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Betablockers reduce mortality by 30% after a myocardial infarction. The anti anginal effects of betablockers are also very well established. They improve survival after a non cardiac surgery in patients at high cardiovascular risk. Atenolol should nevertheless be avoided for primary cardiovascular protection in patients with hypertension older than 55 yrs. This may not apply to more selective betablockers, or betablockers with vasodilator effects. We also now have another bradycardic agent, ivabradine, which may prove very useful in heart failure patients who cannot tolerate a betablocker.

We report a 53-year-old woman with hyperkaliemia secondary to treatment with atenolol. The diagnosis of atenolol induced hyperkaliemia was obtained after excluding other causes of hyperkaliemia and normalization of potassium serum level following the discontinuation of this medication without any other modification (treatment or diet). Furthermore, when atenolol was again introduced, serum potassium level increased and normalized when atenol was definitively discontinued. The mechanism of hyperkaliemia we suspected is probably a reduction of potassium intracellular transfer.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

To evaluate the anaesthesiologists' attitude concerning the perioperative administration of betablockers (BB), especially prophylactic BB, in order to prevent postoperative cardiac complications.A questionnaire including 20 items was sent to 700 anaesthesiologists of 4 French departments (Ain, Isere, Loire et Rhone).The response rate was 30%. Eighty-eight percent of respondents prescribed the BB with the premedication, on the day of the surgery in patients who were on regular BB. Before major surgery, 37% percent of respondents always or usually introduced prophylactic BB in patients with high cardiac risk. Atenolol was the drug of choice for 68% of perioperative BB users. Seventy-one percent of anaesthesiologists using prophylactic BB asked for a cardiologic opinion before starting BB therapy.In practice, anaesthesiologists continued BB during the perioperative period in patients who were on chronic treatment with BB. However, prophylactic perioperative administration of BB in patients with high cardiac risk is still inadequate and dependent on a cardiologic opinion.

A randomised double-blind comparison of three treatment strategies in 533 patients with mild-to-moderate hypertension over 6-9 months. The low-dose perindopril/indapamide (PER/IND) combination (2 mg and 0.625 mg, respectively) daily resulted in a significantly better blood pressure control and systolic blood pressure decrease. In addition, the low-dose PER/IND combination showed superior efficacy/safety criteria than the sequential strategy of atenolol (50 mg) then losartan (50 mg) then amlodipine (5 mg), and the step-by-step strategy of valsartan (40 mg then 80 mg then 80 mg plus hydrochlorothiazide 12.5 mg).

Systolic blood pressure (SBP) and systolic-diastolic pulse pressure (PP) may be superior predictors of cardiovascular risk than diastolic blood pressure (DBP). Treatments that selectively reduce SBP and PP may therefore be of particular interest. The REASON project was a randomised, double-blind study comparing the very low-dose combination perindopril 2mg/indapamide 0.625 mg (Per/Ind) versus atenolol 50mg for 12 months in 471 hypertensive patients. Both treatments produced similar reductions in brachial DBP, but Per/Ind produced greater reductions than atenolol in SBP (-23.1 +/- 15.6mm Hg vs -16.2 +/- 16.0mm Hg; p0.001) and PP (-9.9 +/- 12.4mm Hg vs -3.3 +/- 13.5mm Hg; p0.001). Patients with echocardiographic left ventricular hypertrophy at baseline (n = 124) showed greater reduction of left ventricular mass index with Per/Ind (-11.3 +/- 15.4 g/m(2)) than atenolol (-5.3 +/- 15.1 g/m(2); p = 0.031). Relative to atenolol, Per/Ind selectively targets SBP and PP, which could be important in reducing cardiovascular risk.

The purpose of this study is to evaluate the short-term benefit of a beta-blocker (atenolol) on clinical and echocardiographic parameters of patients presenting isolated or predominant mitral stenosis in sinus rhythm. It is a prospective study performed on 26 patients who have had a clinical and echocardiographic assessment before and 15 days after treatment by atenolol. After 15 days of beta-blocker treatment, there is a significant improvement of dyspnea (57.6% in class III or IV before beta-blockade versus 15.3% with atenolol; P = 0.001) and a significant decrease of the heart rate (83.3 +/- 15.2 versus 68.9 +/- 13.9; P = 0.001) and the diastolic blood pressure (8 mmHg +/- 1.3 versus 7.2 mmHg +/- 0.9; P = 0.01). The Doppler echocardiography shows a significant increase of the stroke volume calculated by the Doppler method (28.7 +/- 6.2 versus 38.6 +/- 9.7 mL; P = 0.04). There is an insignificant trend to an improvement of the left ventricular systolic function, an increase of cardiac output and the decrease of the mean transmitral gradient. The factors associated with the failure of beta-blocker treatment are: the right heart failure (P = 0.04) and the low diastolic blood pressure (P = 0.01). The beta-blockers could be a logical and effective treatment of patients with mitral stenosis waiting for balloon commissurotomy or surgery.

