Enantioselective pharmacokinetics of the enantiomers of clevidipine following intravenous infusion of the racemate in essential hypertensive patients.

The aim of the study was to characterize the individual pharmacokinetics of (-)-R- and (+)-S-clevidipine following intravenous constant rate infusion of rac-clevidipine to essential hypertensive patients. Twenty patients received three out of five randomized treatments with clevidipine. The pharmacokinetics of the separate enantiomers were evaluated by compartmental analysis of blood concentrations vs. time curves using the population approach. The derived pharmacokinetic parameters were used to simulate the time for 50 and 90% postinfusion decline following various infusion times of rac-clevidipine. A two-compartment model was used to describe the dispositions of the enantiomers; there were only minor differences between the estimated pharmacokinetic parameters of the separate enantiomers. The mean blood clearance values of (-)-R- and (+)-S-clevidipine were 0.103 and 0.096 l/min/kg, and the corresponding volumes of distribution at steady state were 0.39 and 0.54 l/kg, respectively. The context-sensitive half-time was approximately 2 min regardless of stereochemical configuration, and a 90% decline in concentration was achieved approximately 8 min postinfusion for (-)-R-clevidipine and 11 min for (+)-S-clevidipine, following clinically relevant infusion times with clevidipine. In conclusion, both enantiomers are high-clearance compounds with similar blood clearance values. The volume of distribution for the enantiomers is slightly different, presumably due to differences in the protein binding. From a pharmacokinetic point of view, the use of a single enantiomer as an alternative to the racemic clevidipine will not offer any clinical advantages.

Organ damage in treated middle-aged hypertensives compared to normotensives: results from a cross-sectional study in general practice.

BACKGROUND: High blood pressure contributes to organ damage. However, during the past two decades there have been great advances in the medical treatment of hypertension. Technical progress has also made it easier to visualize organ damage. Hence we found it of interest to examine heart, brain and retina in a group of middle-aged treated hypertensives, comparing the results with those from a group of middle-aged normotensives. METHODS: The subjects were 40 (20 men) treated hypertensives and 40 (20 men) normotensives, who had previously taken part in a study in which ambulatory blood pressure monitoring had been performed. The heart was examined by echocardiography, the retina by photography and the brain by magnetic resonance imaging. RESULTS: Office blood pressure and 24-h systolic/diastolic blood pressure (S/D) were 141/86 (13/7) mmHg and 128/81 (11/6) mmHg in the hypertensives and 125/78 (10/8) mmHg and 118/74 (8/5) mmHg in the normotensives, respectively. Left ventricular mass was 101 (27) g/m2 in the hypertensives and 85 (18) g/m2 in the normotensives (p = 0.0025). The corresponding figures for the left atrium were 21.1 (3.1) mm/m2 in the hypertensives and 19.5 (2.2) mm/m2 in the normotensives (p < 0.001). E/A wave quotient was 1.09 (0.26) in the hypertensives and 1.26 (0.26) in the normotensives (p = 0.0045), while left ventricular systolic function did not differ between the groups. Ten hypertensives and one normotensive subject had left ventricular mass above normal range. Narrow retinal arteries were found in 22 hypertensives and 8 normotensives (p < 0.001). Brain magnetic resonance changes (deep white matter and/or periventricular) were found in 19 hypertensives and 9 normotensives (p = 0.0431). CONCLUSIONS: The hypertensives differed significantly from the normotensives concerning left ventricular mass, left atrium, left ventricular diastolic function and retinal vessel changes. Deep white matter and periventricular changes in the brain were also significantly different in the two groups. We can only speculate as to whether earlier antihypertensive treatment or further blood pressure reduction could have affected these differences.

A study of Tamm-Horsfall protein excretion in hypertensive patients and type 1 diabetic patients.

