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PubMed1983

Detrimental effect of propranolol in patients with coronary arterial spasm countered by combination with diltiazem.

This study determines, with quantitative variables, if propranolol is detrimental in patients with documented coronary arterial spasm and if this drug can be used in combination with calcium antagonists. Eleven patients with documented coronary spasm were entered prospectively in a study with 4 phases of 2 days each: (1) control, (2) diltiazem or propranolol (mean 225 +/- 75 mg/day), (3) propranolol or diltiazem (360 mg/day), (4) propranolol and diltiazem. The effects of the drugs were assessed by the detection of ischemic electrocardiographic episodes (24-hour electrocardiographic monitoring) and provocative tests with ergonovine. During the period of treatment with propranolol, the number and the duration of attacks increased and provocative tests had positive results in all patients. Diltiazem completely abolished spontaneous episodes, but 6 of 11 patients remained sensitive to the administration of ergonovine. The association of the 2 drugs led to a disappearance of ischemic episodes. In conclusion, propranolol is ineffective in patients with coronary artery spasm. It can be used in combination with diltiazem, but without any advantage over diltiazem alone.

Adult↗
PubMed1984

Combined verapamil and propranolol for supraventricular tachycardia.

The electrophysiologic effects of intravenous verapamil and propranolol were compared alone and in combination in 14 patients (aged 21 to 69 years) with paroxysmal supraventricular tachycardia (SVT). Ten patients had atrioventricular (AV) reentry utilizing a manifest (7 patients) or concealed (3 patients) accessory pathway. Four patients had AV nodal reentry. Electrophysiology studies were performed using standard techniques in the control state and after verapamil (0.15 mg/kg intravenous bolus and 0.005 mg/kg/min). The next day, studies were repeated after propranolol (0.1 mg/kg) and a combination of verapamil and propranolol. No adverse effects occurred with the drug combination. Each drug intervention prolonged anterograde functional refractory period of the AV node (control, 370 +/- 50 ms; verapamil, 446 +/- 90 ms; propranolol, 436 +/- 92, p less than 0.05), with the greatest increase occurring after the drug combination (502 +/- 103 ms, p less than 0.001). In 2 patients prolonged sinus node recovery time developed after the drug combination. Verapamil or propranolol prevented SVT induction in 7 patients (50%). However, only the drug combination prevented reinduction of sustained SVT in 6 patients. These 6 patients were treated chronically with verapamil and propranolol, with no recurrence of SVT in any patient after 2 to 26 months.

Adult↗
PubMed1985

Single and combined therapy for systemic hypertension with propranolol, hydralazine and hydrochlorothiazide: hemodynamic and neuroendocrine mechanisms of action.

The antihypertensive mechanisms of single and combined therapy with a beta-adrenergic antagonist (propranolol) and a vasodilator (hydralazine) were investigated in 9 patients with moderately severe hypertension, who were receiving maintenance diuretic (hydrochlorothiazide) treatment. Hemodynamic and neuroendocrine responses were determined at rest and during lower body negative pressure, and dynamic and static exercise stress after the chronic administration of propranolol and hydralazine, given alone or in combination. All 3 drug regimens, each administered for at least 10 weeks, reduced blood pressure (p less than 0.05) compared with diuretic-only therapy in patients at rest, in both the supine and standing position, and during lower body negative pressure and dynamic exercise. There was a significant additive antihypertensive effect when propranolol and hydralazine were combined. Only combination therapy effectively lowered pressure during static exercise. The regimens produced divergent effects on the supine cardiac output: a decrease with propranolol (p less than 0.05), no change with combination therapy and an increase with hydralazine (p less than 0.05). Both hydralazine and combination therapy significantly reduced supine total peripheral resistance (p less than 0.05), whereas propranolol produced no change. All 3 drug treatments significantly reduced total peripheral resistance during upright rest and dynamic exercise (p less than 0.05), without changing cardiac output or maximal exercise capacity. During exercise, cardiac output was maintained in patients treated with propranolol and in those treated with combined therapy by increases in stroke volume (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Propranolol in acute myocardial infarction: the MILIS experience.

