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PubMed1985

Diltiazem and propranolol, alone and in combination, on exercise performance and left ventricular function in patients with stable effort angina: a double-blind, randomized, and placebo-controlled study.

Diltiazem and propranolol alone and in combination as antianginal agents were compared with placebo in 12 patients with stable exertional angina at Stanford University Medical Center. The patients performed symptom-limited, multi-stage upright bicycle ergometric exercise while undergoing radionuclide angiographic studies every two weeks while being treated with 90 mg of diltiazem four times daily, 60 mg of propranolol four times daily, a combination of 90 mg of diltiazem and 60 mg of propranolol four times daily, and placebo. Diltiazem, propranolol and a combination all significantly increased exercise duration compared to placebo (526 +/- 149, 525 +/- 115, and 549 +/- 129 vs 430 +/- 132 sec.). Although rate pressure product and heart rate decreased with diltiazem therapy at submaximal workloads, these values were unchanged at peak exercise in contrast to propranolol or the combination of propranolol or diltiazem. Diltiazem decreased the sub-maximal and maximal degree of exercise-induced ST segment depression by over 50% compared to placebo (P less than 0.01 vs placebo). Diltiazem resulted in a higher exercise left ventricular ejection fraction compared to placebo, propranolol or the combination of diltiazem or propranolol (all less than P less than 0.05). Sinus bradycardia or orthostatic hypertension occurred in four patients on the high-dose combination therapy and required dose reduction. We concluded that high-dose diltiazem, appeared to be even more effective than moderate-dose propranolol or the combination of diltiazem and propranolol in improving exercise tolerance, electrocardiographic evidence of myocardial ischaemia and left ventricular function in patients with stable effort angina due to occlusive coronary artery disease.

Aged↗
PubMed1975

Comparative study of the effects of propranolol and tetracaine on cation movements in resealed human red cell ghosts.

1. The effects of two positively charged local anaesthetic amines, tetracaine and propranolol, on cation permeability were studied in resealed human red cell ghosts prepared from metabolically depleted erythrocytes. 2. The K permeability was reduced by tetracaine but increased by propranolol. The effect of tetracaine was independent of extracellular Ca concentration but was raised to 2-5 x 10(-7) M. The effect of propranolol, which was enhanced when the external Ca concentration was raised, could be completely inhibited by lowering the internal free Ca to less than 10(-7) M. 3. Propranolol, but not tetracaine, increased the intracellular Ca ion concentration by releasing up to 20% of the membrane-bound Ca to the cell interior. This increase in intracellular Ca was sufficient to mediate the observed change in K permeability. 4. Tetracaine and propranolol reduced the Ca binding capacity of the ghost membrane by about 20 and 40% respectively. The Ca permeability was increased by propranolol and was slightly reduced by tetracaine. 5. In high concentrations (2-7 mM) propranolol by itself moderately increased K and Na permeability, but supressed completely the Ca-induced increase in K permeability. Tetracaine in concentrations up to 4 mM enhanced the Ca-induced increase in K permeability. Higher concentrations of the drug caused lysis of the cells. 6. Maximally effective concentrations of tetracaine and propranolol inhibited the ATP-dependent Ca outward transport by 30 and 70% respectively. 7. The effects of tetracaine on K permeability were shared by the local anaesthetics prilocaine and lidocaine, those of propranolol were shared by practolol, a beta-adrenergic antagonist and tetraethylammonium, a ganglionic blocking agent. 8. It is suggested that the differences in the effects of tetracaine and propranolol on cation permeability reflect qualitatively different interactions of the two drugs with Ca binding sites on the inner surface of the membrane.

Adenosine Triphosphate↗
PubMed2003

Potent antioxidant properties of 4-hydroxyl-propranolol.

