Relaxation therapy for hypertension. Comparison of effects with concomitant placebo, diuretic, and beta-blocker

We compared the effects of relaxation therapy in hypertensive patients taking placebo, a beta-blocker (atenolol, 100 mg/d), or a diuretic (chlorthalidone, 50 mg/d), and we also compared the effects of relaxation therapy with the effects of the latter two drugs alone. Blood pressures were measured not only in the relaxation therapists' office and at a hypertension clinic, but also in the patient's environment by means of 24-hour ambulatory blood pressure recordings. The effect of relaxation therapy, while statistically significant, was modest. There was no generalization of effect to ambulatory blood pressure. Atenolol was significantly more effective than relaxation in reducing both systolic and diastolic pressure. Chlorthalidone was significantly more effective than relaxation in reducing systolic but not diastolic pressure in the hypertension clinic only. The long-term effects of relaxation were independent of concomitant drug use, but within the actual relaxation sessions blood pressure dropped further during chlorthalidone than during placebo or atenolol treatment.     

Treatment of hypertension in mild asthmatic patients with atenolol

Fourteen patients with uncomplicated essential hypertension and mild asthma were treated with Atenolol 50-125 mg/day for up to 8 months. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), rate pressure index (RPI), stress testing time (STT) and peak expiratory flow rate (PEFR) were measured before, during and after stress testing (ST) before and during treatment. Atenolol significantly lowered HR, SBP, DBP and RPI. It prolonged STT and had no effect on PEFR. Furthermore, Atenolol did not worsen the patient's asthma except for one patient. The drug did not interfere with the bronchodilatation effect of salbutamol. Atenolol can be used cautiously to treat hypertension in asthmatic patients under certain conditions.     

Effects of atenolol and diltiazem-SR on exercise and pressure load in hypertensive patients

The effects of monotherapy with atenolol or diltiazem-SR on blood pressure, 24-h blood pressure (BP) load, and exercise capacity were tested in patients with mild to moderate (stages I and II) essential hypertension. After 3-week single blind placebo therapy, patients with sitting diastolic blood pressure (SDBP) of 94-114 mmHg were randomized to atenolol 50 mg/day (62 patients) or diltiazem-SR 90 mg b.i.d. (60 patients) in a double-blind parallel study. Depending on SDBP response, the dose was increased to 100 mg/day for atenolol and 180 mg b.i.d. for diltiazem-SR. Twenty-four-hour ambulatory blood pressure measurements and exercise tolerance lest by the Bruce protocol were done at the end of placebo and active treatment. Compared with placebo, both atenolol and diltiazem-SR significantly decreased heart rate (HR), sitting systolic blood pressure (SSBP), SDBP, ambulatory BP, BP load for waking and sleeping hours, area under the BP curve, rate-pressure product (p < 0.001), and exercise time (NS). Atenolol exerted a greater effect on ambulatory BP, HR, rate-pressure product, waking diastolic BP load, and area under the 24-h BP curve. The drugs were well tolerated and caused no serious side effects necessitating discontinuation of treatment. These findings indicate that (1) monotherapy for hypertension with atenolol or diltiazem SR is effective and well tolerated, (2) it decreases the 24-h BP load, (3) it does not interfere with exercise capacity.     

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.     

Comparison of atenolol with propranolol in the treatment of angina pectoris with special reference to once daily administration of atenolol.

Fourteen patients with angina pectoris completed a double blind trial of atenolol 25 mg, 50 mg, and 100 mg twice daily and propranolol 80 mg thrice daily. In comparison with placebo, all active treatments significantly reduced anginal attacks, consumption of glyceryl trinitrate, resting and exercise heart rate, resting and exercise systolic blood pressure, and significantly prolonged exercise time. There was no significant difference between the effects of propranolol and atenolol. Nine patients completed a further trial comparing atenolol given once or twice daily. Both regimens were effective and there was no significant difference between the reductions in anginal attacks, glyceryl trinitrate consumption, systolic blood pressure, or heart rate. Twenty-four-hour ambulatory electrocardiograms showed that atenolol consistently reduced heart rate throughout the 24-hour period whether given once or twice daily. Atenolol is a potent antianginal agent which, in most patients, is likely to be effective once daily.     