The results of the propranolol limb of the Multicenter Investigation of the Limitation of Infarct Size are reviewed. A total of 269 patients, who presented with symptoms and electrocardiographic signs suggesting acute myocardial infarction were randomized to acute intravenous and subsequent oral therapy with propranolol (n = 134) or placebo (n = 135). Eligibility for acute beta-blocker therapy was determined on the basis of readily available, noninvasive tests. Therapy was started at an average time of 8.5 hours after onset of symptoms. The full induction dose of intravenous propranolol (0.1 mg/kg) was tolerated by 90% of treated patients, and oral maintenance therapy was being continued in 82% of treated patients on the second hospital day. There was a significant reduction in heart rate throughout maintenance therapy with propranolol, which continued through the tenth hospital day. There was no significant difference in the incidence of congestive heart failure between propranolol- and placebo-treated groups. There was also no significant difference between the 2 groups in infarct size estimated by measurement of serum CK-MB, planimetry of infarct area on technetium pyrophosphate myocardial scintigrams or R-wave measurements in patients with transmural anterior and inferior infarcts. There was no significant difference in mortality between the 2 groups during an average of 36 months' follow-up. Although propranolol can be administered safely to patients with acute myocardial infarction who are selected on the basis of simple clinical criteria, there is no evidence of reduction of infarct size when beta blockade is begun 8.5 hours after the onset of symptoms.

Adrenergic beta-Antagonists↗
PubMed1987

Diltiazem versus propranolol in essential hypertension: responses of rest and exercise blood pressure and effects on exercise capacity.

Both beta-blocking and calcium channel-blocking drugs are being used with increasing frequency as initial therapy for essential hypertension. The present study was designed to compare the antihypertensive effects of a beta-blocking drug, propranolol, with a calcium channel-blocking drug, diltiazem, at rest and during upright bicycle exercise and to determine whether exercise capacity is altered by these therapies. Twenty-one patients with uncomplicated systemic hypertension and a diastolic blood pressure (BP) of 95 to 110 mm Hg without medication were randomly assigned to propranolol or diltiazem therapy in a double-blind manner. The total daily dosages were titrated as needed, from 160 to 480 mg of propranolol (mean 371 mg) and 120 to 360 mg of diltiazem (mean 307 mg) over 12 weeks, and the titrated dose was maintained for 4 additional weeks. Both drugs significantly reduced supine BP (from 149 +/- 14/101 +/- 4 to 136 +/- 17/89 +/- 10 mm Hg with propranolol and from 157 +/- 14/103 +/- 4 to 144 +/- 13/93 +/- 8 with diltiazem. Only diltiazem reduced BP during submaximal exercise, but both agents produced significant responses during maximal exercise. Diltiazem had no effect on maximal heart rate, exercise duration or O2 uptake, whereas propranolol reduced maximal VO2 from 27 +/- 6 to 22 +/- 6 ml/min/kg (p less than 0.01) and also shortened duration of exercise. Propranolol, despite its effects on heart rate, maintained the workload VO2 relation at submaximal loads, suggesting an increased oxygen delivery. However, these adaptive mechanisms appear to be insufficient during maximal effort.

Blood Pressure↗
PubMed1987

Acute hemodynamic effects of intravenous nicardipine in patients treated chronically with propranolol for coronary artery disease.

Intravenous nicardipine, 5 mg, was infused over 5 minutes in 2 comparable groups of 8 patients with chronic coronary artery disease but no clinical signs of heart failure. Eight patients had received no previous treatment and served as a control group; 8 other patients had received long-term treatment with large doses of propranolol. The hemodynamic responses to nifedipine were similar in the 2 groups, but was greater in patients taking propranolol. At 10 minutes, systemic vascular resistance decreased by 47% in patients taking propranolol and by 39% in the control group; mean aortic pressures decreased by 25% and 10%; heart rate increased by 23% and 19%; and cardiac index increased by 45% in both groups. At 20 minutes, left ventricular end-systolic volume index decreased by 20% in patients taking propranolol and 15% in the control patients; angiographic stroke index increased by 19% and 8%; left ventricular ejection fraction increased by 22% and 11%; and mean circumferential fiber velocity increased by 46% and 32%. Intravenous nicardipine infusion (5 mg) did not induce negative inotropic effects in patients with chronic coronary heart disease, and no evidence of congestive heart failure was seen, even in patients receiving large doses of propranolol. Nicardipine counteracted the potential deleterious effects of propranolol; increased peripheral vascular resistance and left ventricular stroke work and decreased cardiac output.

Adult↗
PubMed1988

Electrophysiologic effects of propranolol in intraventricular conduction disturbance.