OBJECTIVE: The study was performed in order to evaluate to what extent hypertension or diabetes mellitus may affect the urinary excretion rate of Tamm-Horsfall protein. MATERIALS AND METHOD: The urinary excretion rates of albumin and Tamm-Horsfall protein, a measure of glomerular and distal tubular function, respectively were measured in patients with essential hypertension (n = 17) and in type 1 diabetes with (n = 20) or without nephropathy (n = 8) and in apparently healthy subjects (n = 10). RESULTS: Mean 24-h ambulatory blood pressure measurements showed higher blood pressure levels in the hypertensive (167/ 106 mmHg, p < 0.001) than in the diabetic patients with (136/84 mmHg) and without nephropathy (121/74 mmHg) and in healthy subjects (122/76 mmHg). Day and night ratios of systolic and diastolic blood pressure levels were not different among the four groups. Urinary albumin excretion rate was increased in patients with hypertension (30.8 x/ 3.4 microg/min; geometric mean x/tolerance factor; p < 0.001) and diabetes with nephropathy (462 x/ 3.5 microg/min; p < 0.001) compared with diabetic patients without nephropathy and healthy subjects (4.6 x/ 1.9 and 3.7 x/ 1.5 microg/min, respectively). The Tamm-Horsfall protein excretion rate was decreased in patients with diabetic nephropathy (11.6 x/ 3.5 microg/min) compared to patients with hypertension (36.3 x/2.1 1g/min; p < 0.01), diabetes without nephropathy (39.2 x/ 2.0 microg/min; p < 0.05) and healthy subjects (63.0 x/ 1.4 microg/min; p < 0.001), whereas no differences were found among the latter three groups. CONCLUSION: These data indicate that high blood pressure may be associated with albuminuria, while a decrease in excretion rate of Tamm-Horsfall protein may be associated with diabetic nephropathy. These associations need to be studied in a larger population.

A genetic polymorphism in connexin 37 as a prognostic marker for atherosclerotic plaque development.

BACKGROUND AND OBJECTIVES: Atherosclerosis is a multifactorial disease, in part characterized by chronic inflammatory changes in the vessel wall and loss of normal physical and biochemical interactions between endothelial cells and smooth muscle cells. Previous studies [Hu J., Cotgreave IA. J Clin Invest; 99: 1-5] have provided molecular links between inflammation and myoendothelial communication via gap junctions, suggesting that these structures may be important in the development of the atherosclerotic vessel phenotype. In order to strengthen this premise, the aim of the present work was to probe for structural polymorphisms in connexin 37, a gap junctional protein uniquely expressed in endothelial cells, and to assess for potential genotypic segregation in individuals displaying atherosclerotic plaque. METHODS AND RESULTS: Computer-based comparisons of Expressed Sequence Tags (ESTs) predicted a polymorphism in the human gap junctional protein connexin 37 (cx37). The C1019-T mutation results in a proline to serine shift at codon 319 (cx37*1-cx37*2). A Restriction Fragment Length Polymorphism (RFLP) assay, involving the insertion of a novel Drd I cleavage site in the proline variant revealed a statistically significant over-representation of the cx37*1 allele in association with atherosclerotic plaque-bearing individuals (Odds-ratio for the homozygote = 2.38, Chi2 = 7.693, P = 0.006), in comparison to individuals lacking plaque, irrespective of a history of hypertension. CONCLUSIONS: These data suggest that the C1019-T polymorphism in cx37 may provide 'single gene marker', which could be useful in assessing atherosclerotic plaque development, particularly in cardiovascular risk groups such as those with borderline hypertension.

Circulatory effects and pharmacology of clevidipine, a novel ultra short acting and vascular selective calcium antagonist, in hypertensive humans.

The pharmacokinetics of clevidipine, a potent short-acting vascular-selective calcium antagonist, was investigated during steady state and the postinfusion period in patients with mild to moderate hypertension. Furthermore, the dose-effect and blood concentration-effect relations and the tolerability of the drug were studied. Twenty patients were randomized to clevidipine intravenously at target dose rates of 0.18, 0.91, 2.74, and 5.48 microg/kg/min, respectively, or placebo. Each patient received in random order three infusion rates of clevidipine or placebo during three separate study days. Dose-dependent reduction in blood pressure and a modest increase in heart rate were noted. The extremely high clearance value and the small volume of distribution resulted in short half-lives of clevidipine, 2.2 and 16.8 min, respectively. The blood concentration and dose rate producing half the maximal effect (i.e. EC50 and ED50) were approximately 25 nM and 1.5 microg/kg/min, respectively. There was a linear relation between blood concentration and dose rate in the range studied. Clevidipine was safe and generally well tolerated; one patient was excluded because of adverse events at 2.74 microg/kg/min. In conclusion, clevidipine is a high-clearance calcium antagonist that may become a valuable contribution to the drugs used in conditions in which precise and rapid control of blood pressure is needed.