The antioxidant properties of 4-HO-propranolol (4HOP), a major metabolite of propranolol, were studied and compared with that of propranolol and vitamin E (Trolox). When isolated hepatic microsomal membranes were peroxidized by an iron-catalyzed.OH-generating system [dihydroxyfumarate +Fe (III)], 4HOP potently and concentration-dependently inhibited lipid peroxidation; the IC50 value was 1.1 microM, whereas those for Trolox and propranolol were 4.3 and 168 microM, respectively. When isolated human low-density lipoprotein (LDL) was oxidized by 7.5 microM Cu(II) for 9 h, 4HOP at 3 microM delayed the lag phase significantly by 108 min, which was comparable with that of probucol (98-min delay) but was far greater than that provided by propranolol (6 min) or Trolox (47 min). At 1 microM 4HOP, the delay was 45 min. When confluent cultured bovine aortic endothelial cells were exposed to the Fe-catalyzed oxy-radical system, acute loss of glutathione occurred (55% decrease in 50 min). Pretreatment of the cells with 0.067 to 6.7 microM 4HOP for 30 min provided increasing degrees of protection against the glutathione loss; the EC50 value was 1.2 microM, whereas those for Trolox and propranolol were 7.9 and 49 microM, respectively. The loss of cell survival due to the radical stress was also effectively preserved by 4HOP. In separate experiments, when the endothelial glutathione was oxidatively depleted by a peroxynitrite-generating system (3-morpholinosydnonimine), 4HOP also provided potent protective activities. In conclusion, 4HOP is 4- to 8-fold more potent than vitamin E and >100-fold more active than propranolol as a "chain-breaking" antiperoxidatant against membrane and LDL oxidation and can provide superior endothelial cytoprotective efficacy against oxygen- or nitrogen-derived oxidant-mediated cell injury. Being a major metabolite in human and with its plasma level approaching that of propranolol, 4-HO-propranolol may contribute, in part, to the cardiovascular therapeutic benefits of propranolol.

Animals↗
PubMed1989

Propranolol antagonizes hypotension induced by alpha-blockers but not by sodium nitroprusside or methacholine.

A pressor response has been observed with propranolol, a nonselective beta-adrenoceptor antagonist, in animals given a nonselective alpha-adrenoceptor antagonist. This study investigates whether a pressor response to propranolol occurs in conscious unrestrained rats following a hypotensive response induced by phentolamine (nonselective alpha-antagonist), prazosin (selective alpha 1-antagonist) and (or) rauwolscine (selective alpha 2-antagonist), sodium nitroprusside (smooth muscle relaxant), or methacholine (muscarinic agonist). The rats were subjected to a continuous infusion of a hypotensive agent or normal saline followed by i.v. injection of propranolol. The infusion of phentolamine significantly decreased mean arterial pressure (MAP). Subsequent injection of propranolol restored MAP to the control level. Prazosin and rauwolscine each caused a small but not significant decrease in MAP which was reversed by propranolol. Concurrent infusions of prazosin and rauwolscine caused a significant decrease in MAP. Subsequent injection of propranolol caused a large pressor response which increased MAP to 20% above control MAP prior to the administration of drugs. Nitroprusside or methacholine each caused a significant decrease in MAP, but the hypotension was not antagonized by propranolol. The concurrent infusions of a low dose of nitroprusside and prazosin caused a significant decrease in MAP which was reversed by propranolol. The infusion of saline did not alter MAP, and propranolol did not cause a pressor response. It is concluded that propranolol antagonizes the hypotensive effect of an alpha-blocker but not that of sodium nitroprusside or methacholine. Our results suggest the presence of a specific interaction between alpha- and beta-antagonists.

Adrenergic alpha-Antagonists↗
PubMed1983

Cardiac sarcolemmal Na+-K+-ATPase: combined effects of propranolol and arachidonyl CoA.

