination with the diuretic resulted in slightly higher trough:peak ratios than with ACE inhibitor monotherapy, but the difference was not significant. The median trough:peak ratio in patients when using enalapril-based therapy was 0.48 and, when taking lisinopril-based treatment, it was 0.65 (n = 28, P < 0.005). A significant correlation was found between trough:peak ratio and changes in daytime mean arterial pressure (MAP; Spearman r= 0.43) and night-time MAP (r= 0.66). When 24-h ABPM was performed starting 24 h after last drug intake, both ACE inhibitors still had a significant antihypertensive effect (P < 0.001), which was similar for both drugs. Eleven patients reported minor side effects. Four patients stopped ACE-inhibitor treatment because of cough. The data show that lisinopril has a longer duration of action than enalapril.     

The importance of 24-h blood pressure control

The primary goal of antihypertensive therapy is to restore blood pressure to normal levels and to prevent the complications associated with hypertension. In order to maximize these goals by improving patient compliance, clinical researchers have focused on developing antihypertensive agents that can be given once daily. These agents provide many advantages over multiple-dose daily therapies, but it should not be assumed that they are all equivalent in providing adequate blood pressure control over the full 24-h dosing interval. Ambulatory blood pressure monitoring has uncovered important differences in commonly used once-daily therapies and has provided additional insights into the cardiovascular risks associated with high blood pressure loads and blood pressure variability. In addition to ambulatory blood pressure monitoring data, the calculated trough:peak ratio provides useful information on an agent's ability to provide smooth and consistent blood pressure control. Using such assessments, it has been found that agents with a trough:peak ratio > or = 0.50 are better able to control blood pressure over the full 24h while maintaining natural circadian patterns. Ambulatory blood pressure monitoring studies assessing a recently introduced class of antihypertensive drugs, the angiotensin receptor blockers, have demonstrated 24-h efficacy with once-daily dosing, particularly with the newer agents.     

Importance of various methods of blood pressure measurement in clinical trials

Ambulatory blood pressure (ABP) monitoring and self-measurement of blood pressure (BP) are more reproducible than clinic BP measurement, minimize the white coat effect, and can reduce the sample size necessary to demonstrate the efficacy of a drug in clinical trials. For many years, the trough:peak ratio has been considered the key index for demonstrating the efficacy of antihypertensive agents. However, several potential problems are associated with the use of this index, and ABP monitoring makes it possible to examine changes in BP over the entire 24-hour period, not only at a preset time of peak effect and at the end of the dosing interval. The smoothness index provides more comprehensive information on the 24-hour BP control with treatment and avoids part of the problems encountered with the trough:peak ratio. One simple way to summarize the results of ABP monitoring in clinical trials is to provide the mean 24-hour BP difference from placebo and the BP decrease at trough. The numerous advantages summarized above make ABP monitoring an accepted method of BP measurement in hypertension therapy trials. Self-measurement of BP may be a valid and less expensive alternative to ABP monitoring.     

Spectral analysis of 24 h blood pressure monitoring in the assessment of trough: peak ratio. A randomized, placebo-controlled, cross-over comparison of ramipril and enalapril

BACKGROUND: The ratio between the magnitude of blood pressure reduction during the steady-state dosage interval (trough) and the maximum blood pressure reduction (peak) is an integrated in-vivo index both of the pharmacokinetic properties and of pharmacodynamic activity of an antihypertensive drug. Angiotensin converting enzyme inhibitors are often characterized by a low (often lower than 50%) trough: peak ratio but no direct drug comparisons are available. OBJECTIVE: To compare the absolute blood pressure reduction and the trough: peak ratio of daily doses of two angiotensin converting enzyme inhibitors, 5 mg ramipril and 10 mg enalapril. METHOD: After a 1-month wash-out and a 2-week placebo run-in, 25 mild hypertensives aged 47 +/- 4 years (17 men and eight women) were randomly assigned to treatments separated by a 2-week interval. Ambulatory blood pressure monitoring was performed and trough: peak ratio was calculated by the fast Fourier transform analysis of placebo-effect-subtracted data. RESULTS: After 1 month of ramipril treatment, 24 h blood pressure decreased from 139 +/- 10 to 129 +/- 11 mmHg for systolic (P < 0.05) and from 89 +/- 8 to 81 +/- 5 mmHg for diastolic blood pressure (P < 0.01). Also enalapril treatment caused a significant 24 h reduction in blood pressure both for systolic (to 132 +/- 7 mmHg, P < 0.05) and for diastolic blood pressure (to 84 +/- 5 mmHg, P < 0.05). Placebo caused a 24 h reduction in blood pressure (to 136 +/- 8 mmHg for systolic and 87 +/- 5 mmHg for diastolic blood pressure, NS, versus wash-out period). The two drugs were equally effective in reducing ambulatory blood pressure, but ramipril produced a trough: peak ratio significantly higher than that with enalapril both for systolic (48 +/- 11%, range 34-74%, versus 38 +/- 11%, range 21-67%, P < 0.005)and for diastolic blood pressure (47 +/- 11%, range 30-79 %, versus 37 +/- 12%, range 21-68%, P < 0.05). CONCLUSION: The low trough : peak ratios could have been due to the daily pattern of blood pressure of mild hypertensives, many of whom are normotensives at night-time, so that the main antihypertensive effect is exerted during daytime rather than during the night or early morning.     