The extended use of interventional surgery of revascularisation has modified the prognosis and the evolution of ischaemic heart diseases. However, both coronary artery bypass graft and percutaneous transluminal coronary angioplasty failed to make the symptomatic or subclinical ischaemic manifestations of chronic coronary insufficiency disappear. The interest of using betablockers as a first-line therapy was widely demonstrated. However, their combination with another efficient molecule is often necessary. The aim of this trial has been to appreciate the efficiency of the association of a betablocker with either trimetazidine or with isosorbide monoitrate. Hundred and eighty five patients retaining a positive effort test despite 100 mg of atenolol, received in addition, either 60 mg of trimetazidine (93 cases) of 60 mg of isosorbide mononitrate (92 cases) for a two-month period and are then re-evaluated at the end of this period. The ischaemic threshold is delayed in a significant way in both groups (p0.0001; trimetazidine +7%, isosorbide mononitrate +10.7%). Twenty-three percent of the exercise tests under trimetzidine and 19% under isosorbide mononitrate become negative after two months of the therapeutic combination. The clinical improvement is even clearer with the disappearance of the angina crisis during the week before the second exercise test in 63% of the cases under trimetazidine and 54% of the cases under isosorbide mononitrate, among the patients who had kept it under atenolol at the inclusion. In conclusion, the combination of a second efficient molecule, trimetazidine or isosorbide mononitrate, brings a functional and objective improvement to patients with insufficient chronic coronary disease not totally controlled using a betablocker, even with high dosage. One should notice two important advantages in favour of the trimetazidine: one is practical due to a better tolerance (lack of cephalalgia), the other is conceptual (use of the complementary metabolic approach of cellular oxygenation rather than the haemodynamic approach of nitrate compounds which are already in concurrency with all other anti-ischaemic molecules).

In hypertension, consideration of systolic blood pressure (SBP) and pulse pressure (PP) is now well recognized from epidemiological and therapeutical points of view, after numerous years of interest in only diastolic blood pressure. SBP, and also PP, are tightly linked to mechanical properties of large arteries. It is now possible to investigate precisely, with very good repeatability, these mechanic properties. The REASON study is an international multicenter randomised, controlled, parallel-groups study in essential hypertensives. The very low dose perindopril/indapamide combination (Per/Ind: 2 mg/0.625 mg) was compared with atenolol (50 mg) for a 12-month active treatment period in terms of blood pressure reduction efficiency and change in large artery hemodynamics to attempt to relate changes in pressure and changes in arterial mechanics. 471 patients suffering from hypertension were included, 406 benefitted from the treatment for one year (per-protocol analysis) and 96 benefitted from arterial investigations (pulse wave velocity and aortic wave reflection with applanation tonometry). Changes in brachial and central SBP and PP were higher with Per/ind than with atenolol. The reduction in pulse wave velocity was similar with both drugs, but aortic wave reflections were more reduced with Per/Ind than with atenolol. The very low dose perindopril/indapamide decreases SBP and PP to a larger extent than does a betablocker after a 12-month treatment. Changes in arterial mechanics, non invasively measured, were the same (pulse wave velocity) or in favour of Per/Ind vs atenolol (higher reduction in aortic wave reflection, with higher reductions in central systolic and pulse pressures).

The LIFE study ("Losartan Intervention For Endpoint reduction in hypertension study") demonstrated a significant cardiovascular protection by an angiotensin AT1 receptor antagonist, losartan, in hypertensive patients with left ventricular hypertrophy. At similar blood pressure control, losartan, as compared to atenolol, reduced the relative risk of primary cardiovascular event (death, myocardial infarction, or stroke) by 13% (p = 0.021) in the whole cohort of 9.193 patients after a mean follow-up of 4.7 years. In a subgroup of 1.195 diabetic patients, the protection was even more marked with a reduction of the combined risk of 24% (p = 0.031) and a fall of the mortality of 39% (p = 0.002). In conclusion, losartan prevents cardiovascular morbidity and death more effectively than atenolol, and seems to confer benefits beyond reduction in blood pressure.

