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Hypertensive patients treated with nonselective beta adrenergic blocking agents may show remarkable hemodynamic changes with administration of epinephrine clinically. We have attempted to investigate the effects of the interaction between beta blockers (a nonselective beta blocker, pindolol, and a cardioselective beta blocker, acebutolol) and a solution of 2% lidocaine containing 1:80,000 epinephrine on the hemodynamics of conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), as compared with the normotensive rats. The blood pressures (systolic and diastolic) and heart rate were measured indirectly by the photoplethysmographic tail cuff method. All drugs were administered intraperitoneally. We found that: (1) epinephrine with pindolol or acebutolol pretreatment did not cause significant hemodynamic changes in WKY; (2) in SHR, epinephrine in combination with pindolol induced remarkable hemodynamic changes (in particular, increase in diastolic blood pressure), which were prevented by phentolamine pretreatment, whereas epinephrine with acebutolol pretreatment induced no significant hemodynamic changes in these animals; (3) epinephrine in combination with pindolol caused pulmonary congestion or edema in SHR; this was confirmed by both quantitative analysis and histological investigations. These results suggest that pindolol blocked both beta 1 and beta 2 receptors, and therefore, this resulted in exaggerated alpha effects of epinephrine, a remarkable systemic vasoconstriction, and pulmonary congestion. In a clinical setting, great caution should be paid to the hypertensive patients, who are being treated with nonselective beta blockers, if epinephrine-containing local anesthetics are administered.

The cardioselective beta-adrenoblocker acebutolol used as a course therapy for 12 weeks was found to be a highly beneficial antihypertensive agent. The antihypertensive effect of the agent given in doses of 400-800 mg/day was as pronounced and prolonged as that of propranolol, 80-160 mg/day, though there is a tendency for acebutolol to show its complete or partial antihypertensive effect rather at the end of monotherapy than propranolol. At the same time the bradycardiac effect was more pronounced in propranolol therapy. The antihypertensive effect of acebutolol, 400-800 mg/day, was revealed after 2 weeks of its use and persisted within the entire 12 weeks of therapy. The drug was well tolerated. In contrast to propranolol, a non-selective beta-adrenoblocker having no intrinsic sympathomimetic activity, acebutolol failed to produce adverse effects, such as by decreasing cardiac output and increasing total peripheral vascular resistance. The agent had a less negative chronotropic effect.

A prospective study of the hemodynamic and renal changes was undertaken in 11 neonates whose mothers were treated with acebutolol for hypertension during pregnancy, compared with a control group of 11 infants born to normotensive mothers. Monitoring of the cardio-respiratory system was performed for a period of 4 days. Renal function was studied during 2 periods (12-36, 60-84 hours of life). Hemodynamic failure was observed in 5 of 11 children from treated mothers. The data concerning the renal function of treated group showed: 1) a diuresis significantly lower during the first period (p less than 0.05); 2) the absence of significant rise in the glomerular filtration rates during the second period; 3) a lower sodium balance during the 1st and 2nd periods (p less than 0.02 and p less than 0.05), a lower calcium balance during the 1st period (p less than 0.01). No relationship was found between the renal changes and the hemodynamic disturbances. The direct effect of the drug on the glomerular and tubular functions and/or the renal arteriolar vasomotricity could explain these changes in the renal function in the newborns prenatally exposed to acebutolol.

In six conscious dogs we compared the hemodynamic effects of propranolol, acebutolol, and acebutolol's primary metabolite at equipotent beta-blocking doses. Aortic pressure, heart rate, left ventricular end-diastolic pressure, dP/dt, and aortic flow velocity were measured 3 weeks after sterile surgery during three infusions of each drug. Only one drug was given on each day. The equipotent beta-blocking dose of each drug was obtained by comparing isoproterenol dose-response curves. All three drugs produced a fall in dP/dt. Left ventricular end-diastolic pressure increased in most dogs, but this was only significant for acebutolol. The heart rate tended to fall and the blood pressure rise, but this was variable and not significant. The concentration of the equipotent blocking dose of acebutolol was 44 times that of propranolol, and while the concentration of acebutolol's metabolite was 1.6 times that of acebutolol. In conclusion, at a concentration similar to acebutolol, acebutolol's metabolite has heart rate blocking and myocardial depressive effects similar to those of propranolol and acebutolol.