Comparison of the AT1-receptor blocker, candesartan cilexetil, and the ACE inhibitor, lisinopril, in fixed combination with low dose hydrochlorothiazide in hypertensive patients

AIM: To compare candesartan cilexetil and lisinopril in fixed combination with hydrochlorothiazide with respect to antihypertensive efficacy and tolerability. METHODS: This was a double-blind (double-dummy), randomised, parallel group comparison in patients with a mean sitting diastolic blood pressure 95-115 mm Hg on prior antihypertensive monotherapy. Treatments were candesartan cilexetil/hydrochlorothiazide 8/12.5 mg once daily (n = 237) and lisinopril/hydrochlorothiazide 10/12.5 mg once daily (n = 116) for 26 weeks. The primary efficacy variable was change in trough sitting diastolic blood pressure. RESULTS: Changes in mean sitting diastolic blood pressure did not differ significantly between the groups (mean difference 0.5 mm Hg; 95% confidence interval -1.6, 2.7, P = 0.20). No significant differences between the groups was found for other haemodynamic variables (sitting systolic blood pressure, standing blood pressure, sitting/erect heart rate, and proportion of responders and controlled patients). Both drugs were well tolerated but the proportion of patients with at least one adverse event was significantly greater in the lisinopril group (80% vs 69%, P = 0.020). The proportion of patients spontaneously reporting cough (23.1% vs 4.6%) and discontinuing therapy due to adverse events (12.0% vs 5.9%) was also higher in the lisinopril group compared with the candesartan cilexetil group. CONCLUSIONS: The fixed combinations of candesartan cilexetil and hydrochlorothiazide 8/12.5 mg and lisinopril and hydrochlorothiazide 10/12.5 mg once daily are equally effective as antihypertensive agents. The fixed combination containing candesartan cilexetil is better tolerated than that containing lisinopril.     

Ambulatory blood pressure monitoring in clinical trials

Ambulatory blood pressure monitoring is increasingly being used in clinical trials. Trials with ambulatory monitoring, just like clinical experiments based on conventional sphygmomanometry, need to be controlled properly, because ambulatory blood pressure measurements are not completely devoid of placebo-like effects. The trough: peak ratio might be a useful instrument for assessment of the durations of action of antihypertensive drugs. However, its error term and confidence interval need to be reported and its determination in clinical trials requires further standardization. Ambulatory compared with conventional blood pressure measurements are characterized by a higher reproducibility. This property makes a reduction in sample size possible in cross-over but not in parallel group trials, if instead of the conventional blood pressure the 24 h or daytime blood pressures are compared. Trials focusing on the full course of the blood pressure through the day need a larger sample size than do those just concerning the conventional blood pressure level.     

Individual smoothing of blood pressure profiles to define responders or non-responders to drugs

OBJECTIVE: To compare different methods of individual therapyh efficacy assessment in order to define responding subjects. METHODS: Hypertensive patients were included in three double-blind clinical trials (placebo versus bisoprolol, lisinopril and amlodipine) and ambulatory blood pressure measurements (four per hour) were performed at the end of each month. We analysed the effect of therapy (placebo minus treatment) according to the following criteria: type of model (hourly mean, moving average, fast Fourier analysis), determination of the time to the peak effect (the lowest value of the modelled blood pressure) and the sampling time around this peak (1, 2,., 24 h). RESULTS: Regardless of the type of model, the level of individual therapy efficacy is significantly higher than that of the overall subjects (group efficiency), when the sampling time around this peak decreases. The proportion of responders decreases as the sampling time used to calculate the drop in blood pressure increases, whatever the kind of model and the threshold used to define responders (5 or 10 mmHg in systolic blood pressure). CONCLUSION: By this method, it is possible to appreciate the percentage of subjects considered individuallyas responders according to the time around the peak. This evaluation complements information given by the trough: peak ratio.     