Sixteen patients underwent electrophysiologic studies before and after intravenous infusion of propranolol, 0.1 mg/kg. All of them had intraventricular conduction disturbances. A significant (p less than 0.01) increase occurred after propranolol in the mean spontaneous cycle length (mean change 122 ms) and the AH interval (mean 28 ms). The HV interval did not change significantly. The effective refractory period of the His-Purkinje system increased in 4 of 5 patients (mean net change 44 ms, p greater than 0.10). In 7 patients with phase 3 infranodal block, the longest cycle length for producing block increased after propranolol in 5 and remained unchanged in 2 (mean increase 40 ms, p less than 0.02). Two patients showed phase 4 atrioventricular block. Propranolol increased the critical cycle length by an average of 120 ms. Propranolol-induced bradycardia restored stable atrioventricular conduction in 2 patients with intermittent 2:1 block but facilitated the occurrence of high grade infranodal block in 1 patient. Thus, propranolol can impair His-Purkinje conduction in patients with preexisting infranodal abnormalities.

Aged↗
PubMed1988

Effect of propranolol on the left ventricular response to the Valsalva maneuver in normal subjects.

Ten normal subjects performed the Valsalva maneuver before and after the administration of propranolol (1 mg/kg). Changes in left ventricular (LV) size and function were assessed with noninvasive techniques (echocardiography and sphygmomanometer). Data were obtained at baseline, at 20 seconds of the strain phase (phase II) and 10 seconds after the release of strain (phase IV). In the control state (before propranolol), blood pressure decreased during phase II and exceeded baseline after the release of strain ("overshoot") in phase IV; after the administration of propranolol, the pressure overshoot characteristic of phase IV was no longer present. End-diastolic dimension decreased during the strain phase, but returned to baseline values during recovery in both control and propranolol states. LV stress-dimension and stress-shortening relations before and after propranolol indicate that an increase in LV contractility beginning during phase II and extending into phase IV was attenuated after propranolol. Although the absence of phase IV blood pressure overshoot may be clinically useful in identifying patients with impaired left ventricular function, beta-adrenergic receptor blocking agents can also produce this hemodynamic response in the presence of normal ventricular function.

Adult↗
PubMed1989

Effect of intravenous propranolol or verapamil on infant orthodromic reciprocating tachycardia.

The effects of intravenous verapamil (0.15 mg/kg) and propranolol (0.2 mg/kg) with regard to atrioventricular (AV) conduction and tachycardia termination during paroxysmal atrial tachycardia were compared in 2 groups of infants (verapamil n = 14, propranolol n = 18, mean age 80 +/- 21 days, range 1 to 364). Using transesophageal recording techniques, tachycardia cycle length, AV intervals and ventriculoatrial intervals were measured before and after drug administration. Both intravenous propranolol and verapamil significantly prolonged tachycardia cycle length and AV interval (cycle length--propranolol 230 +/- 30 to 262 +/- 33 ms, p less than 0.05, verapamil 223 +/- 38 to 245 +/- 32 ms, p less than 0.05; AV interval--propranolol 98 +/- 26 to 126 +/- 38 ms, p less than 0.05, verapamil 96 +/- 19 to 109 +/- 24 ms, p less than 0.05). Neither drug prolonged the ventriculoatrial interval. Tachycardia terminated after intravenous verapamil in 11 of 14 infants (79% efficacy rate). Tachycardia terminated in 0 of 18 after intravenous propranolol (0% efficacy rate). In 8 infants an atrial deflection was recorded on the esophageal electrocardiogram at the time of tachycardia termination after intravenous verapamil, which suggested that tachycardia terminated by block occurring in the AV node. In 2 infants a ventricular deflection was recorded at the time of tachycardia termination after verapamil, which suggested that block occurred in the accessory connection. Both drugs prolonged tachycardia cycle length by prolonging AV conduction to a similar degree.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiography↗
PubMed1990

Effects of cigarette smoking and propranolol in survivors of acute myocardial infarction.

The effect of propranolol on mortality and reinfarction after acute myocardial infarction (AMI) in cigarette smokers and nonsmokers was studied in the Beta Blocker Heart Attack Trial. Cigarette smokers (n = 2,332) were 5 years younger than nonsmokers and had a lower incidence of diabetes mellitus, systemic hypertension, previous AMI and cardiomegaly. Among cigarette smokers, the placebo group had a higher total mortality rate than the propranolol group (11.0 vs 7.4%, p less than 0.0008) and more sudden cardiac deaths (7.1 vs 4.6%, p less than 0.009). In nonsmokers the placebo group had a mortality (7.9 vs 7.1%, p greater than 0.64) similar to the propranolol group. After baseline adjustment, cigarette smokers were estimated to have 1.6 times the risk of dying as compared to nonsmokers (p less than 0.0007). Adjusting for baseline differences, both treatment with propranolol and nonsmoking were predictors of survival. No detectable nonsmoking/propranolol interaction could be identified. In survivors of AMI a beneficial effect of propranolol is observed for cigarette smokers. Nevertheless, cigarette smoking continues to be a risk factor for mortality after AMI even for those receiving propranolol.