Thirteen beta-blocking agents with different pharmacological properties were administered orally to 161 outpatients with essential hypertension for 5 weeks to assess their hemodynamic effects. Cardioselective ones, such as atenolol, metoprolol and acebutolol, reduced mean blood pressure (MBP) and the cardiac index. (CI) without any changes of the total peripheral resistance index. (TPRI). In the total 44 patients treated with these drugs, a positive correlation (r = 0.529, p less than 0.005) was found between the decrease in MBP and that of TPRI, but the decrease in MBP did not correlate with that of CI. Effects of non-cardioselective ones were classified arbitrarily into the following 3 patterns: 1) reduction of CI of more than 0.50 L/min/m2 and a slight increase of TPRI by more than 150 dyne . sec . cm-5 . m2 (nadolol, propranolol, o.prenolol and penbutolol), 2) reduction of TPRI by more than 150 dyne . sec . cm-5 . m2 (pindolol, bunitrolol and labetalol) and 3) the intermediate hemodynamic responses between the two patterns described above (carteolol, bupranolol and bufetolol). In all these 3 groups, the decrease in MBP correlated with that of TPRI (the first group, n = 45, r = 0.557, p less than 0.005; the second, n = 37, r = 0.525, p less than 0.005; the third, n = 35, r = 0.612, p less than 0.005), but did not correlate with the decrease of CI. These results suggest that the antihypertensive effects of beta-blocking agents mainly depend on the reduction of peripheral resistance, although their pharmacological properties are not uniform and their cardiodepressant effects are variable. Reduction of cardiac performance with these beta-blocking agents seemed to be a consequence of overall pharmacological actions including beta-receptor blockade, central effects and membrane stabilizing effects, and it may be antagonized by intrinsic sympathomimetic activity and the reduction in afterload for the heart. Vascular beta-receptor blocking action may play a part in decreasing the degree of reduction of the total peripheral resistance index, while their intrinsic sympathomimetic action on the vascular site may induce vasodilating effects.

1. During a 28-day treatment period, 10 healthy volunteers in a cross-over, double-blind study received at random 200 mg of either acebutolol or labetalol twice a day. Each treatment period was followed by administration of a placebo over an equal length of time. 2. Only acebutolol reduced heart rate measured in the supine position significantly at rest, whereas acebutolol and labetalol reduced it significantly after exercise on the treadmill. 3. Only acebutolol lowered humeral pressure at rest but not after exercise. Neither drug produced a change in blood pressure in the ankle or in the first toe at rest or after exercise. 4. Blood flow measured by plethysmography was increased by labetalol in the calf by comparison with placebo and in the first toe by comparison with placebo and acebutolol. 5. Labetalol lowered peripheral resistance significantly in comparison with placebo in the calf and first toe. Acebutolol tended to lower the resistance insignificantly in the calf but to increase resistance in the first toe.

1 The acute cardiovascular effects of acebutolol were measured at constant paced heart rate in thirteen patients investigated for possible coronary artery disease, six of whom showed significant coronary stenosis with regional myocardial dysfunction, seven of whom proved normal. Acebutolol 0.75 mg/kg i.v. was given to three patients with coronary artery disease and three normals, and 1 mg/kg i.v. to the other patients.2 Measurements were made of cardiac output, left ventricular and arterial pressures, and left ventricular angiography. Isovolumic and ejection phase parameters of left ventricular function, and systemic vascular resistance were derived. Plasma levels of acebutolol were measured. 3 The acute effects of acebutolol were a slight fall in cardiac output, LV dp/dt and dP/dt/P. There was no change in LV or arterial pressures, no consistent change in LVEDP or EDV, and no consistent change in ejection fraction or mean VCF. These changes imply a small negative inotropic effect, more marked at the higher dose. 4 The effects of acebutolol differed in patients with ischaemic heart disease compared with normals in that LVEDP and EDV increased, mean VCF decreased and cardiac output was lowered more. 5 These data are consistent with myocardial and vascular effects of beta-adrenoceptor blockade more marked at the higher dose and more marked in patients with ischaemic heart disease.