Long-term effects of diltiazem and atenolol on blood glucose, serum lipids, and serum urate in hypertensive patients. Swedish-Finnish Study Group.

UNLABELLED: The purpose of this long-term treatment study was to evaluate health-related quality of life by comparing the effects of diltiazem and atenolol on some important metabolic parameters. SUBJECTS, MATERIAL AND METHODS: In a Swedish-Finnish long-term multicenter study 256 patients with mild to moderate hypertension were randomized to treatment with diltiazem retard (D) (n = 127) or atenolol (A) (n = 129). Doses could be increased and additional captopril medication be given to achieve adequate blood pressure (BP) reduction. The treatment in group D lasted for two years while group A was treated for 1 year and then was given D for another 2 years. RESULTS: After 1 year BP was significantly reduced in both groups and to a similar degree. The BP reduction was maintained during the rest of the study. After 1 and 2 years, HDL had increased significantly (p < 0.001) in group D. There was a corresponding significant reduction of the LDL/HDL ratio. In group A there were no changes after 1 year regarding lipoprotein levels. After the switch to D, group A showed similar improvements regarding HDL and the LDL/HDL ratio as the original D group. CONCLUSION: It is concluded that D and A are equally effective in lowering BP. However, long-term treatment with D, but not with A, has a favorable effect on HDL concentrations and the LDL/HDL ratio. According to these findings D affects the risk factor profile in hypertension.

Neuropeptide Y and hypertension.

Neuropeptide Y is a cotransmitter in the sympathetic nervous system with potent contractile effects on blood vessels. The plasma levels of neuropeptide Y-like immunoreactivity in patients with severe hypertension (> 120 mmHg) were increased compared with the levels in control subjects and were still elevated after long-term pharmacologic treatment of normotension. Neuropeptide Y stimulated DNA synthesis, total cell number, and total protein production in human vascular smooth muscle cells through a Y1-receptor. A Gi/G(o)-coupled second messenger mechanism seems to be involved, because pretreatment with pertussis toxin abolished the mitogenic effect. Neuropeptide Y potentiated the mitogenic effect of noradrenaline, and together with adenosine 5'-triphosphate, the sympathetic cotransmitters reached a mitogenic effect of approximately 20% of fetal calf serum. We have shown that neuropeptide Y, noradrenaline, and adenosine 5'-triphosphate, apart from their effects on vascular tone, are stimulators of vascular smooth muscle cell growth. The receptors that mediate the mitogenic effect have been examined. The circulating plasma levels are increased in patients with severe hypertension. These findings indicate that the sympathetic cotransmitter neuropeptide Y may be of importance in sympathetic vascular regulation and involved in pathophysiologic conditions.

End-organ damage in treated severe hypertension: close relation to nocturnal blood pressure.

In an attempt to improve therapeutic decision-making in severe hypertension, different blood pressures (BP) were correlated with target organ damage in a cross-sectional study of 20 asymptomatic patients. Casual BP was 197/117 (s.d. 31/10) mmHg despite therapy. Each subject was assigned an end-organ score on the basis of the number of silent cerebrovascular damages detected by magnetic resonance imaging, funduscopic retinopathy, cardiac hypertrophy by echocardiography, and renal involvement evaluated by isotopic renography. The pooled scores for target organ damage showed significant correlations with an elevated asleep mean ambulatory (amb-) brachial systolic (r = 0.84) and diastolic BP (r = 0.88) but not with either awake amb-BP (means or peak values), causal BP or invasive radial BP at the clinic. Night-time amb-DBP increased with age in contrast to the daytime DBPs. Furthermore, the nocturnal fall in mean arterial amb-BP was significantly less in patients aged > or = 60 years, average 5%, than in patients < 60 years, 16%. This may have prognostic implications even if, after age adjustment, the inverse relation (r = -0.78) between the end-organ scores and the dip in BP did not reach independent significance. The close association of cardiovascular complications with night-time rather than daytime BP emphasises the importance of making a prospective study in this field, trying to optimise the nocturnal BP in severe hypertension.

Efficacy and tolerability of felodipine ER and diltiazem SR as monotherapy in primary hypertension: a double-blind randomized study.