Double-Blind Method↗
PubMed1990

Propranolol-induced lipid changes and their prognostic significance after a myocardial infarction: the Beta-Blocker Heart Attack Trial experience.

Beta blockers represent the only documented effective long-term prophylactic treatment for patients after myocardial infarction (MI). Concern continues to be expressed about the lipid-altering effects of their long-term use, especially beta blockers without intrinsic sympathomimetic activity such as propranolol. Data collected for the Beta-Blocker Heart Attack Trial, the largest long-term clinical trial of beta-blocker use in patients after MI, have been analyzed to address the following questions. To what extent does propranolol alter lipid levels at least 6 months after MI and initiation of therapy? How predictive of subsequent coronary events and mortality are lipid levels 6 months after MI? Is there any evidence that altered lipid levels attenuate any of the beneficial effect of propranolol on coronary morbidity and mortality? By the 6-month post-MI visit, propranolol was shown to raise serum triglyceride levels by about 17% (approximately equal to 35 mg/dl) and lower serum high density lipoprotein (HDL) cholesterol by about 6% (approximately equal to 3 mg/dl). There was no effect on total cholesterol or low density lipoprotein cholesterol. In other analyses, no lipid measured 6 months after the MI was strongly predictive of subsequent coronary events or mortality. For example, every 1-mg-lower HDL value was associated with only a 0.7% relative increase in the mortality rate. Theoretically, the estimated relative increase on all-cause mortality associated with propranolol-induced HDL reduction is about 2%. In multivariate analyses adjusting for changes in HDL and serum triglyceride, propranolol-induced beneficial reductions in mortality and morbidity remained on the order of 20%, 10 times the estimated hazard.

Adult↗
PubMed1987

Multicenter comparison of the nifedipine gastrointestinal therapeutic system and long-acting propranolol in patients with mild to moderate systemic hypertension receiving diuretics. A preliminary experience.

The efficacy and safety of nifedipine in a gastrointestinal therapeutic system (GITS) push-pull osmotic pump formulation was compared with long-acting propranolol in 49 patients with mild to moderate hypertension already receiving diuretics. Using a two-week placebo run-in, double-blind study design, patients were randomly assigned to receive nifedipine GITS (n = 24) in doses of 30 mg, 60 mg, or 90 mg once daily; or long-acting propranolol (n = 25) in doses of 80, 160, or 240 mg once daily. Previous diuretic therapy was continued. Sitting and five-minute standing blood pressure and heart rate measurements were made 24 hours after dosing. At the endpoint of treatment, both nifedipine GITS and sustained-release propranolol reduced blood pressure compared with placebo (p less than 0.001) in the sitting and standing positions. Nifedipine GITS was more effective in lowering standing systolic blood pressure than was propranolol (p less than 0.02). Propranolol caused a greater reduction in resting heart rate than did nifedipine GITS (p less than 0.003). Both drugs were well tolerated. Nifedipine GITS is an effective and safe once-daily drug for use in patients with hypertension who are already receiving diuretics, may be more effective than sustained-release propranolol, and may be better tolerated than conventional nifedipine capsules.

Adult↗
PubMed1975

Treatment of thyrotoxicosis during pregnancy with propranolol.

The treatment of two pregnant thyrotoxic patients with propranolol alone is discussed. One patient had a spontaneous remission during pregnancy wile taking propranolol. In the other patient treatment with propranolol allowed postponement of definitive therapy until after delivery, when the fetus was no longer at risk. There were no complications of therapy in either patient and both infants were normal. The use of propranolol in thyrotoxicosis is discussed and the pertinent literature is reviewed. Regional anesthesia is preferred over general anesthsia in patients taking propranolol. Patients taking propranolol who require general anesthesia for delivery should have continuous monitoring of electrocardiogram and central venous pressure. To this date no method of therapy has been free of fetal side effects. Surgical treatment is associated with occasional abortion or premature labor; antithyroid medication occasionally results in fetal goiter or cretinism.