动态血压监测方法评价比索洛尔及阿替洛尔的降压疗效

对４０例原发性高血压患者采用２４小时动态血压监测方法对β受体阻滞剂（比索洛尔、阿替洛尔）进行降压疗效的比较。结果显示：２种药物均能达到全天的降压疗效；比索洛尔２４小时对收缩压及舒张压的降压作用强于阿替洛尔；比索洛尔２４小时中对舒张压降低的百分率明显强于收缩压，并能在夜间保持持续降压状态；２种药物对心率的降低无差异性。这提示，比索洛尔的降压疗效（２４小时１次口服）优于阿替洛尔。     

A double blind comparison of perindopril and atenolol in essential hypertension

A multicentre randomised double-blind trial was performed in order to compare the therapeutic efficacy and acceptability of the angiotensin converting enzyme (ACE) inhibitor perindopril with those of atenolol in mild to moderate hypertension. After one month of placebo, 173 patients with supine diastolic blood pressure (DBP) between 95 and 125 mmHg were randomised to receive perindopril 4 mg once daily or atenolol 50 mg once daily. Monthly assessments were made for three months. Treatment was adjusted at these visits if supine DBP was greater than 90 mmHg; the dose was first doubled (8 mg perindopril or 100 mg atenolol once daily) and then hydrochlorothiazide was added. The pretreatment blood pressure levels were similar in both groups. Supine DBP was 105.5 +/- 0.9 mmHg (n = 85) in the perindopril group and 106.9 +/- 0.9 mmHg (n = 88) in the atenolol group. At the end of the third month, the study target blood pressure (supine DBP less than or equal to 90 mmHg) was achieved in a significantly (P = 0.006) larger percentage of patients in the perindopril group (78%) than in the atenolol group (58%). This appeared to be due to a greater potentiation of the antihypertensive effect by the addition of diuretic to perindopril than to atenolol. The fall in systolic blood pressure was significantly greater in the perindopril group than in the atenolol group (supine: 26.5 +/- 2.0 mmHg vs. 20.6 +/- 2.0 mmHg; P = 0.042) although the fall in DBP was comparable (supine: perindopril 17.4 +/- 0.9 mmHg, atenolol 15.6 +/- 1.1 mmHg; P = 0.195).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of nitrendipine and atenolol on blood pressure and intracellular sodium in hypertensive blacks

Thirty-five hypertensive black patients were randomized in a double-blind fashion to receive either atenolol 100 mg per day (n = 17) or nitrendipine 20 mg daily (n = 18) for six weeks. Atenolol and nitrendipine significantly reduced blood pressure (P less than 0.05 or less). However, the magnitude of the decrease in supine systolic blood pressure (SBP) and diastolic blood pressure (DBP), and in standing diastolic pressure was more pronounced (P less than 0.05 or less) in the nitrendipine than in the atenolol group. Neither of the drugs significantly affected the erythrocyte sodium and potassium concentrations or the ouabain-sensitive efflux of sodium. In multiple regression analysis the changes in supine SBP and DBP with nitrendipine were independently and negatively correlated with the patients' age and initial blood pressure, and positively with the change in supine pulse rate; the change in supine SBP was also negatively correlated with initial erythrocyte sodium concentration. Our results suggest that nitrendipine is more efficient than atenolol in hypertensive blacks and that besides older age and higher pre-treatment. BP levels, a higher intracellular sodium concentration could predict a greater response to nitrendipine.     