Acebutolol ('Sectral'), a cardioselective beta-blocking drug, was administered intravenously in a dose of 25 mg to 10 patients with congestive cardiomyopathy. All of them were in a stable condition on antifailure regimens. The drug resulted in a statistically significant decline in left ventricular contractility as judged by peak left ventricular dP/dT and the contractility index. The mean aortic blood pressure also fell. There was a significant increase in end-diastolic and end-systolic left ventricular volumes. Mean values for heart rate, ejection fraction, left ventricular stroke work index, and cardiac output also fell, but the results were not statistically significant. Left ventricular distensibility as judged by the slope of the diastolic pressure-volume relation also improved significantly. A reduction in myocardial energy requirements, improved compliance, and lowering of arterial pressure would be haemodynamically advantageous. However, further cardiac dilatation and reduction contractility--the basic defects in congestive cardiomyopathy--could lead to further deterioration.

Systemic and coronary hemodynamic effects of acebutolol (10 mg i.v.), a cardioselective beta-adrenoceptor blocking agent were investigated in 11 patients with coronary artery disease and significant arterial obstructive lesions. Efficacy was assessed by simultaneous left and right heart catheterization and with an inlaying Webster thermodilution catheter in the coronary sinus. The data were compared with data from 7 other patients who received 2 mg i.v. of propranolol, a non-cardioselective beta-blocker. With acebutolol, (1) the heart rate was reduced significantly (p less than 0.001), (2) no significant changes were observed in the LVSP, LVEDP, mean PWP, LVmax dp/dt/p, LV negative dp/dt/p, CI, SWI and SPI, (3) CSF and MVO2 decreased significantly (p less than 0.01) 5 min after injection and (4) the CVR showed a significant elevation (p less than 0.05) after 5 min. With propranolol, (1) the heart rate decreased significantly (p less than 0.05), (2) there were no significant changes in LVSP and LVEDP, (3) the mean PWP increased significantly (p less than 0.05), (4) the LVmax dp/dt/p, CI and SWI decreased significantly (p less than 0.05), (5) the CSF and MVO2 decreased markedly (p less than 0.01) and (6) the CVR increased markedly (p less than 0.01). As compared to the effects of 2 mg i.v. of propranolol, those produced by acebutolol (10 mg i.v.) were characterized by a predominant negative chronotropic action with minimal negative inotropic action, combined with a reduction in CSF and MVO2. The findings suggest that the efficacy of acebutolol in pump failure caused by myocardial ischemia during effort angina is mediated by improvement of the myocardial oxygen demand-supply imbalance.

1 The effects of 5 mg/kg acebutolol given intravenously were investigated in anaesthetized dogs after (a) ligation of the left anterior descending coronary artery and (b) coronary reperfusion following 60 min of ligation of the anterior descending coronary artery. 2 Coronary artery ligation produced, after 4 to 6 h, persistent multiple ventricular ectopic beats and abnormalities of R and T waves and of the S-T segment. Administration of acebutolol, after the development of persistent ventricular arrhythmias, restored normal sinus rhythm within 5 min of injection. Electrocardiographic abnormalities were also reduced. 3 Coronary artery reperfusion (following 60 min of ligation) resulted in multiple ventricular ectopic beats, ventricular tachycardia and/or ventricular fibrillation. Pretreatment with acebutolol, 15 min before starting reperfusion, markedly reduced the arrhythmias. 4 Acebutolol did not affect peak inspiratory airway pressure. 5 Acebutolol produced significant bradycardia and slight, transient, hypotension. It was without effect on left ventricular systolic pressure, left ventricular end-diastolic pressure, cardiac output or pulmonary arterial pressure. 6 These results suggest beneficial effects of acebutolol in myocardial ischaemia and coronary reperfusion, without any significant risk of cardiodepression or bronchospasm.