Adolescent↗
PubMed1985

Propranolol inhibits the maturational effect of adrenocorticotropin in the fetal sheep lung.

We reported previously that metyrapone inhibited the maturational effect of adrenocorticotropin in the fetal sheep lung, even in the presence of exogenous glucocorticoids. To examine the role of beta-adrenergic input in this response we examined lung maturation in fetal sheep treated for 100 hours in vivo with adrenocorticotropin (66 ng/min for 15 minutes every 2 hours, n = 5); adrenocorticotropin plus propranolol (40 micrograms/min, n = 4), or saline solution (n = 8). Pulmonary maturation was assessed by pressure-volume curves, phospholipid content, and morphologic features. The basal cortisol level rose from less than 5 to 32.0 +/- 12.1 and 83.5 +/- 8.0 ng/ml in the adrenocorticotropin and adrenocorticotropin plus propranolol groups, respectively. The adrenal:body weight ratio (X 10(-4)) rose from 1.43 +/- 0.12 in the saline solution group to 2.90 +/- 0.16 and 2.51 +/- 0.14 in the adrenocorticotropin and adrenocorticotropin plus propranolol groups, respectively. Lung distensibility (milliliters of air per gram of lung) rose from 1.10 +/- 0.14 to 1.90 +/- 0.20 in the adrenocorticotropin group but was unchanged (0.98 +/- 0.24) in the adrenocorticotropin plus propranolol group. Phosphatidylcholine (milligrams per gram of lung) in the lung lavage rose from 0.07 +/- 0.02 to 0.23 +/- 0.11 in the adrenocorticotropin group but was not significantly changed (0.12 +/- 0.06) in the adrenocorticotropin plus propranolol group. We conclude that propranolol inhibits the maturational effects of adrenocorticotropin on the fetal lung, which implies that the mechanism of pulmonary maturation is not solely dependent on endogenous cortisol and must be mediated, at least in part, through adrenergic responses.

Adrenal Glands↗
PubMed1984

Biochemical and physiological adaptation to chronic propranolol treatment in the rat.

The biochemical and physiological aspects of isoprenaline sensitivity in normotensive rats were examined during and after abrupt withdrawal of chronic propranolol treatment. Serum propranolol concentrations in rats chronically treated for one month (0.125% propranolol in drinking water: 75-100 mg/kg/day) ranged from 7 to 23 ng/ml. At the height of the blockade, rats showed a decreased responsiveness in vivo to isoprenaline-induced increase in heart rate and fall in blood pressure; the ED50 values for isoprenaline being increased some 20- and 4-fold respectively. There was a 180% increase in beta-receptor number in sarcolemmal membranes isolated from ventricular muscle of these animals, together with increased basal (290%), fluoride- (100%), forskolin- (80%) and isoprenaline-stimulated (125%) adenylate cyclase activity. Twenty-four hours after propranolol withdrawal, serum propranolol concentrations were reduced by over 95%. At this time rats exhibited increased chronotropic and blood pressure responses to i.v. isoprenaline, indicated by the reduced ED50 values (2-fold and 12-fold respectively compared to controls). In addition, cardiac sarcolemmal beta-receptor number and adenylate cyclase activities were still significantly elevated above those of controls; 35% increase in beta-receptor number and increases of 96, 26, 13 and 37% in basal, fluoride-, forskolin- and isoprenaline-stimulated adenylate cyclase activities respectively. Forty-eight hours after drug withdrawal serum propranolol concentrations were only just detectable at 0.5 +/- 0.1 ng/ml. Although sarcolemmal beta-receptor numbers were still elevated (23%) isoprenaline-stimulated adenylate cyclase activity had returned to control values. However, both the fluoride- and forskolin-stimulated enzyme activities were decreased below control values by 12 and 23% respectively, suggestive of a reduction in the catalytic capacity of the adenylate cyclase complex. In parallel with the reduction in beta-receptor number and adenylate cyclase activity, the chronotropic response to i.v. isoprenaline had also returned to control values. In contrast, the blood pressure response to i.v. isoprenaline was still elevated in these animals indicated by the 5-fold reduction in the ED50 value compared with control animals.

Adaptation, Physiological↗
PubMed1985

Reduced hepatic uptake of propranolol in rats with acute renal failure.