Weighted Fourier analysis of blood pressure curves after lisinopril versus atenolol administration in young hypertensives

OBJECTIVE: To evaluate and compare the effects of lisinopril versus atenolol administration on the diurnal blood pressure profile and the nocturnal blood pressure fall in young mild-to-moderate essential hypertensives.METHODS: Thirty patients were studied. After a 2-week placebo run-in period, they were single-blind randomly assigned to receive 20 mg lisinopril or 100 mg atenolol. Using a SpaceLabs 90207 device, their ambulatory blood pressure was measured before and after 12 weeks of therapy. The readings were analysed using Fourer series with four harmonics. RESULTS: Lisinopril and atenolol administration significantly decreased office and ambulatory blood pressure values compared with the placebo period. The daily blood pressure curves obtained from Fourier analysis showed that the circadian rhythm was not altered by lisinopril and atenolol administration. From the night:day ratio for the nocturnal blood pressure fall, we found that atenolol administration minimized the average night-time blood pressure dip by increasing the number of non-dippers. In contrast, lisinopril administration did not modify the day-night difference, preserving the nocturnal blood pressure fall. CONCLUSION: Lisinopril and atenolol administration as a first-step treatment of young essential hypertensives produced comparable degrees of diurnal control of arterial pressure. The blood pressure fall at night in patients treated with atenolol was slightly less than that found with lisinopril treatment.     

The prolonged antihypertensive effect of once daily atenolol: a study of continuous non-invasive arterial blood pressure monitoring

This study was carried out on 12 hospitalized hypertensive patientsto assess the antihypertensive efficiency and the duration ofaction of a once daily dose of atenolol. 100 mg of atenolol was given at 8 am every day for 5 days. Beforeand during the therapeutic period, 24-h blood pressure recordingswere obtained with a continuous, automatic, non-invasive methodworking on the principle of oscillometry (Dinamap 845.950).Atenolol induced a significant reduction in mean blood pressurefrom 119±3.6 to 102.3±4.7 (P<0.001). This effectwas significant from the very first day of treatment and wasmaintained over the duration of the study in ten patients. Thedecrease in blood pressure induced by atenolol lasted 24 h.Clinical tolerance of atenolol was excellent. In particularno case of excessive bradycardia was noted.     

A new approach to assessing antihypertensive therapy: effect of treatment on pulse pressure. Candesartan cilexetil in Hypertension Ambulatory Measurement of Blood Pressure (CHAMP) Study Investigators

BACKGROUND: A high pulse pressure is an independent cardiovascular risk factor. It has therefore been suggested that antihypertensive treatment should not only reduce systolic blood pressure (SBP) and diastolic blood pressure (DBP), but should also decrease pulse pressure (SBP minus DBP). In a previous analysis, we showed that two angiotensin II type 1 (AT1)-receptor blockers, candesartan cilexetil and losartan, differed in their effects in reducing SBP and DBP. OBJECTIVE: To compare the efficacy of candesartan cilexetil and losartan according to a new approach--their effect on pulse pressure--and to describe the dose-effect relationship for SBP, DBP and pulse pressure, in a placebo-controlled study. METHODS: After a 4-week placebo run-in period, 268 patients with mild-to-moderate hypertension were allocated randomly to groups to receive placebo, candesartan cilexetil (8 mg once daily) or losartan (50 mg once daily), for 4 weeks. The doses were then doubled to 16 and 100 mg, respectively, for the final 4 weeks of the study. Clinic blood pressure was measured 24 and 48 h after each dose of drug or placebo, and ambulatory blood pressure was monitored from 0 to 36 h after each dose, at baseline and after 4 and 8 weeks of treatment. RESULTS: Candesartan cilexetil decreased ambulatory pulse pressure significantly (P < 0.05) more than did losartan during both daytime and night-time, and over the 24 h period after the previous dose. A different dose-effect relationship on SBP, DBP and pulse pressure was observed. The duration of action of candesartan cilexetil was greater than that of losartan. After a missed dose (i.e. approximately 24-36 h after the previous dose), mean ambulatory pulse pressure values after 4 and 8 weeks of treatment with candesartan cilexetil were lower than those observed with losartan (P < 0.005). Clinic pulse pressure measurements were consistent with these ambulatory measurements. CONCLUSIONS: AT1 -receptor blockers differ both in their ability to reduce pulse pressure and in their duration of effect, candesartan cilexetil having a greater and more sustained effect than losartan. Different dose-effect relationships on SBP, DBP or pulse pressure were observed. Further prospective studies based on pulse pressure are needed to analyse the mechanism of reduction of pulse pressure and to determine its prognostic value.     