Chronic administration of acebutolol (15 mg kg-1 s.c. three times a week for five weeks, then 30 mg kg-1 for three weeks) did not lower blood pressure in 17 and 33 weeks-old spontaneously hypertensive rats (SHR). At the end of this treatment, the plasma concentrations of acebutolol and diacetolol were measured by HPLC. After 24 h, acebutolol was absent from plasma while diacetolol was lower after chronic treatment than after acute administration. Twenty-four hours after the last injection of acebutolol, both isoprenaline-induced tachycardia and vasodilatation were reduced. The vasomotor agents, noradrenaline, bradykinin and angiotensin, exhibited the same activity in control and treated SHR. These findings suggest that the lack of antihypertensive effect of acebutolol in SHR may be the result of a decrease in diacetolol formation together with blockade of beta 2 vascular receptors.

A double-blind, placebo-controlled study of the haemodynamic and ventilatory effects of two beta 1-selective adrenoceptor blockers and their interaction with the beta 2-adrenoceptor agonist terbutaline was carried out in eight asthmatic patients. One hour after intake of placebo, metoprolol 100 mg or acebutolol 400 mg, increasing doses of terbutaline were infused. Before and one hour after ingestion of the medication and after each infusion of terbutaline, ventilatory and haemodynamic indices were measured. The two beta-blocking agents caused equal changes in basal ventilatory and haemodynamic indices. Terbutaline infusion caused a dose dependent increase in forced expiratory volume in one second (FEV1) and peak expiratory flow rate (PEFR), both during placebo and beta-blockade. Metoprolol did not affect the terbutaline-induced bronchodilatation. During acebutolol medication, however, the increase in FEV1 and PEFR induced by terbutaline was partly inhibited. Terbutaline infusion during placebo caused a dose-dependent increase in heart rate (HR) and systolic blood pressure (BP), and a decrease in diastolic BP. During acebutolol medication, these haemodynamic effects of terbutaline were completely blocked, but during metoprolol medication terbutaline still caused small changes in the same direction as during placebo, presumably because the vasodilator action of terbutaline was not inhibited. A negative correlation was found between the plasma levels of acebutolol and its metabolite N-acetyl acebutolol at the end of the study and changes in FEV1 and PEFR induced by terbutaline during acebutolol therapy as compared with placebo. The ventilatory and haemodynamic findings suggest a lower degree of beta 1-selectivity after oral administration of acebutolol as compared to metoprolol.

Arterial blood pressure and pulse rate changes following tracheal intubation were studied in 80 patients undergoing oral surgical procedures who received an etomidate/suxamethonium anesthetic induction sequence. Three treatment groups and a control group were used. Intravenous labetalol (1 mg/kg), acebutolol (0.25 mg/kg), lidocaine (2 mg/kg), and saline (1 ml), injected prior to anesthesia, were compared with respect to their effect on the hemodynamic consequences of direct laryngoscopy followed by the passage of an endotracheal tube. A pre-induction dose of labetalol was found to be more effective than acebutolol and lidocaine in attenuating the pressor response to instrumentation and intubation. Labetalol should prove most useful for those patients at risk from the transient hypertension and tachycardia following instrumentation and intubation.