The effect of acute renal failure (ARF) on the hepatic uptake and metabolism of propranolol was investigated in relation to the hepatic clearance of the drug. ARF was induced by the subcutaneous injection of uranyl nitrate to rats. The uptake rate of propranolol in the isolated perfused liver was determined by the multiple-indicator dilution method and was found to decrease from 43.6 +/- 2.0 min-1 (mean +/- S.E.) in control to 29.4 +/- 1.7 min-1 in ARF (P less than 0.001). The recovery fraction of propranolol in effluent venous blood increased about twofold in ARF compared to control (P less than 0.05). The metabolic activity for propranolol was examined using the hepatic microsomal fraction prepared from control and ARF rats. There was no significant difference in the kinetics of oxidative metabolism of propranolol between two groups. These results suggest that the previously reported decrease in the hepatic clearance of propranolol in ARF is due to decreased hepatic uptake of the drug from the blood into the liver cells.

Acute Kidney Injury↗
PubMed1987

Inhibition of blood-brain barrier permeability to DL-propranolol by serum from acute renal failure rats.

The effect of uranyl nitrate-induced acute renal failure on the brain uptake of DL-propranolol was investigated in rats with a series of tissue-sampling single-carotid injection techniques. When the buffer solution was used as an injection solution, the brain uptake index (BUI), the extraction ratio (ET), and the blood-brain barrier (BBB) permeability-surface area product (PSapp) and PSu (corrected PSapp for the unbound fraction) in uremic rats were significantly lower than those in control rats. These parameters for DL-propranolol were decreased significantly in both control and uremic rats receiving injection of the uremic serum. The PSu values in both of the control and uremic rats injected with either control or uremic rat serum were significantly higher than those in rats injected with the buffer solution, suggesting the presence of a protein-mediated transport mechanism; that is, the conventional assumption that the fraction of the drug which is available for the uptake in vivo is equal to the unbound fraction as measured in vitro may not hold. In contrast, the brain extraction of D-[14C]glucose, [3H]inulin and [3H]water, which show no binding to serum protein, was not affected by the coinjection of either control or uremic rat serum. On the other hand, using either the ultrafiltrate from serum (control and uremic) or supernatant fraction from heat-treated serum (control and uremic) as the injection solution, no significant difference in the PSu value for DL-propranolol was observed between control and uremic serum. These results suggest that (1) the decrease in the PSu value for DL-propranolol in uremic rats may be attributed mainly to the presence of an endogenous inhibitory substance(s) for the brain uptake or to the decrease in the exchangeable fraction in vivo in the uremic serum; (2) the decrease in the PSu value for DL-propranolol may also be partly attributed to the change in the BBB permeability and/or surface area; (3) the inhibitor for the brain uptake may be characterized as a temperature-sensitive and nonfiltrable substance(s) at physiological pH; and (4) the ability of protein-mediated transport for DL-propranolol into brain was decreased in uremic rats.

Acute Kidney Injury↗
PubMed1989

Tissue selectivity of propranolol derivatives in vivo. A confirmation of in vitro findings.

The beta-adrenergic antagonist activities of a p-toluidide and a p-trifluoromethylanilide derivative of propranolol were tested in intact rats to determine whether the unusual in vitro profiles on myocardium and adipose tissue were found in vivo. The relative potencies of p-toluidide derivatives studied in pithed rats were 1.3 for the rate of change in left ventricular pressure with respect to time (dP/dt) and 4.6 for heart rate (HR) compared to propranolol. The values for p-trifluoromethylanilide were 2.5 (dP/dt) and 4.6 (HR). The SR-isomer of the p-toluidide derivative was 81 times more potent than propranolol in inhibiting effects on dP/dt and 27 times more effective than propranolol on HR, whereas the SS-isomer was 0.17 times (dP/dt) and 0.16 times (HR) as potent as the parent compound. In fasted rats, infusion of isoproterenol resulted in an increase of 10.6 +/- 3.1 mg/dl in plasma non-esterified fatty acid (NEFA) and an increase of 46 +/- 9 mg/dl in glucose. Unlike propranolol, neither the p-toluidide nor the p-trifluoromethylanilide derivative blocked the increase in plasma NEFA, although they both blocked the increase in plasma glucose. It appeared that the p-toluidide and p-trifluoromethylanilide derivatives of propranolol were more selective for the beta 1-adrenergic receptors on the heart as opposed to the beta 1-like adrenoceptors on adipose tissue. These findings were qualitatively and generally quantitatively in agreement with our previous findings in vitro. Therefore, the in vitro data may be useful in predicting atypical and tissue selective in vivo effects of these types of compounds.

Adipose Tissue↗