Sarcolemma from adult canine cardiac myocytes (Na+-K+-ATPase activity 71.8 +/- 3.4 mumol . mg protein-1 . h-1) was preincubated (10 min at 37 degrees C, pH 7.2) with 1) 5-250 microM arachidonyl CoA, 2) 2.5 nM- 2.5 mM propranolol, 3) 5-250 microM arachidonyl CoA plus 2.5 mM propranolol or 4) 2.5 nM-2.5 mM propranolol plus 50 microM arachidonyl CoA; after preincubation the Na+-stimulatable activity was assayed. Arachidonyl CoA alone (50 microM, expt 1) elicited maximum stimulation (89% above control), whereas concentrations greater than 125 microM were inhibitory. Preincubation with propranolol alone (expt 2) had no significant effect on activity. However, when membranes were pretreated with both arachidonyl CoA and 2.5 mM propranolol (expt 3) activity was significantly inhibited. Preincubation with concentrations of propranolol greater than 25 microM were required to reverse the stimulatory effect of 50 microM arachidonyl CoA (expt 4). Propranolol and arachidonyl CoA do not have to be present simultaneously to produce an inhibitory effect. Activity was greatly inhibited (87%) when membranes were preincubated with 100 microM arachidonyl CoA followed by addition of 2.5 mM propranolol; no inhibition was observed if preincubation conditions were reversed. These data suggest that propranolol-induced inhibition of the Na+-K+-ATPase is reversible but becomes irreversible when sarcolemma is pretreated with the fatty acyl CoA, either prior to or during propranolol preincubation.

Acyl Coenzyme A↗
PubMed1975

Plasma and atrial propranolol after preoperative withdrawal.

Of 34 patients scheduled for aortocoronary bypass operations who were withdrawn from chronic propranolol therapy between 18 and 48 hours before anesthesia and operation, propranolol was detected in the plasma of nine and in atrial tissue of five patients. Higher plasma levels were associated with higher propranolol intake and with shorter time of withdrawal. In 15 patients withdrawn preoperatively from propranolol the heart rate and blood pressure response to 3 mug isoproterenol was not significantly different from the response of similar patients who had received no propranolol. In contrast to the response of healthy subjects, most patients with coronary artery disease responded to isoproterenol with a decrease in systolic blood pressure. Plasma propranolol levels after a 0.5 mg bolus given intravenously during operation produced a peak level of 40 ng/ml in one minute and disappeared in five minutes. These studies suggest that no beta blockade persists 18 hours after acute preoperative withdrawal of propranolol in patients taking up to 300 mg per day for control of angina. In view of the reported hazards of abrupt withdrawal of propranolol before operation and the reported usefulness of propranolol in treating tachyarrhythmias during operation, we suggest that early preoperative withdrawal of propranolol may be more hazardous than its continuation before coronary bypass operations.

Angina Pectoris↗
PubMed1983

Effects of propranolol on reflex vascular responses to orthostatic stress in humans. Role of ventricular baroreceptors.

To evaluate the role of ventricular baroreceptors in humans, we studied the effects of propranolol on reflex vasoconstrictor responses to simulated orthostatic stress. We measured forearm vascular resistance in 10 normal males in the control state and during lower body negative pressure (LBNP) at -10 and -40 mm Hg before and after propranolol (0.1 mg/kg i.v.). Baseline forearm vascular resistance showed no significant change: 23.9 +/- 3.4 U (+/- SEM) before vs 28.0 +/- 0.5 U after propranolol. Reflex increases in forearm vascular resistance during LBNP at -10 and -40 mm Hg were 5.2 +/- 1.2 and 21.2 +/- 6.6 U before and 3.4 +/- 1.2 and 10.6 +/- 2.2 U, respectively, after propranolol. Thus, propranolol significantly (p less than 0.05) reduced responses to LBNP at -40 mm Hg. In contrast to the effects with LBNP, propranolol did not attenuate increases in forearm vascular resistance during the cold pressor test and handgrip, thus excluding a nonspecific depression of reflexes. We also studied the effects of propranolol on carotid baroreflex-mediated vasoconstrictor responses to neck pressure at 15 and 30 mm Hg. Propranolol had no significant effect on the vasoconstrictor responses to neck pressure. In conclusion, propranolol selectively attenuates vasoconstrictor responses to LBNP. We suggest that this results from a propranolol-induced decrease in the activity of cardiac ventricular baroreceptors. The results support the view that ventricular baroreceptors play an important role in reflex adjustments to orthostatic stress in humans.