PURPOSE: Efficacy, tolerability, and optimal doses of felodipine ER (FER) and diltiazem SR (DSR), given as monotherapy, were evaluated in patients with mild or moderate primary hypertension. METHODS: This was a multicenter, double-blind, parallel-group study of 98 hypertensive patients. Following a 4 weeks placebo run-in period, patients were randomized to either FER 5 mg once daily (qd) or DSR 90 mg twice daily (bid). If supine DBP was > 90 mmHg after 2 and 4 weeks treatment, the dose was increased to 10 mg FER qd or 120 mg DSR bid plus 20 mg FER qd or 180 mg DSR bid, respectively. The double-blind treatment lasted 8 weeks. RESULTS: After 8 weeks FER treatment 70% of the patients responded (DBP < or = 90 mmHg or DBP decrease > or = 10 mmHg) and 50% became normotensive (DBP < or = 90 mmHg); the corresponding figures for DSR were 63% and 37%, respectively. No statistical significant differences in BP reduction and HR were found between the two compounds. HR did not change during the study. Seven patients discontinued due to adverse events (AEs). Five patients received FER and two patients received DSR. The AEs were similar in the two groups and generally mild. CONCLUSIONS: At the highest dose levels of FER and DSR, no further BP reduction was observed, but there was a tendency to report more AEs. Both FER and DSR can be used as first-line therapy in hypertension.

Direct and indirect blood pressure in normotensive and hypertensive subjects.

OBJECTIVES: To compare intrabrachial blood pressure (I-BP) with simultaneously measured contralateral auscultatory (A-)BP in hypertensive and normotensive subjects. The question was whether differences between direct and indirect BP are influenced by the BP levels. SUBJECTS: Hypertensive subjects treated with either placebo (n = 10) or metoprolol (n = 8) and age-matched normotensive subjects (n = 15), selected from a defined patient population waiting for cholecystectomy or hernia repair. Measurements were performed pre-induction of anaesthesia. RESULTS: In the hypertensive subjects, cuff systolic BP (SBP) was lower than I-BP by an average of 8 mmHg (placebo-) and 7 mmHg (metoprolol-treated), whereas diastolic A-BP (A-DBP) was 3 and 7 mmHg higher, respectively. In the normotensive subjects, mean A-SBP and I-SBP agreed closely, whereas A-DBP was 11 mmHg higher. Thus, SBP differences (i.e. indirect-direct BP) were significantly less and DBP differences significantly greater in the normotensive than in the hypertensive subjects (P < 0.05). Plasma renin activity and adrenalin showed better correlations with A-MBP than with I-MBP. CONCLUSIONS: The drift of cuff systolic readings fell progressively below the intrabrachial values when BP increased, whilst diastolic cuff values approached the direct pressures. Since A-MBP did not significantly differ from I-MBP in any group, one must ask whether hypertension would be more correctly defined according to MBP criteria.

Office and ambulatory blood pressure in patients with craniomandibular disorders.

To assess the physiologic response to daily life stress in patients with craniomandibular disorders (CMD), office and ambulatory blood pressure and heart rate were studied in 25 female patients and 25 controls. Significant differences (p < 0.05) were found between the groups for heart rate before the clinical examination and that in the patient group when compared before and after the clinical examination. Higher values were found for mean daytime systolic and diastolic blood pressure in the control group compared with the patient group (p < 0.05). The mean number of systolic blood pressure > or = 140 mmHg during 24 h and daytime was significantly higher (p < 0.05) in the control group than in the patient group. In this study the CMD patients with muscular diagnosis were not more stressed than healthy subjects in the daily activities as evaluated by ambulatory blood pressure measurements.

Cerebral blood flow in patients with severe hypertension, and acute and chronic effects of felodipine.