Hemodynamic and metabolic responses to valsartan and atenolol in obese hypertensive patients

OBJECTIVE: None of the current hypertension guidelines provides specific guidance regarding pharmacological management of obese hypertensive patients. Treatment recommendations for lean hypertensives may not be simply extrapolated to obese hypertensive persons. DESIGN: Randomized, double-blind, parallel-group study with a 13-week treatment period. SETTING: Multicenter study in Germany. PATIENTS: Obese patients with mild to moderate uncomplicated essential hypertension. INTERVENTION: Patients were treated with valsartan at a maximal dose of 160 mg/day or with atenolol at a maximal dose of 100 mg/day. Hydrochlorothiazide at doses of 12.5-25 mg was added in patients with blood pressure > 140/90 mmHg on monotherapy. MAIN OUTCOME MEASURES: Blood pressure, lipid and glucose metabolism, and highly sensitive C-reactive protein (hsCRP) were monitored. RESULTS: Sixty-seven patients were randomized to valsartan and 65 patients to atenolol. With valsartan, systolic blood pressure (SBP) decreased from 160.8 +/- 8.9 to 140.5 +/- 13.3 mmHg and diastolic blood pressure (DBP) from 96.1 +/- 7.0 to 85.1 +/- 8.1 mmHg by the end of the study. With atenolol, SBP decreased from 159.3 +/- 6.8 to 139.8 +/- 14.5 mmHg and DBP from 95.0 +/- 6.8 to 83.5 +/- 7.5 mmHg (P = 0.91 for SBP and P = 0.34 for DBP between interventions). Body weight did not change with either treatment. We did not see a significant difference in the response of lipid levels or hsCRP between interventions. To assess the cumulative effect of each intervention on glucose metabolism over the trial duration, we calculated individual areas under the curve for homeostasis model assessment for insulin resistance (HOMA-IR) over time. The resulting area under the curve was significantly smaller with valsartan compared with atenolol (P = 0.02). CONCLUSIONS: Beta-adrenoreceptor blockers and AT1-receptor blockers, particularly in combination with low-dose diuretics, effectively lower blood pressure in obese hypertensives. However, metabolic responses differ between both treatment strategies, with beneficial effects of AT1-receptor blockers. AT1-receptor blockers are a good choice in obese hypertensives, given the profoundly increased diabetes risk in this population.     

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.     

The antihypertensive effect of atenolol and bopindolol in the elderly

The antihypertensive efficacy and tolerability of two betablockers: atenolol and bopindolol, was compared in a group of 30 elderly subjects aged 64.8 +/- 4.6 years. The daily dose of the two agents was relatively low. Atenolol 50-100 mg and bopindolol 0.5-1.0 mg sufficed to cause reduction of DBP to the target of less than or equal to 95 mm Hg, when applied as monotherapy. This was achieved in 75% of cases with bopindolol and in 93% of cases with atenolol. Atenolol, 50-100 mg/dd, lowered blood pressure from 173.7 +/- 13.2/103.7 +/- 3.0 (weekly) to 155.5 +/- 16.5/86.5 +/- 8.2 mm Hg (week 12) (P less than 0.005) while bopindolol, 0.5-1.0 mg, lowered blood pressure from 171.6 +/- 11.3/104.1 +/- 3.6 to 158.7 +/- 20.9/86.1 +/- 6.0 mm Hg (P less than 0.005). Heart rate was reduced from 80.5 (week 4) to 66.7 +/- 7.3 (week 12) by atenolol (P less than 0.0001), and from 83.7 +/- 11.8 (week 4) to 71.1 +/- 7.5 (week 12) by bopindolol (P less than 0.0001). Between treatment differences: comparisons yielded P values which were not sufficiently low to reject the null hypothesis of no difference between the two treatments. Well-being and short-term memory were not affected by either agent and tolerability of both drugs was good. These findings demonstrate that both bopindolol and atenolol are useful agents for control of hypertension in the elderly.     