Acebutolol is a relatively new beta-adrenoceptor blocking antagonist, possessing both beta 1-adrenoceptor selectivity and partial agonist activity (PAA). Its acute (24 h, 400 mg, twice daily) and long-term effects (3 weeks) on systemic and renal hemodynamics, body fluid volumes, hormones, and beta-adrenoceptor density on lymphocytes were studied in a single-blind placebo-controlled trial, in 10 hypertensive patients. The initial response to acebutolol (1-2 h) was a fall in heart rate (HR) (-9.6 +/- 2.7%), cardiac output (-16.0 +/- 3%), and stroke volume (SV) (-10.7 +/- 0.2%), and an increase in systemic vascular resistance (SVR) (18.0 +/- 3.9%). Mean arterial pressure (MAP) began to fall 2-3 h after dosing in parallel with a decrease in SVR. At the end of the acute study, MAP and SVR were decreased by 18.1 +/- 2.7% and 15.6 +/- 5.6%, respectively. By that time, HR and SV had returned to control values despite blockade of beta-adrenoceptors. After 3 weeks of treatment (mean dose of acebutolol 480 mg twice daily), the fall in MAP was 10.1 +/- 2.7% and HR was decreased by 13.0 +/- 2.3%. Renal blood flow and glomerular filtration rate did not change. Acute and long-term treatment had no effect on the density of lymphocyte-membrane beta-adrenoceptors. This could be explained by acebutolol's beta 1 selectivity or, alternatively, this could be due to the drug's PAA.

The aim of antiarrhythmic drug therapy is to terminate or suppress specific arrhythmias and improve cardiovascular function. Short-term studies of the new Class I drugs encainide, mexilitine, and tocainide have demonstrated only minor falls in cardiac index with modest rises in mean aortic pressure. In contrast, disopyramide has been shown to depress myocardial function in both animals and patient studies. Heart failure may be precipitated by therapy with disopyramide and electromechanical dissociation has been reported. Class II agents with beta-adrenergic blocking actions all produce a degree of myocardial depression. Atenolol resembles propranolol in patients with coronary artery disease in its hemodyanmic effects, whereas acebutolol is less of a depressant, resembling practolol. The Class III agent amiodarone has only a mild depressant effect associated with a reduction in afterload and an increase in coronary blood flow. The Class IV agent verapamil, which is a calcium channel blocker, has potent myocardial depressant actions and causes peripheral vasodilatation. Hypotension, heart failure, and shock have been precipitated particularly in patients receiving beta-blocking drugs concurrently. While all the new antiarrhythmic drugs currently studied will cause some degree of hemodyanmic depression in an appropriately high concentration, present investigations suggest that particular caution needs to be taken when disopyramide, aprindine, atenolol, and verampamil are administered either acutely by the intravenous route or chronically by the oral route.

The present study was undertaken in order to obtain further informations on non-beta-antiadrenergic properties of the four beta-sympatholytic agents acebutolol, oxprenolol, pindolol, and propranolol. Standardized experiments were performed using a chronically reserpinized canine preparation for the assessment of dose-response curves of changes in hemodynamics, left ventricular contractility, heart rate, AV-conduction time, and myocardial oxygen consumption especially at therapeutic doses. Our results show that acebutolol and oxprenolol, at doses clinically recommended, exert moderate positive inotropic effects but do not influence heart rate significantly. Pindolol has a strong both positive chronotropic and inotropic efficacy, even at small therapeutic doses. Propranolol produces neither chronotropic nor inotropic effects. In contrast to the literature acebutolol exerts direct cardiodepression at doses clinically used, whereas oxprenolol, pindolol, at propranolol have no direct cardiodepressant properties at those doses. Thus the relationship between the dose requirements for chronotropic and inotropic sympathomimetic effects differs for each beta-sympatholytic agents, and in may prove impossible to get an order of intrinsic sympathomimetic potency of beta-blockers comparing dose-response curves of heart rate changes only. As shown in the case of acebutolol, direct cardiodepression of beta-sympatholytic agents may occur at therapeutic doses.

1. ACTH (20 microgram/kg per day) produced an elevation in blood pressure associated with an increase in cardiac output in conscious sheep, due in the first 72 h to a rise in heart rate. Stroke volume did not rise until the fourth day of ACTH treatment. 2. Calculated total peripheral resistance did not change. 3. Intreavenous administration of acebutolol prior to and during ACTH administration did not modify the rise in blood pressure, but this was associated with a rise in total peripheral resistance. 4. These studies show that while ACTH-induced hypertension is usually associated with increased cardiac output, rather than total peripheral resistance it still occurs, but is associated with a rise in total peripheral resistance if the rise in cardiac output is prevented by beta-adrenoreceptor blockade.