The assessment of results of medical treatment, angioplasty and coronary bypass surgery in diabetic coronary patients is difficult because of the absence of distinction in the subgroups of type 1 and 2 diabetes and of stable and unstable angina. With respect to medical therapy, betablockers are practically without deleterious effects and are effective in diabetic populations. The same is true of other antianginal drugs. Conventional coronary angioplasty is associated with poorer results than the general population in the long-term, partly because of progression of the coronary artery disease and partly because of an increased incidence of restenosis. The use of stents improves these results, which are similar to those of the general population with single vessel disease or those without proteinuria. Coronary bypass surgery, despite a certain perioperative morbidity, is associated with an identical survival rate at 5 years as non-diabetics, providing the internal mammary artery is grafted. The comparison between these methods is resumed in the ACIP study which opposes the 3 strategies, in Morris et al's study comparing medical and surgical approaches and, finally, in the recent BARI trial where patients were randomly allocated to angioplasty or surgery. It would appear that the surgical strategy gives better results in multivessel disease. However, many reserves have been voiced because of the small numbers of patients, the high number of excluded patients and the fact that recent progress in angioplasty with widespread use of stenting associated with the prescription of new antiaggregant drugs was not taken into account.

Circadian variations of the QT interval and its heart rate dependency have been established. However, the respective roles of the sympathetic and parasympathetic nervous systems in their regulation are still undetermined. Eighteen healthy volunteers (average age 39 +/- 7 years, 10 men) were recruited and selected randomly to receive either placebo or atenolol (100 mg/day). The treatments were crossed after 7 days. The rate dependency of the QT was assessed by day and by night by 24 hour Holter ECG monitoring. The effects of atenolol on the rate dependency of the QT interval depend on the time of day. During the daytime, the QT rate dependency was reduced by atenolol (0.180 (0.162:0.198) versus 0.216 (0.195:0.236) with placebo, p0.01) whereas during the night, the QT rate dependency was the same in both groups. Therefore, the betablocker is associated with an inversion of the daily modulation of the QT rate dependency. The daytime rate-dependency of the QT interval in decreased with betablocker therapy. This result suggests a direct or indirect influence of the sympathetic nervous system on the rate dependency of ventricular repolarisation.

The authors report an original case of the association of three pathologies: pheochromocytoma, hyperthyroidism and cardiomyopathy with left ventricular outflow tract obstruction. This type of cardiac disease has occasionally been described in cases of pheochromocytoma and are usually induced by the endocrine disturbance because they regress with treatment of the pheochromocytoma. The associated hyperthyroidism observed in this case is very rare and may have increased the left ventricular pressure gradient. Medical treatment before surgery of the pheochromocytoma was unusual in that a triple therapy was used including betablockers, classically contra-indicated in pheochromocytoma alone. In this case, it provided excellent control of the blood pressure and decreased the left ventricular obstruction during the perioperative period.

When used as first-line treatment, any monotherapy selected from one of the main classes of agents for the management of slight to moderate arterial hypertension cannot be expected to have a success rate exceeding 60%. However, this level of efficacy approaches 80% if two classes of antihypertensive drugs with complementary modes of action are combined--a notable example being the combination of a beta-blocker, atenolol 50 mg, and a calcium antagonist, sustained-release nifedipine 20 mg. This fixed combination provides efficacy and tolerability in the treatment of arterial hypertension. Atenolol has beta-adrenolytic properties similar to those of propranolol, the most commonly named comparator drug. Atenolol is a selective beta 1-adrenergic antagonist with negative chronotropic, bathmotropic, dromotropic and inotropic actions. Because of its selectivity, it induces only moderate vasoconstriction. Its cardioselective nature diminishes the risk of bronchospasm, an event commonly induced by this type of drug. Atenolol reduces renin secretion from the renin-angiotensin system and consequently decreases the production of angiotensin II and plasma aldosterone. The renal effects of atenolol are an increase in both diuresis and natriuresis, with a reduction in the renal plasma flow. beta-Adrenergic antagonists in general modify carbohydrate metabolism and may mask the precursor signs of hypoglycaemia. They have a negligible effect upon lipid metabolism and practically no effect on total or high density lipoprotein cholesterol levels. Nifedipine belongs to the class of dihydropyridines. It acts by blocking the influx of calcium ions through the slow channels. Although a potent vasodilating agent, nifedipine does not induce tachycardia or water-sodium retention. The negative inotropic effect observed in vitro has not been reported in humans; the coronary dilatation produced by nifedipine is indisputable, both in unstable angina and exertional or exercise-induced angina. However, its cardioprotective effect remains questionable outside the context of recent-onset atheromatous plaques. Nifedipine increases renal blood flow and is practically devoid of diabetes-inducing factors. The fixed combination of atenolol 50 mg and sustained release nifedipine 20 mg offers a particularly interesting complementary action, the beta-blocker reducing the dihydropyridine-induced activation of the sympathetic nervous system and the latter reducing the vasoconstriction induced by the beta-blocker. Compared with each agent used alone, the pharmacokinetic profiles of atenolol and nifedipine remain unmodified by their administration in the fixed combination.