Exercise stress test in young hypertensive patients. Response to vasodilators (prazosin) vs. beta-blocker (atenolol) agents

Dynamic response of arterial blood pressure during exercise has been studied in 40 normotensive young subjects and 20 mild hypertensive young patients (20-40 years of age). Hypertensive patients were treated with atenolol (beta blocker) and prazosin (vasodilator). Both groups underwent maximal exercise stress test. A double-blind nonrandomized study was practiced in hypertensive patients with placebo, prazosin (3 mg/12 h), and atenolol (100 mg/24 h). Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and exercise duration (ED) were analyzed. All parameters remained stable in both groups. The hypertensive patients showed an increase in maximum SBP more than 230 mmHg during the placebo phase. This same group showed a significant increase in HR at rest two hours after administration of prazosin. Atenolol produced a significant reduction in HR both during rest and exercise. Both drugs produced a significant decrease in SBP and DBP (at rest and exercise). We conclude that exercise test is a noninvasive procedure that could distinguish mild arterial hypertension. The dynamic changes of arterial blood pressure can be controlled with prazosin (3 mg/12 h) or 1 daily intake of 100 mg atenolol.     

Ambulatory pressure monitoring in the assessment of antihypertensive therapy

A low-cost, ambulatory blood-pressure monitor has been calibrated and validated against a random zero sphygmomanometer. The repeatability of ambulatory pressure recordings after a placebo month in 44 mild to moderate untreated hypertensives was assessed. Systolic blood pressure showed a mean difference over 1 month of 2.0 mmHg, with a standard deviation of differences of 9.3 mmHg. The diastolic blood pressure mean difference was 0.1 mmHg (SD=6.3 mmHg). This variability was much less than for clinic readings (SD=17.3 mmHg) or for single home pressure readings (SD=19.7 mmHg). Using ambulatory monitoring to detect a drop in pressure of 8/5 mmHg with a power of 0.9, the number of subjects needed in a parallel group trial is reduced from 360 to 68, and in a crossover study from 88 to 16 subjects. The usefulness of ambulatory pressure monitoring is demon-strated in a placebo-controlled comparisom of atenolol, nifedipine retard, or their combination in random order. Eleven subjects, 21–60 years, with initial average blood pressures of 166.5/104.7 mmHg, showed a reduction in pressure with atenolol 50 mg a day of 15.1/10.0 mmHg, with nifedipine retard 20 mg b.i.d. of 21.0/11.6 mmHg, and with atenolol 50 mg and nifedipine retard 20 mg once a day of 26.2/16.8 mmHg. Ambulatory monitoring of pressure improved the accuracy of the trial and demonstrated a reduction in the alerting response with atenolol.     

Effects of losartan and atenolol on left ventricular mass and neurohormonal profile in patients with essential hypertension and left ventricular hypertrophy