Acebutolol 400 mg vs. propranolol retard 160 mg were investigated in a multicentral, double-blind, cross-over study for their action on blood pressure and heart rate in outpatients during ergometer exercise. A 2-week single-blind placebo control phase, which served as a wash-out and to eliminate placebo responders, preceded the 6-week treatment phase with propranolol (or acebutolol) followed by a further 6-week phase with acebutolol (or propranolol). At the end of each treatment phase a bicycle ergometer test was carried out, the values for 18 patients (from 26 completed investigations) were carried forward to the evaluation of the ergometry. The treatment groups were shown to be comparable. Acebutolol and propranolol produced a similar fall in systolic and diastolic blood pressure and heart rate at rest. During ergometer exercise, acebutolol led to a significantly lower increase in both systolic and diastolic blood pressure and heart rate than propranolol. The possible role of the intrinsic sympathomimetic activity (ISA) and the relative cardioselectivity of the test agents and the clinical impact of the hemodynamic findings with respect to morbidity and mortality are briefly discussed. Questioning at the end of the study revealed that significantly more patients preferred the treatment with acebutolol.

In patients with acute myocardial infarction the haemodynamic relevance of the ancillary pharmacological properties of cardioselectivity and of intrinsic sympathomimetic activity (ISA) possessed by beta-blocking drugs is unclear. The dose-response effects of atenolol and acebutolol, two cardioselective compounds, the latter also possessing a degree of ISA, were therefore compared in a single-blind, dose-response, crossover study in patients within 18 h of suffering an uncomplicated acute myocardial infarction. The logarithmic cumulative dosage schedule achieved plasma concentrations in the clinical therapeutic ranges for both atenolol (0.05 +/- 0.04-0.19 +/- 0.03 micrograms/ml) and acebutolol (0.22 +/- 0.14-0.8 +/- 0.29 micrograms/ml). Incremental doses of intravenous atenolol (cumulative, 1-8 mg) resulted in significant decreases in systolic blood pressure, heart rate, cardiac output, stroke volume, and stroke work index (p less than 0.01 for each). Pulmonary artery occluded pressure (p less than 0.05) and systemic vascular resistance (p less than 0.01) increased. Incremental doses of intravenous acebutolol (cumulative, 10-80 mg) also resulted in significant decreases in systolic blood pressure, heart rate, cardiac output, stroke volume, and stroke work index (p less than 0.01 for each). Systemic vascular resistance increased (p less than 0.01); there was no consistent change in the pulmonary artery occluded pressure. Within the limits of the experimental protocol, the additional property of ISA possessed by acebutolol resulted in no statistically significant haemodynamic differences from atenolol. This may reflect either an insufficient degree of ISA possessed by acebutolol to confirm the original hypothesis, or its haemodynamic irrelevance in the presence of the increased sympathetic tone that is frequently present following acute myocardial infarction.

Acute i.v. administration of 15 mg/kg acebutolol in normotensive (WKY), Okamoto (SHR) and Okamoto stroke-prone (SHR-SP) awake rats resulted in weak effects on blood pressure and in bradycardia more marked in SHR-SP. Thirty minutes after i.v. administration, lung and renal uptake of [14C]acebutolol was reduced in SHR compared to other rats. Muscle uptake was higher in SHR and blood concentration was higher in SHR-SP. Brain levels were low and similar in all rats. Plasma protein binding was identical in all rats. These results are discussed according to the characteristics of the three strains studied.

The acute hemodynamic effects of intravenous acebutolol, 50 mg, and propranolol, 10 mg, were evaluated in 12 patients undergoing diagnostic cardiac catheterization. Each patient received acebutolol or propranolol according to a list of randomization. Both acebutolol and propranolol depressed left ventricular function. There was a significant increase in left ventricular end-diastolic pressure at rest and after isometric exercise, with a concomitant decrease in cardiac index. Systemic vascular resistance was increased by both drugs. The increment after patients received acebutolol was not statistically significant; however, with propranolol it was statistically significant. The overall hemodynamic effects of acebutolol and propranolol are similar, but a quantitative difference exists in their effect on systemic vascular resistance. Acebutolol, a cardioselective agent, produces less of a peripheral vascular beta 2-blockade than does propranolol.