During recent decades, undeniable progress has been made with regard to the management of arterial hypertension. Larger numbers of patients are aware they have hypertension, receive treatment and benefit from this therapy. Furthermore, significant reductions have been observed in morbidity and mortality resulting from cardiovascular diseases. The objectives of hypertension treatment have been formulated on the basis of results of extensive epidemiological studies. Only a few patients receiving monotherapy actually achieve and maintain acceptable blood pressure levels. The complex pathogenesis of essential hypertension, the implications of nervous and humoral counter-regulatory effects, the heterogeneous character of individual responses to any given class of antihypertensive treatment and the onset of adverse effects all account for these failures. The search for a simple, effective and well-tolerated treatment based on a low dose combination of 2 classes of antihypertensive agents is consequently legitimate. The fixed combination of atenolol 50 mg and sustained release nifedipine 20 mg enables patients to benefit from the antihypertensive synergy of a beta-blocker and a calcium antagonist (dihydropyridine). Several open-ended or double-blind, controlled studies have shown that this combination produces a more marked antihypertensive effect than the individual components used alone or other reference monotherapies. Furthermore, it has been shown that this effect persists throughout the entire 24-hour period; this has been confirmed by 24-hour blood pressure monitoring. Short and medium term tolerability is significantly improved: the side effects commonly associated with the 2 drugs when used alone are reduced with the combination formulation since the 2 active substances have different and complementary mechanisms of action. In addition, long term studies have shown that therapeutic efficacy and tolerability remain stable and have even been seen to improve over a 12-month period. The fixed combination of atenolol-nifedipine has a role in strategies for the treatment of mild to moderate hypertension, particularly under the following conditions: when first-line monotherapy has failed to attain specific clearly defined objectives, including stabilised blood pressure levels together with acceptable tolerability. when patient compliance is jeopardised as a result of undesirable side effects. when the vascular burden is aggravated through lack of attention to individual risk factors in hypertensive patients. In more serious forms of hypertension, the atenolol-nifedipine combination can replace sequential monotherapies or other combination treatments that have failed to comply with the various criteria of therapeutic efficacy. Controlling arterial hypertension commonly requires polytherapy with 3 or even 4 different drugs in conjunction with particularly strict rules governing hygiene and diet. The addition of the fixed combination of atenolol-nifedipine simplifies the treatment of patients with arterial hypertension by limiting the daily doses and reducing laboratory monitoring.

We report a case of acute respiratory distress syndrome (RDS) in a patient treated with Atenolol (Tenormin) for two months. According to the different criteria which are generally used, the diagnosis of pulmonary oedema induced by Atenolol was made. There were extra pulmonary clinical signs (cutaneous and articular) which were associated with blood hypereosinophilia and were suggesting the mechanism of RDS was hypersensitivity.

Determination of optical isomers is based on some molecule properties to have one or more chiral asymmetrical carbon center. Enantiomers can be resolved by high performance liquid chromatography (HPLC) with a chiral mobile phase additive, by change into diastereoisomers by derivatization or by separation on chiral column. We retained the last technique for the separation of seven beta-blockers (atenolol, alprenolol, labetalol, nadolol, oxprenolol, pindolol and propranolol) using an alpha 1-AGP column. Results indicate that the mobile phase was specific to each beta-blocker. The wavelength chosen was lambda = 225 nm and the flow rate was 0.9 ml/min. A part from that, determinations of isomers of propranolol and atenolol in different fluids biologicals were also achieved.