Problems in the Evaluation of Antihypertensive Therapy Using the Trough/Peak Ratio

In 1988, the U.S. Food and Drug Administration proposed guidelines for the clinical evaluation of new antihypertensive drugs. According to these guidelines, the drug effect at trough (measured as the difference in blood pressure values from placebo) should be no less than one half to two thirds of the peak effect. Unfortunately, calculation of the trough/peak ratio suffers the consequences of many methodological, interpretative, practical, and epidemiological problems. When taking readings at short time intervals, noninvasive ambulatory blood pressure monitoring allows evaluation of blood pressure variability by means of several statistical parameters. Blood pressure variability, measured as the standard deviation of the overall 24-hour blood pressure measurements, has been demonstrated to be significantly correlated with target-organ damage in hypertensive patients. Blood pressure variability may not change with long-acting antihypertensive agents, but it may increase with short-acting ones. Therefore, assessment of the trough/peak ratio may be overcome by the evaluation of drug-induced changes in the standard deviation of the mean 24-hour blood pressure.     

动态血压监测评价甲磺酸氨氯地平的降压疗效

目的:应用动态血压监测(ABPM)评价甲磺酸氨氯地平的降压疗效,并与苯磺酸氨氯地平进行比较。方法:77例高血压患者按不同的治疗药物随机分为甲磺酸氨氯地平组、苯磺酸氨氯地平组,均治疗12周,治疗前后测定动态血压、心率、诊室血压、生化指标。结果:治疗12周末,2组的诊室血压,24h、白昼及夜间平均血压、平均脉压、血压负荷均显著降低(P<0·05或P<0·01),心率无显著改变。12周末甲磺酸氨氯地平组的总有效率在诊室血压为92·3%,在ABPM为71·8%;苯磺酸氨氯地平组分别为92·1%和68·4%,2组间均差异无统计学意义。甲磺酸氨氯地平组收缩压和舒张压的24h降压谷/峰比分别为70%和72%;苯磺酸氨氯地平组分别为66%和69%。2组患者出现的不良反应均轻微。结论:甲磺酸氨氯地平与苯磺酸氨氯地平一样能平稳、有效、安全地降低血压,可作为一线降压用药。     

Comparison of the effects on 24-h ambulatory blood pressure of valsartan and amlodipine, alone or in combination with a low-dose diuretic, in elderly patients with isolated systolic hypertension (Val-syst Study)

OBJECTIVE: The aim of this study was to compare the time-effect profiles of a once-daily administration of valsartan and amlodipine, each given alone or in combination with hydrochlorothiazide, in terms of ambulatory blood pressure (BP) and heart rate in elderly patients with isolated systolic hypertension. METHODS: One hundred and sixty-four elderly outpatients with systolic hypertension received valsartan 80 mg (n=79) or amlodipine 5 mg (n=85) once daily for eight weeks, after which the patients with poorly controlled office BP were up-titrated to valsartan 160 mg or amlodipine 10 mg once daily. If their office systolic BP was still >140 mmHg after eight weeks at these doses, 12.5 mg hydrochlorothiazide was added for a further eight weeks. The hourly BP decreases in all of the patients were calculated on the basis of 24-h ambulatory recordings made after the placebo period and at the end of active treatment. The trough/peak ratio and smoothness index were calculated in the responders. RESULTS: Both the valsartan- and amlodipine-based treatments effectively lowered mean 24-h, daytime and night-time systolic ambulatory BP (all p<0.001) without any significant differences between the two regimens. Ambulatory heart rate decreased in the subjects on valsartan and slightly increased in those on amlodipine (the differences in 24-h and daytime heart rate were significant (p=0.008 and 0.002 respectively). Among the 138 responders, the valsartan-based treatment had a greater anti-hypertensive effect during the daytime hours (p=0.02), a difference that was also significant for average 24-h BP (p=0.02). The mean systolic BP trough/peak ratio was 0.56 in the patients on valsartan, and 0.77 in those on amlodipine (NS). The smoothness index was respectively 1.70 and 1.58 (NS). CONCLUSIONS: The present results show that both the valsartan- and amlodipine-based treatments lead to a similar long-term reduction in 24-h systolic BP. However, in treatment responders, valsartan has a greater anti-hypertensive effect during the daytime.     