OBJECTIVE: To compare the effects of the angiotensin II antagonist, losartan, with those of atenolol on left ventricular hypertrophy (LVH), blood pressure and neurohormone concentrations in hypertensive patients with LVH. DESIGN: A multinational, randomized, double-blind trial. SETTING: Hospital. PATIENTS: Hypertensive patients with an echocardiographically documented left ventricular mass index (LVMI) 120 g/m(2) (men) or 105 g/m(2) (women). INTERVENTIONS: Patients allocated randomly to groups received either losartan or atenolol 50 mg/day for 36 weeks, with possible titration to 100 mg/day, and addition of hydrochlorothiazide 12.5 or 25 mg/day. MAIN OUTCOME MEASURES: Changes in LVMI and sitting systolic (SBP) and diastolic (DBP) blood pressures after 36 weeks of treatment (study powered for non-inferiority hypothesis). All echocardiographic data were read in a central laboratory by staff blinded to the treatments and sequence of echocardiographic tapes. RESULTS: The estimated treatment difference between the losartan and atenolol regimens (mean change from baseline at week 36) in LVMI was -2.5 g/m(2) [95% confidence interval (CI) -7.36 to 2.37 g/m(2) ] in favor of losartan, indicating that losartan was significantly non-inferior ( 0.001, non-inferiority limit 8 g/m(2) ) and numerically superior to atenolol in reducing LVMI. The losartan-based regimen significantly reduced LVMI after 36 weeks compared with baseline (-6.56 g/m(2) , 95% CI -10.24 to -2.88 g/m(2) , P<0.001), whereas the atenolol-based regimen had no significant effect (-3.71 g/m, 95% CI -7.75 to 0.32 g/m(2) , P= NS). In a subset of 82 patients, significant changes in serum concentrations of atrial natriuretic peptide, brain natriuretic peptide and immunoreactive amino-terminal pro-brain natriuretic peptide were recorded in losartan-treated ( 0.01) but not atenolol-treated patients. Losartan and atenolol significantly decreased SBP and DBP from baseline after 6, 12, 24 and 36 weeks. The changes from baseline in DBP were greater in the atenolol group at weeks 6 and 36 [difference -2.6 mmHg ( P= 0.016) at week 36]. However, both treatment regimens achieved similar SBP/DBP values at week 36 (141.1 +/- 12.8/86.8 +/- 8.2 mmHg for losartan and 141.4 +/- 17.2/85.0 +/- 10.1 mmHg for atenolol, respectively). Overall, losartan treatment was associated with significantly fewer drug-related clinical adverse events, compared with atenolol (10 and 22%, respectively, P= 0.028). CONCLUSIONS: Both losartan- and atenolol-based regimens effectively decreased blood pressure. Losartan was non-inferior and numerically superior to atenolol in regression of LVH. The reduction in hypertrophy with losartan treatment was accompanied by reductions in circulating concentrations of cardiac natriuretic peptides. Losartan, by specifically blocking angiotensin II, may therefore have effects on the heart beyond those expected from the decrease in blood pressure alone. Losartan was better tolerated than atenolol.     

Effects of nebivolol and atenolol on insulin sensitivity and haemodynamics in hypertensive patients

OBJECTIVES: To compare the effects of nebivolol and atenolol in 25 ambulatory hypertensive patients with impaired glucose tolerance. DESIGN: Clinic and ambulatory blood pressure, insulin sensitivity (euglycemic-hyperinsulinemic clamp), glucose tolerance (intravenous glucose tolerance test), systemic and regional haemodynamics were measured after 4 weeks of placebo and after each 16-week treatment period in a double-blind, crossover fashion. RESULTS: Nebivolol and atenolol similarly reduced (P< 0.001) clinic and ambulatory blood pressure by approximately 15/10 mmHg, systolic and diastolic. Clinic and ambulatory heart rate was reduced to a greater extent (P < 0.01) by atenolol than nebivolol. Atenolol was associated with an approximately 20% reduction in insulin sensitivity (insulin-induced glucose disposal rate/mean insulin concentration ratio, P < 0.01) and an approximately 10% reduction in glucose disappearance rate (K-value, P < 0.05), whereas these variables were not significantly modified with nebivolol. Cardiac output was reduced similarly (P < 0.05) by both drugs at rest but forearm blood flow, forearm vascular resistance or total peripheral resistance were unaffected. A significant inverse correlation coefficient between cardiac output and insulin sensitivity was found at baseline, suggesting that a compensatory increase in systemic blood flow occurs in hypertensive patients with progressively more marked insulin resistance. This relationship was unaffected by nebivolol but was lost with atenolol. CONCLUSIONS: These results indicate that insulin sensitivity was not modified significantly by nebivolol, whereas it was reduced by atenolol, although blood pressure was decreased to the same extent by both drugs. Neither drug induced systemic or forearm vasodilatation but the inverse relationship between cardiac output and insulin sensitivity was preserved with nebivolol but not with atenolol.     