A randomized double-blind trial was conducted in hypertensive subjects with hypercholesterolemia treated with pravastatin in order to compare the effects of captopril and atenolol on lipid metabolism.After a pre-inclusion period, 147 eligible subjects (64 men and 83 women, age range 32-74 years) were randomized into two groups and given, in a double-blind trial, either captopril (50 mg/d) or atenolol (50 mg/d) for 6 months. The controlled trial was followed by an open trial in 120 subjects for 6 more months. Laboratory tests for lipid metabolism were performed at inclusion and at 6 months.Control of blood pressure was satisfactory and similar in the two groups. Lipid tests were performed both in local and a centralized laboratory with good interlaboratory correlations. High density lipoprotein (HDL)-cholesterol remained unchanged in the captopril group declined slightly in the atenolol group. Total cholesterol increased moderately in both groups. Triglycerides increased somewhat in the captopril group and significantly more in the atenolol group. These results were maintained during the open trial. Most of the undesirable effects were benign and did not require treatment.The effects of captopril and of atenolol are not diminished in combination regimens with pravastatin. The antihypertensive efficacy was similar for the two treatments, but the effect on lipid metabolism was more favorable with captopril.

Seventeen male untreated mild essential hypertensive patients with a mean age of 41 years agreed to participate in a double-blind randomized trial to test the effects of treatment with cilazapril, an inhibitor of angiotensin I converting enzyme, in comparison to treatment with atenolol, a beta-blocker, on the structure and function of subcutaneous resistance arteries. Patients were randomized to receive either cilazapril 2.5-5 mg or atenolol 25-100 mg per day per day. Blood pressure before treatment was 147/99 and 148/99 mmHg in both groups respectively. At 1 year of treatment blood pressure was 132/86 and 131/85 mmHg in both groups of patients respectively. Treatment for one year with cilazapril resulted in a reduction in the media/lumen ratio of resistance arteries (150-400 microns lumen diameter) dissected from subcutaneous gluteal biopsies from 7.5 +/- 0.3% before treatment to 6.3 +/- 0.2% 1 year later (p0.05), still slightly but significantly larger (p0.05) than the media/lumen ratio of resistance arteries of normotensive controls (5.1 +/- 0.3%). In arteries from patients treated with atenolol there was no significant change with treatment (8.0 +/- 0.6% before and 8.1 +/- 0.5% after 1 year of treatment). Active wall tension responses to endothelin-1 were blunted in hypertensive patients and normalized in the cilazapril-treated patients, but were unchanged in those taking atenolol. Relaxation in response to acetylcholine of norepinephrine pre-contracted arteries was still significantly reduced after one year (0.05) in comparison to those of normotensive patients in the patients treated with atenolol, whereas they were not in those who had received cilazapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Placebo has only a slight effect on ambulatory blood pressure (ABP). Some authors have suggested that the use of a placebo is not necessary in a study on the drugs effect on ABP. We demonstrate that even if placebo effect is small, the use of a placebo group is still necessary. Effects of one daily dose of 50 mg atenolol + 20 mg slow-released nifedipine (AN) were investigated. Patients with office DBP 90-110 mmHg received, in a double-blind protocol, either AN (group AN, n = 31) or a placebo (group P, n = 26). Ambulatory BP (ABP) and HR were measured (Spacelabs or Diasys systems) for 24 h before and one month after treatment. The 2 groups were comparable before treatment. After 1 month under treatment, ABP was significantly lower in the AN group, compared to the P group, and this over the whole day (p = 0.03 to p0.0001). The effect was the most important between 10-17 h (p0.0001). HR was significantly lower in the AN group during daytime (6-22 h), but not during the night (22-6 h). Over the whole group, placebo effect was not significant. However, ABP did decrease under placebo in subjects with high initial pressure. As a result, an analysis without data from the placebo group led to an overestimation of the effects of the drug.

SHEP (Systolic Hypertension in the Elderly Program) is a multicenter controlled therapeutic trial which included 4,736 subjects aged 60 years and over, who had isolated systolic hypertension at three consecutive visits at the outpatient clinic. The treatment, based on low doses of diuretic (chlorthalidone 12.5-25 mg daily) combined, when necessary, with a cardioselective beta-blocker (atenolol 25 to 50 mg daily), significantly reduced the incidence of cerebrovascular and coronary events; the relative risk reduction for total mortality was not statistically significant. The beneficial cardiovascular effects were observed in both sexes, and in the 80+ age group. These results show that this particular therapy applied to this form of hypertension decreases the risk of both coronary and cerebral events, as was already suggested by the meta-analysis of the controlled therapeutic trials performed with diuretics, beta-blockers and other older antihypertensive drugs in patients with permanent diastolic hypertension. They also show the limitations of this therapeutic strategy, which controlled only 50 percent of the patients who were, however, highly selected, especially concerning the absence of associated morbid conditions and treatments. The need for, and feasibility of, new controlled therapeutic trials comparing the mortality and morbidity associated with various new antihypertensive therapies must now be discussed.