Aims of ambulatory blood pressure monitoring during phase II and III clinical trials

Ambulatory blood pressure monitoring (ABPM) is now widely used for the assessment of antihypertensive agents. This procedure may be used in phase II studies in dose-ranging evaluations. Indeed, ABPM provides data more appropriate for determining the dose-response relationship than are those from conventional blood pressure measurement. For each dose, it is possible to investigate both the magnitude and the duration of the antihypertensive effect. For these phase II studies, more accurate findings may be obtained by excluding patients for whom the diagnosis of hypertension is based on clinic readings only. ABPM tends to be used increasingly in clinical trials. An important advantage of this technique is to determine whether the complete dose interval is covered by the drug and to prove such a sustained duration of action in the natural environment of the patient. Because clinical decisions concerning management of hypertension are always based on office blood pressure measurement, entry criteria for these studies cannot derive from ABPM data but subgroup analyses may take ABPM data into account. The better intrasubject reproducibility of ABPM has been proposed to reduce the number of subjects needed for a clinical trial. This advantage seems to be more significant for cross-over studies. ABPM could reveal more easily than does conventional blood pressure measurement minimal differences in efficacy and duration of action between two different drugs. ABPM might help to quantify objectively the trough: peak effect ratio of an antihypertensive drug. Indeed, it allows better recognition of the real peak effect but the real-life conditions may be disadvantageous in calculating the ratio.     

动态血压监测评价复方厄贝沙坦的降压作用

目的：评价厄贝沙坦／氢氯噻嗪(复方厄贝沙坦，商品名安博诺)降压谷／峰比值及降压效果。方法：开放试验。28例轻中度高血压患者日服一次复方厄贝沙坦(厄贝沙坦150mg／氢氯噻嗪12、5mg)、共8周，治疗前后行24h动态血压监测。结果：收缩压、舒张压谷／峰比值分别为56．1％、55．3％，24h、昼、夜平均血压分别下降22．2／13．3mmHg、23．8／14．1mmHg、15．0／9．1mmHg。结论：复方厄贝沙坦日服一次，降压作用可维持24h。     

Through/Peak Ratios of Once Daily Angiotensin Converting Enzyme Inhibitors and Calcium Antagonists

Medications given once daily may increase compliance for treatment of hypertension, if the drugs have a prolonged duration of action. The time-effect profiles for antihypertensive drugs may not depend entirely on pharmacokinetic measurements (plasma levels). Thus, trough/peak effects on blood pressure should be measured. It has been suggested that trough/peak ratios be greater than 50% for optimal 24-h control of pressure. Because very little information is available for many angiotensin converting enzyme (ACE) inhibitors and calcium antagonists concerning their trough/peak ratios and awaiting prospective comparative trials with adequate methodology, we have analyzed the duration of action of blood pressure lowering during long-term therapy with commercially available ACE inhibitors and calcium antagonists in published studies that used ambulatory blood pressure monitoring. Published studies were searched in scientific databases using relevant key words. Twenty-four ACE inhibitor and 34 calcium antagonist studies with comparable methodologies were selected. The mean trough/peak ratios were computed after reconstruction of the curve of the magnitude of blood pressure changes against time. The results showed that once daily administration of ACE inhibitors produced on average ratios higher than 50% with fosinopril (64%), ramipril (50% to 63%), and trandolapril (50% to 100%). Other studied ACE inhibitors produced ratios on average equal to [enalapril (40% to 64%), cilazapril (10% to 80%), lisinopril (30% to 70%)] or significantly lower than 50% [captopril (25%), benazepril (40%), perindopril (35%), quinapril (10% to 40%), and moexipril (0% to 9%)]. As for once daily calcium antagonists, amlodipine (50% to 100%), lacidipine (40% to 100%), nifedipine Coat-Core (50% to 69%), nifedipine gastrointestinal therapeutic system (GITS) (60% to 94%), as well as various “slow release” formulations of diltiazem (20% to 80%) and verapamil (45% to 100%) had on average ratios higher than 50% whereas felodipine ER (30% to 45%), various slow release formulations of isradipine (10% to 80%), and nitrendipine (10% to 80%) had ratios lower than 50%. Although this retrospective literature analysis may have some theoretical limitations, it suggests that not all once daily ACE inhibitors and calcium antagonists cause trough/peak ratio superior to 50%. This may have important clinical implications. Am J Hypertens 1996;9:633–643.     