Adult↗
PubMed1985

Superiority of combined diltiazem and propranolol therapy for angina pectoris.

Twenty-four patients with stable angina were evaluated in a 14 week crossover trial. A single-blind placebo period (baseline 1) was followed by two double-blind periods evaluating maximum tolerated doses of diltiazem (up to 360 mg daily) vs placebo. Over the next 1 to 4 weeks, propranolol was started and increased until clinically documented beta-blockade was achieved (baseline 2). The final phase consisted of a pair of evaluation periods comparing propranolol plus the maximum tolerated dose of diltiazem to propranolol and placebo. The daily rate of angina attack was 1.6 during baseline, was unchanged during placebo therapy, but fell during treatment with diltiazem to 0.6 (p less than .005). With the addition of diltiazem to propranolol, the angina rate was improved (0.3) compared with that with either propranolol alone (0.6) or propranolol and placebo (0.5) (p less than .01). Total exercise duration during baseline 1 was 360 sec and increased to 497 sec with diltiazem, 481 sec with propranolol, and 527 sec with the combination of diltiazem and propranolol. Two patients with reduced ejection fractions developed congestive heart failure with propranolol. The combination of diltiazem and propranolol similarly resulted in congestive heart failure in one patient who had tolerated both drugs alone.

Aged↗
PubMed1986

Effect of the addition of propranolol to therapy with nifedipine for unstable angina pectoris: a randomized, double-blind, placebo-controlled trial.

The value of the addition of beta-blockers to coronary vasodilator therapy in the treatment of patients with unstable angina at rest is controversial. We conducted a double-blind, randomized, placebo-controlled 4 week trial of propranolol in 81 patients with unstable angina, 39 of whom were assigned to placebo and 42 of whom received propranolol in a dose of at least 160 mg daily. All patients were also treated with coronary vasodilators, including 80 mg nifedipine daily and long-acting nitrates. The incidences of cardiac death, myocardial infarction, and requirement for bypass surgery or coronary angioplasty did not differ between the two groups (propranolol = 16; placebo = 18). The propranolol group had a lower cumulative probability of experiencing recurrent resting angina than the placebo group (p = .013), and over the first 4 days of the trial the mean number of clinical episodes of angina (propranolol 0.9 +/- 0.2, placebo 1.8 +/- 0.3, p = .036), duration of angina (propranolol 15.1 +/- 4.3 min, placebo 38.1 +/- 8.4, p = .014), and nitroglycerin requirement (propranolol 1.1 +/- 0.3 tablets, placebo 3.5 +/- 0.8, p = .003) were also fewer. Continuous electrocardiographic recording for ischemic ST segment changes revealed fewer daily ischemic episodes in the propranolol group (2.0 +/- 0.5) than in the placebo group (3.8 +/- 0.7, p = .03), and a shorter duration of ischemia (propranolol 43 +/- 10 min, placebo 104 +/- 28 min, p = .039). Thus propranolol, in patients with unstable angina, in the presence of nitrates and nifedipine is not detrimental and reduces the frequency and duration of symptomatic and silent ischemic episodes.

Adult↗
PubMedDate not supplied

A possible antihypertensive mechanism of propranolol: antagonism of angiotensin II enhancement of sympathetic nerve transmission through prostaglandins.