The antihypertensive efficacy of combination therapy with N-E-A was evaluated during 6 months in 15 patients with hypertension associated with mild to moderate kidney failure. After 6 months a significant reduction of SBP and DBP (p0.001), with improvement of creatinine clearance and with no adverse effects on ECG, heart rate and routine laboratory tests test, was observed in 3 patients treated with N 20 mg x 2/d + E 10 mg/d + A 50 mg/d and in 8 patients treated with N 20 mg x 3 + E 10 mg x 2, + A 50 mg x 2. Four patients did not respond to this therapy.

Five beta-blocking agents are effective as long-term prophylactic treatment of migraine: propranolol, metoprolol, timolol, atenolol and nadolol. Propranolol has been most extensively studied and proved effective in 19 of 21 controlled trials. The optimal dose should be determined on a case-by-case basis, by increasing the daily dosage gradually. Among the properties of beta-blockers, the only one which appears to be correlated--albeit negatively--with effectiveness on migraine is intrinsic sympathomimetic activity (ISA): drugs without ISA are effective against migraine whereas partial agonists are not. The mode of action of beta-blockers in migraine is still poorly understood; one of the most cogent current hypotheses involves reduction of brain catecholaminergic hyperactivity.

Although diuretics and beta-blockers are efficient in treating high blood pressure and in decreasing the occurrence of strokes, these therapeutics have deleterious effects concerning lipidic metabolism, therefore worsening another cardiovascular risk factor. A comparative study evaluates the effects of prazosin and atenolol on plasmatic lipids of hypertensive patients. The results of this study confirm that prazosin can avoid an increase in plasmatic lipids. This therapy could therefore be prescribed to improve the ratio risk/benefit of the hypertensive therapy.

The phenomenon of rhythmic fluctuations in cardiovascular variables such as heart rate (HR) or arterial blood pressure (BP) has attracted the attention of workers in both pure and applied research. In recent years, the possibility of quantifying these oscillations by using power spectral analysis has aroused a growing interest. We investigated the fluctuations which underly the spontaneous variability of BP and HR in conscious rats. Intrafemoral pulsatile BP was computed to generate evenly spaced signals (systolic, diastolic, mean BP, HR) at 200 ms intervals. This equidistant sampling allowed a direct spectral analysis using a Fast Fourier Transform algorithm. Systolic Blood Pressure (SBP) and HR exhibited low frequency oscillations (Mayer waves, 20-605 mHz) and a high frequency oscillation related to respiration (1,855 mHz). The respiratory fluctuations in HR were almost abolished by vagal blockade (atropine). HR fluctuations in the low frequency regime were diminished by vagal blockade or cardiac sympathetic blockade (atenolol). The respiratory frequency fluctuations in SBP were markedly increased by alpha sympathetic blockade (prazosin). On the contrary the low frequency oscillations in SBP were reduced by alpha sympathetic blockade. These data indicate that in conscious rats: 1) the HR oscillation with respiration is vagally mediated, 2) the HR fluctuation in the low frequency regime is jointly mediated by beta sympathetic and parasympathetic activities, 3) the respiratory oscillation in SBP depends on fluctuations in cardiac output and is normally counteracted by the sympathetic tone, 4) the low frequency oscillations in SBP reflect the sympathetic activity to the resistance vessels.

The ability of endogenous myocardial catecholamines to participate in the development of myocardial cellular alterations during a short period of severe hypoxia (30 min) was studied in isolated, Langendorff-perfused rat heart preparation, arrested by a high potassium concentration (16 mM) and perfused in the absence of exogenous substrate (Table I). Tyramine, which accelerated catecholamine depletion, also increased myocardial cell damage as assessed by a higher lactate dehydrogenase (LDH) release and a more marked reduction in cellular levels of high energy phosphates and glycogen (Table II). On the other hand, under conditions of beta-blockade (atenolol), hypoxia-induced tissular damage was reduced (Table II). These changes could be related to modifications in the cellular content of cyclic AMP (cAMP) since cAMP was consistently higher during the first 30 min of hypoxic perfusion than in control normoxic hearts (Table III) whereas cyclic GMP content remained unchanged. Moreover, interventions increasing cellular content of cAMP (theophylline, dibutyryl-cAMP) also increased hypoxic damage (Table IV), whereas N-methyl imidazole which reduced cellular content of cAMP lessened hypoxia-induced cellular alterations (Table IV). It is concluded that cellular lesions developing during the first 30 min of hypoxia in isolated arrested rat heart preparation perfused without exogenous substrate could be related to intracellular accumulation of cAMP occurring under the effect of endogenous catecholamine release.