OBJECTIVES: To evaluate whether a spontaneous increase in cerebral blood flow (CBF) could be observed in subjects with severe hypertension and to study the effect of a calcium antagonist, felodipine, on blood pressure and CBF after acute and chronic administration. DESIGN: Patients with severe hypertension were recruited at the emergency ward. Patients with previous treatment with calcium antagonists, women of child-bearing potential, severe uraemia, nephrotic syndrome, heart failure, manifest cerebrovascular lesions and pathological liver function tests were excluded. METHODS: CBF was measured by single-photon emission computed tomography after intravenous administration of xenon-133 before (CBF1) and after intravenous infusion of felodipine, 0.01 mg/min during 40-60 min (CBF2) in 12 patients aged 25-67 years with no antihypertensive treatment except for beta-blockers in four patients and beta-blockers plus a diuretic in one patient. CBF was repeated after 3 weeks of oral therapy with felodipine, 5-10 mg twice a day with the addition of beta-blockers in 10/12 patients (CBF3). RESULTS: During the felodipine infusion blood pressure decreased. There were no neurological symptoms or signs before or during the felodipine administration. CBF1 was within normal limits with no significant differences between previously treated and untreated patients. There was a non-significant tendency to increase in global CBF after felodipine administration, associated with a significant reduction in the physiological side differences in blood flow. CONCLUSIONS: In spite of the initially very high blood pressure, no general or focal hyperaemia was observed, and thus no evidence for a 'breakthrough' of the cerebral autoregulation. Felodipine gives a smooth blood pressure reduction with a maintained CBF.

Sensory nerve terminal activity in severe hypertension as reflected by circulating calcitonin gene-related peptide (CGRP) and substance P.

In patients with severe hypertension and in age and sex matched controls the circulating levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and substance P-LI were measured. Samples were taken before medication, after 2-4 weeks and 2-12 months of pharmacological treatment to normotension. In the control group CGRP-LI levels were significantly higher for females than for males. No such relation was seen for substance P-LI. There were no correlations between CGRP-LI, substance P-LI or blood pressure. In the untreated acute hypertensive group there was a significant correlation between circulating levels of CGRP-LI and both diastolic and systolic blood pressure. No such relationship was seen for substance P-LI. The plasma levels of substance P-LI were significantly elevated (2.8 +/- 4.0) compared to controls (1.3 +/- 1.3, pmol/l, mean +/- S.D., p < 0.01). The levels of CGRP-LI did not differ from the control group. After 2-4 weeks of treatment the blood pressure decreased significantly and the plasma levels of substance P-LI were normalized while the CGRP-LI still did not differ from that of controls. After 2-12 months of treatment the blood pressure was still normalized, and the plasma levels of CGRP-LI and substance P-LI were not different from the control group. In the present study there was a positive correlation in hypertensives between the circulating CGRP-LI levels and diastolic and systolic blood pressure and elevated levels of substance P-LI. This would implicate the existence of a dynamic control through which the sensory system may register and damp the pressure response.

Usefulness of self-measured blood pressure when diagnosing mild hypertension.

Blood pressure (BP) measured by the patients themselves at home and at their workplaces (self BP) and office blood pressure (office BP) were compared with ambulatory BP (amb BP) in 41 middle-aged borderline hypertensive men when diagnosing hypertension. Ambulatory BP was used as the 'gold standard'. The mean (standard deviation) value for office BP was 142/89 (14/7), self BP 143/92 (14/8), and amb BP 134/88 (12/6) mmHg. There was no difference between diastolic office BP and self BP as instruments for diagnosing hypertension. Furthermore, combining the two added little to the diagnostic value obtained from only one of them.

Neuropeptide Y-like immunoreactivity and hypertension.

OBJECTIVE: Neuropeptide Y is a co-transmitter with noradrenaline in sympathetic neurons supplying arteries and veins with potent contractile effects. To investigate the role of neuropeptide Y in hypertension, we measured the circulating levels of neuropeptide Y and noradrenaline in patients with severe hypertension. DESIGN: Samples were collected from patients with untreated, severe hypertension (diastolic blood pressure > 120 mmHg) and in age- and sex-matched controls. After treatment with beta-adrenoceptor blockers, diuretics, angiotensin converting enzyme inhibitors of calcium antagonists, samples were taken from the patients during 12 months. METHODS: The circulating levels of neuropeptide Y-like immunoreactivity (NPY-LI) were measured with a radioimmunoassay using a rabbit antiserum. Catecholamines were measured using high-performance liquid chromatography and electrochemical detection. RESULTS: There was a significantly higher level of NPY-LI in the patients when they were compared with the controls. However, there was no correlation either in the controls or in the hypertensives between systolic blood pressure, diastolic blood pressure and NPY-LI or noradrenaline. The increased level of NPY-LI in plasma remained elevated for up to 12 months despite reduction in blood pressure to acceptable levels. The noradrenaline level was not increased before treatment, after 2-4 weeks or after 2-12 months treatment. CONCLUSION: The high level of NPY-LI may represent a marker for higher activity of the sympathetic nervous system which is not controlled by the treatment of blood pressure to normotension.