1 The cardiovascular effects of the beta-adrenoceptor blocking drugs, propranolol and acebutolol, on regional coronary blood flow and left ventricular function have been investigated in the conscious dog with developing myocardial infarction. 2 Propranolol (1 to 1.5 mg/kg) or acebutolol (4 to 5 mg/kg) were administered intravenously 2 to 3 h after occlusion of the left anterior descending coronary artery. 3 Propranolol or acebutolol administration resulted in a relative increase in flow to the ischaemic area of the myocardium, particularly to the subendocardium. 4 Propranolol produced a greater reduction in heart rate and myocardial contractility than acebutolol. 5 These results demonstrate that beta-adrenoceptor blocking drugs reduce myocardial oxygen consumption and increase coronary flow to the ischaemic area of the myocardium after coronary artery occlusion in the conscious dog.

The aim of this study was to assess the effects of the association of sublingual nifedipine and intravenous acebutolol on left ventricular inotropism. A series of 30 randomised patients underwent hemodynamic investigation repeated after a 30 minute interval comprising measurement of left ventricular (LVP) and aortic (AoP) pressures and ventriculography (Vo). Between the two Vo, Group I (N = 10) were given 20 mg sublingual nifedipine (N), Group II (N = 0) were given I mg/Kg acebutolol (A) intravenously in 5 minutes, and Group III (N = 10) the association of 20 mg sublingual N and I mg/Kg intravenous A. All patients had normal resting left ventricular function (ejection fraction greater than 0,55). In Group I, a significant improvement in left ventricular function with reduction of end diastolic pressure, increase ejection fraction, VCF and cardiac index was observed. THese changes were secondary to the reduction in aortic impedence with no effects on the contractile element (assessed by end systolic pressure/end systolic volume - ESP/ESV - ratio). In Group II, a significant reduction in these indices of left ventricular function was recorded secondary to a reduction in contractility. Group III had a special hemodynamic profile comprising: a reduction in afterload identical to that observed in Group I; a significantly greater reduction in the ESP/ESV ratio than in Group II; a greater reduction in the indices of left ventricular function (especially EF, VCF and CI) than in Group II, but the difference was not significant. The data obtained under the conditions of this acute hemodynamic investigation in patients with normal basal left ventricular function may be summarised thus: 1) Nifedipine alone has no detectable negative inotropic effects. 2) The association with acebutolol, nifedipine seems to potentiate myocardial depression (ESP/ESV). 3) This therapeutic association, the value of which has already been demonstrated in coronary insufficiency should be used carefully without precise knowledge of the left ventricular function.

The acute effects of propranolol and acebutolol on blood pressure, heart rate and hormonal changes during graded treadmill exercise were studied in patients with essential hypertension. Both of propranolol (2 mg i.v.) and acebutolol (10 mg i.v.) lowered the pre-exercise hemodynamic parameters and suppressed the elevation of systolic blood pressure, heart rate and pressure-rate product during exercise, but did not show any significant effect on diastolic blood pressure. Although these drugs increased plasma norepinephrine concentration (PNE) at rest and during moderate exercise, they failed to affect PNE at submaximal exercise. Plasma renin activity at rest and during exercise were more strongly suppressed by propranolol than acebutolol. Plasma aldosterone concentration was not affected by these drugs. Propranolol and acebutolol showed similar acute effects on blood pressure, heart rate and hormonal profiles at rest and during exercise within the doses used in this study. These results indicate that beta 1 adrenoceptor selectivity and intrinsic sympathomimetic activity may not play an important role in the acute antihypertensive effect at rest and during exercise and that both beta blockers have beneficial antihypertensive effects during exercise on patients with essential hypertension.