1. The preventive effects against genetic hypertension development (GHD) of seven antihypertensive drugs chronically administered to the young SHRs from their 5th to their 13th week of age have been investigated. 2. While prazosin (20 mg/kg) and hydrochlorothiazide (6,5 and 25 mg/kg) are ineffective and while YC 93, a calcium-antagonist (10, 30, 100 mg/kg) exerts only a slight protective effect, captopril (30 and 100 mg/kg), dihydralazine (25 mg/kg) and atenolol (200 mg/kg) strongly prevent GHD. 3. Captopril and dihydralazine oppose GHD by inhibiting the progressive increase in peripheral resistance (PR) which normally occurs with ageing in SHRs. Simultaneously, these two drugs do not affect the cardiac output (CO) but increase plasma renin concentration (PRC). On the other hand, atenolol opposes GHD mainly by reducing CO and PRC while it simultaneously reinforces the progressive increase of PR with age. Captopril and atenolol, unlike dihydralazine, limit SHRs' myocardial hypertrophy. 4. After 14 weeks of treatment, arterial blood pressure (BP) of dihydralazine - and atenolol-treated animals meets control animals BP within 4 weeks whereas captopril preventive effects are still present up to 12 weeks after treatment discontinuation. Wit atenolol and captopril ther is after treatment discontinuation a good correlation between the evolution of heart weight/body weight and BP, which suggests that captopril could temporarily oppose the myocardial structural alterations which usually accompany GHD.

Myocardial hypoxia, induced by arrest of the artificial ventilation of anaesthetized open-chest rats, was utilized in order to study some aspects of the regulation of myocardial glycogen metabolism. Atenolol, a cardioselective beta-adrenergic receptor antagonist, and verapamil, an inhibitor of sarcolemmal calcium transfer, were used to determine the respective role of adenosine 3', 5'-cyclic monophosphate (cAMP) and calcium in the activation of the enzymes of glycogen phosphorolysis and synthesis. Glycogen degradation is reduced by atenolol treatment, as a consequence of a reduced activation of glycogen phosphorylase. Verapamil treatment has no significant effect, neither on the enzyme activation nor on the glycogen utilization. The activation of glycogen synthase, expressed by the conversion of the enzyme from the D to the I form, which results from the decrease in glycogen stores during hypoxia, is lowered under the effect of both drugs. However, in the beta-blocker treatment case, this effect results from a lower glycogen depletion while this effect is more specific in hearts from rats treated with verapamil. Under the effect of verapamil, the reduction of synthase activation, for a similar depletion of glycogen stores, was confirmed by experiments using isolated rat hearts submitted to ischaemia. These results show that: 1. the glycogenolysis in the hypoxic myocardium in situ is mainly controlled by a cAMP-dependent enzyme conversion or by metabolic allosteric effectors; 2. the activation of myocardial glycogen synthase, which is essentially correlated to the reduction of glycogen stores, is also calcium-dependent and most probably totally cAMP-independent.

Of 58 patients treated with captopril, 3 have now received the drug for more than 2 years and 22 for more than one year. This study concerns 38 patients treated for 6 months, captopril having been given alone during the first 2 months. They all had severe hypertension (diastolic BP Greater Than 110 mmHg) which had resisted previous treatments in normally effective doses, including at least one beta-blocker, dihydralazine and a diuretic. After 6 months blood pressure levels were normal in 53% of the patients, reduced in 31% and unchanged in 16%. Clinical improvement was habitual with, in particular, disappearance or decrease of tiredness and dyspnoea. Since some side-effects of the drug, such as granulopenia, proteinuria and ageusia, are mainly observed with high dosage, captopril is usually administered in doses lower or equal to 400 mg/day. In resistant or malignant hypertension it must be used in combination with salt-free diet, a beta-blocker and/or prazosin. Clinical, haematological and renal surveillance is necessary during treatment. When these precautions are observed, captopril constitutes a very useful drug for the treatment of patients with severe resistant hypertension.