缬沙坦联合苯磺酸氨氯地平对女性高血压患者血压谷峰比值与平滑指数的影响

目的探讨在女性高血压患者中联用缬沙坦与苯磺酸氨氯地平对于控制血压谷峰比值及平滑指数的作用。方法对我院63例女性高血压患者进行随机分组,将单用苯磺酸氨氯地平、单用缬沙坦和联用两者治疗者各纳入A组、B组和C组,分析并评估3组病例的临床治疗情况。结果与治疗前相比,三组患者的24hSBP、24hDBP、dSBP、dDBP、nSBP和nDBP水平均显著下降（均为P〈0.05）。且除24hDBP之外,C组治疗后其余指标均要较A组和B组改善更明显（P〈0.05）。C组治疗后的血压谷峰比值与平滑指数均要较A组和B组高（P〈0.05）。结论为女性高血压患者提供缬沙坦与苯磺酸氨氯地平治疗有确切效果,对于控制患者血压谷峰比值、平滑指数有重要意义。     

Assessment of antihypertensive activity in the regulatory setting

Before a new antihypertensive drug receives regulatory approval, it must demonstrate a significant blood pressure-lowering effect over its entire dosing interval. The Food and Drug Administration recognizes several different methods for demonstrating antihypertensive activity, the gold standard continuing to be the office/casual blood pressure at the end of the dosing interval (trough). There should be at least two studies demonstrating a significant antihypertensive effect, at least one of which should include a placebo. Data obtained using ambulatory blood pressure monitoring are used for showing the time-course of the antihypertensive effect, particular attention being given to possible marked differences between the drug's maximum (peak) effect and its activity during the trough. In Europe, the Committee for Proprietary Medicinal Products also considers the office/casual blood pressure at trough to be a primary measure of outcome, responder rates using office/casual readings also being noted. The Committee recommends that data be obtained using ambulatory blood pressure monitoring in order to demonstrate a drug's antihypertensive activity. In addition, it specifically requests that a trough : peak ratio be calculated, whereas the Food and Drug Administration does not require this information.     

Vascular hypertrophy and albumin permeability in a rat model combining hypertension and diabetes mellitus: Effects of calcium antagonism,angiotensin converting enzyme inhibition,and angiotensin II-AT1-receptor blockade

The aim of this study was to compare the effects of angiotensin converting enzyme (ACE) inhibition, angiotensin II (AII) AT₁-receptor blockade, and dihydropyridine calcium antagonism on hypertrophy and on vascular albumin permeability in kidney, heart, and mesenteric artery in a model combining genetic hypertension and diabetes mellitus.Diabetes mellitus was induced by streptozotocin in 8-week-old spontaneously hypertensive rats. The animals were randomized to receive no treatment, the angiotensin converting enzyme inhibitor ramipril, the AII AT₁-receptor blocker valsartan, or the dihydropyridine calcium antagonist lacidipine for 3 weeks.Vascular albumin permeability was measured as the tissue content of intravenously injected Evans blue dye (EB) in kidney, heart, and mesenteric artery and the tissue/plasma EB ratio was calculated.Systolic blood pressure was reduced by all three antihypertensive regimens. Glycemic control was similar in all diabetic groups. Kidney hypertrophy was not affected by any of the antihypertensive drugs. Hypertrophy of the mesenteric artery was enhanced by lacidipine but was not affected by ramipril or valsartan. Relative heart weight was also increased by lacidipine. Vascular albumin permeability, expressed as EB content in micrograms/gram dry weight or as tissue/plasma EB ratio, was higher in the kidneys of lacidipine-treated rats than in any other group of diabetic rats, There was a positive correlation between kidney weight/body weight and kidney/plasma EB ratio in the diabetic rats.These findings indicate that the dihydropyridine calcium antagonist lacidipine is associated with an unfavorable effect on vascular hypertrophy and on vascular albumin permeability in the kidneys in rats with hypertension and diabetes mellitus. Furthermore, there seems to be a coupling in the diabetic kidney between hypertrophy and increased vascular albumin permeability.     

Methodological considerations in the evaluation of the duration of action of antihypertensive therapy using ambulatory blood pressure monitoring

We review the potential limitations of the two current methodologies for evaluating the duration of action of antihypertensive therapy: the smoothness index (SI) and the trough : peak ratio (TP). We propose a simple correction factor for the SI. The correction factor prevents the SI from reaching erroneous high values in situations in which the reduction in blood pressure (BP) is inadequate but very homogeneous. We refer to the corrected index as the SIn (normalized SI).