Comparison between enalapril and lisinopril in mild-moderate hypertension: a comprehensive model for evaluation of drug efficacy.

UNLABELLED: The objective of this study was to compare enalapril with lisinopril in terms of blood pressure control at rest, during dynamic exercise test, during isometric exercise test, and during 24 h--with special focus on blood pressure control during the morning hours, 18-24 h post-dose. Furthermore, we compared ACE activity in serum before and after 4 weeks of drug treatment. A four-week double-blind, randomized parallel group study compared enalapril 20 mg o.d. with lisinopril 20 mg o.d. preceded by a 4-week single blind run-in period on placebo. Fifty-eight patients (49 males and 9 females, mean age 50.9) were recruited and 56 completed the study. Blood pressures at randomization were 161/108 and 164/106 for the enalapril and the lisinopril subjects, respectively. Echo: LVPWd 9.5 (normal range 6-12 mm) and IVSd 10.3 mm (normal range 6-12 mm). STATISTICS: ANCOVA. Enalapril and lisinopril were equally effective in lowering blood pressure at rest, during dynamic and isometric exercise as well as during 24 h. The attained blood pressure levels during the early morning hours were for enalapril treatment 119/76 and 121/76 mmHg for lisinopril treatment. The ACE activity in serum 24 h post-dose was lower (p < 0.001) after treatment with lisinopril 8.0 (SD 3.3) mumol/min/1 than with enalapril 16.1 (SD 6.0). The corresponding values for placebo were 18.8 (SD 4.6) and 17.8 (SD 5.7). No difference was found in blood pressure lowering efficacy between enalapril and lisinopril even though the blood pressure changes were evaluated in a more comprehensive way than in earlier studies of these drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma atrial natriuretic peptide (ANP) in relation to blood pressure in severe hypertension.

Atrial natriuretic peptide-like immunoreactivity in plasma (ANP-LI) was studied in patients with severe hypertension (n = 21) and in matched healthy control subjects. There was no correlation between ANP-LI and blood pressure, and the distribution of ANP-LI values did not differ between the two groups. These results are consistent with the assumption that an increase in ANP is not caused by elevated blood pressure, although elevated ANP-LI may be found in subgroups of hypertensive subjects with increased atrial pressures due to, for example, cardiac failure.

Hand-free stethoscope--method and instrument for more reliable blood pressure measurements.

Measurement of blood pressure is subject to two sources of variation: biological and measurement variation. It is important to bear in mind that the ability to interpret the Korotkoff sounds correctly determines the levels of both systolic and diastolic blood pressure. To improve the ability to distinguish between the Korotkoff phases, the handfree stethoscope and the hand-free method were developed. The improved stethoscope head was fixed under the edge of the cuff, thus reducing the noise generated from physiological tremor and other movements. This resulted in more distinct Korotkoff sounds. Furthermore, the new method reduced the spreading of blood pressure values. In 107 patients the average systolic blood pressure recording was 3.1 mmHg higher and the average diastolic blood pressure was 3.5 mmHg lower. We conclude that the new stethoscope and technique provide a means of significantly improving the indirect measurement of blood pressure.

Antihypertensive efficacy and tolerability of enalapril and slow-release verapamil in essential hypertension: a double-blind, cross-over study.

The antihypertensive efficacy and tolerability of enalapril (E) and slow-release verapamil (V) were compared in a 2-month double-blind cross-over study in 22 patients with mild to moderate essential hypertension. After 1 month, significantly lower systolic (P less than 0.01) and diastolic (P less than 0.02) blood pressures (BP) were achieved with E, 20 mg d-1, compared with V, 240 mg d-1. After 2 months of treatment, BP reductions were similar after E, 40 mg d-1, and V, 240 mg twice a day. The fall in supine mean BP after 2 months of treatment with V was significantly greater in patients aged greater than or equal to 50 years of age (P = 0.02) (median 18 mmHg) than in patients aged less than 50 years (10 mmHg). E showed similar effectiveness in both age groups. Statistical group analysis of a quality-of-life questionnaire showed no significant differences between the active drugs and the placebo. It is concluded that E and V are equally effective as antihypertensive agents, and that both drugs are well tolerated.