Comparative pharmacoclinical study of 2 beta-blockers: atenolol and betaxolol in slight-to-moderate arterial hypertension

Sixteen patients with mild to moderate hypertension were randomized to receive either atenolol 100 mg a day (group A: 2 females, 6 males, mean age 42.3 years) or betaxolol 20 mg a day (group B: 8 males, mean age 49.3 years), both drugs given once daily for one month with a wash out on the 5th day. Pretreatment blood pressure was significantly higher in group B than in group A: this disparity, linked with randomization, hampered the comparison of the antihypertensive efficacy of both drugs but not the comparison of their pharmacodynamics. The maximal effect on resting supine blood pressure occurred later with betaxolol (4th day) than with atenolol (1st day), while the effect on peak exercise-blood pressure and heart rate was rapidly maximal (1st day) for both beta-blockers. The duration of the antihypertensive action at rest seemed to be nearly similar, while the effects of betaxolol on exercising heart rate and blood pressure were more prolonged than those of atenolol: on the wash out day, plasma atenolol and betaxolol levels fell in a same way but the increase in peak systolic blood pressure was more marked in group A than in group B, so that the positive correlation we found between the plasma drug levels and the percentage of peak systolic blood pressure reduction, was much closer with atenolol (p less than 0.001) than with betaxolol (p less than 0.05).     

Little Effect of Ordinary Antihypertensive Therapy on Nocturnal High Blood Pressure in Patients with Sleep Disordered Breathing

The antihypertensive effects of four different antihypertensive medications (β-blocking agent, atenolol 50 mg; calcium-antagonist, isradipine SRO [slow release] 2.5 mg; diuretic, hydrochlorothiazide [HCTZ] 25 mg; and angiotension converting enzyme-inhibitor, spirapril 6 mg) on obese patients with sleep disordered breathing and hypertension were compared by the ambulatory blood pressure measurement (ABPM).Eighteen patients were randomized in a double-blind, crossover fashion to receive each of the four different medications for 8 weeks. ABPM was performed at baseline and after an 8-week treatment with these medications. A 2- to 3-week washout period occurred both at baseline and between each of the four medications. Three patients were omitted from statistical analysis because of technical problems of ABPM.Atenolol, isradipine SRO, and spirapril decreased significantly (P < .01) the mean 24-h systolic blood pressure, whereas HCTZ did not. The mean 24-h diastolic blood pressure decreased significantly after all four medications: 12 (SD ± 14) mm Hg with atenolol, 7 (SD ± 10) mm Hg with isradipine SRO, 3 mm Hg (SD ± 14) with HCTZ, and 6 (SD ± 15) mm Hg with spirapril (P < .01). During nighttime none of the medications reduced the mean diastolic or systolic blood pressure significantly. According to the 24-h blood pressure curve the influence of these four medications during the whole measurement period was not similar. Atenolol and spirapril lost their antihypertensive effect during the early morning hours. The antihypertensive effect of HCTZ varied markedly from hour to hour. The trough-to-peak ratio of no medication was >0.50.Negative correlation was observed between the apnea time and the mean systolic 24-h (r = −0.604, P = NS) and the mean systolic nocturnal blood pressure change (r = −0.590, P = NS).Our study revealed that the daytime high blood pressure was quite easily controlled by the ordinary monotherapy in these patients with partial upper airway obstruction and hypertension. Instead none of the medications used decreased nocturnal high blood pressure markedly.