This study involved 113 patients (mean age 50 +/- 14 years) with diastolic blood pressure above 95 mmHg. The patients abstained from taking any antihypertensive drug and received a placebo for one week before entering felodipine, a new calcium antagonist (5 mg x2/day for 2 weeks, then 10 mg x2/day) or atenolol (100 mg/day). There was no significant difference between the two treatment groups. Atenolol tended to be more effective in young subjects and felodipine in subjects aged 60 years or more. Heart rate was more reduced by atenolol than by felodipine (P less than 0.01). Undesirable side-effects were recorded by means of an open questionnaire. Their incidence was 23 per cent during the week under placebo and 84 per cent and 80 per cent respectively during treatment with felodipine or atenolol. The most frequent side-effects were oedema of the ankles and headache under felodipine, fatigue and headache under atenolol. Alkaline phosphatase levels were higher in the felodipine group (P less than 0.05), and a slight rise in blood potassium level (0.2 mmol/l) was noted in the atenolol group (P = 0.001), but these values remained within normal limits.

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).

The effectiveness and acceptability of perindopril (P) as an antihypertensive agent were compared with those of captopril (C), atenolol (A) and a combined hydrochlorothiazide + amiloride diuretic (D) in three simultaneous multicentre double-blind trials involving 165, 173 ans 165 patients respectively. After a 1 month placebo period, 3 groups of patients with essential hypertension whose DAP in supine position ranged from 95 to 125 mmHg (means: 103.9, 106.2 and 105.2 mmHg respectively) were allocated at random to treatment with either P (4 mg once a day) or C (25 mg b.d.) or A (50 mg once a day) or D (hydrochlorothiazide 50 mg + amiloride 5 mg once a day) during 3 months. The patients were re-examined monthly and their treatment was modified if their BP was insufficiently controlled (DAP greater than 90 mmHg): first, the dosage of the drug was doubled, then another antihypertensive agent was added, which was either a diuretic (studies with C or A) or a beta-blocker (studies with D). After 3 months, in the monotherapy group BP was controlled in 49 p. 100 of patients on P versus 49 p. 100 on C; 55 p. 100 on P versus 48 p. 100 on A and 72 p. 100 on P versus 72 p. 100 on D. The majority of patients who received P alone were controlled with 4 mg, and only 15 p. 100 required 8 mg. In cases where BP control necessitated a therapeutic combination, the addition of a diuretic was more effective with P than with C (26 p. 100 versus 8 p. 100) or A (23 p. 100 versus 10 p. 100), whereas the addition of a beta-blocker was less effective with P than with D (5 p. 100 versus 13 p. 100). The total percentage of controlled patients was greater with P than with C (75 p. 100 versus 57 p. 100, p = 0.016) or with A (78 p. 100 versus 58 p. 100, p = 0.006); there was non significant difference between P and D (78 p. 100 versus 84 p. 100). The percentages of patients who discontinued treatment were similar with P (6 p. 100 at most), C (4 p. 100), A (5 p. 100) and D (5 p. 100). Most of the side-effects reported with P were minor and unspecific, and their incidence was close to that observed with the other drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Bopindolol (Sandoz) in single daily doses of 1 and 2 mg was compared with atenolol (ICI) in single daily doses of 50 and 100 mg in respect of antihypertensive effect in a population of 33 patients divided by random allocation into 4 groups and treated for 12 months. Statistical analysis of the more than 4000 blood pressure readings obtained with a noninvasive ambulatory blood pressure recorder indicates equivalence of efficacy between bopindolol 1 mg, bopindolol 2 mg and atenolol 100 mg, with atenolol 50 mg less effective. Bopindolol's long duration of effect was reflected in lower morning values and in the absence of hypotension in the circadian profile.

Cardiac output (isotopic dilution method) and systolic time intervals were studied in 11 sustained and 8 borderline essential hypertensive patients, before and after intravenous administration of atenolol, a potent beta-blocking agent. Atenolol decreased significantly (p less than 0.01) cardiac output and heart rate. In borderline hypertensives, the preejection periods were significantly reduced. Atenolol prolonged the preejection periods more significantly (p less than 0.01) in borderline than in permanent hypertensives. Non invasive hemodynamic technics enabled the cardiac performance to be evaluated in hypertensives and the contribution of neurogenic factors in borderline hypertension to be estimated.