The effects of propranolol on angiotensin II (AII) enhancement of sympathetic nerve transmission were investigated in the in situ blood-perfused mesenteric vascular bed of the rat. Angiotensin II in subpressor concentrations (3 ng/ml) potentiated the vasoconstrictor responses to both sympathetic nerve stimulation (NS) and exogenous norepinephrine (NE). The dl-propranolol had no effect on the basal vasoconstrictor responses to NS and NE, yet inhibited the AII-enhanced vasoconstrictor responses to NS by 47% (p less than 0.05) and 81% (p less than 0.001) at 100 and 300 ng/ml respectively. In contrast, the potentiation of NE responses by AII was unaffected by propranolol. A similar blockade of AII enhancement of NS was observed with the d-isomer of propranolol. Dibucaine (300 ng/ml), a local anesthetic, failed to alter the basal or AII-enhanced responses to either NS or NE. Indomethacin, a prostaglandin synthetase inhibitor (5 mg/kg, s.c.), abolished the inhibitory effect of dl-propranolol on AII enhancement of NS. Prostaglandin E2 (PGE2), but not prostaglandin I2, (3 ng/ml) inhibited AII enhancement of NS without altering the basal response to NS or NE in indomethacin-pretreated animals. Intraarterial infusions of dl-propranolol, d-propranolol, AII, and dl-propranolol-plus-AII into the superior mesenteric artery increased mesenteric venous PGE2 concentrations from 216 +/- 33 to 355 +/- 33 (p less than 0.01), 328 +/- 44 (p less than 0.05), 325 +/- 27 (p less than 0.02), and 407 +/- 44 pg/ml (p less than 0.01) respectively. We conclude that propranolol antagonizes AII enhancement of NS by increasing prostaglandin levels in vascular tissue. Furthermore, these findings suggest that propranolol may exert its antihypertensive effect through the release of prostaglandins when used in therapeutic doses in excess of those required for beta-adrenergic blockade.

Angiotensin II↗
PubMed1985

Effects of propranolol on atherogenesis in the cholesterol-fed rabbit.

These studies have examined the effects of dl-propranolol, d-propranolol, and metoprolol on aortic atherogenesis in the cholesterol-fed rabbit and have correlated the vascular effects of the drugs with their influence on blood pressure, plasma lipids and lipoproteins, arterial metabolism, and arterial permeability. dl-Propranolol, and, to a lesser extent, d-propranolol, used in clinically relevant doses of 5 mg/kg body weight per day, inhibited the development of aortic atherosclerosis in association with significant reductions in aortic free and esterified cholesterol content. No significant effects of the drugs on blood pressure or on the total amounts or types of circulating lipoproteins were apparent. Accumulation of cholesterol in the liver and adrenal gland was not influenced by propranolol. Aortic acyl CoA:cholesterol acyltransferase and lysosomal enzyme activities were reduced by propranolol administration, but the inhibition may have been secondary to the lesser degrees of atherosclerosis and cholesterol accumulation present. In vitro inhibition of acyl CoA:cholesterol acyltransferase activity by either dl- or d-propranolol was also observed, but occurred only at propranolol concentrations of 10(-3) M or greater. Treatment with dl-propranolol had no significant effect on the rate of transport of labeled albumin across the isolated carotid artery of cholesterol-fed rabbits. Metoprolol administration (6.25 mg/kg body weight per day) had no significant influence on atherogenesis or arterial metabolism in this model. The results suggest that propranolol inhibits in part the development of atherosclerosis in the cholesterol-fed rabbit, and that the effect may be related to a direct action on the arterial wall.

Animals↗
PubMed1992

Mechanisms of pharmacokinetic interaction between propranolol and quinidine in rats.

In order to study the mechanism of propranolol-quinidine interaction, the effects of quinidine on propranolol pharmacokinetics were examined in male Wistar rats. The concurrent oral administration of quinidine (10 mg/kg) markedly increased the plasma concentration of propranolol (2.5 mg/kg), and the area under the propranolol concentration-time curve increased about 3.6-fold. These results are consistent with previous observations in man and indicate the possible usefulness of the male Wistar rat as an animal model for investigating the mechanisms of the drug interaction. When propranolol was given intravenously, a concurrent administration of quinidine increased the apparent distribution volume of propranolol, mainly by decreasing its plasma protein binding. However, the systemic clearance of propranolol was not significantly altered by quinidine. Thus, quinidine increased the availability of oral propranolol from 13.8 +/- 2.2 to 44.2 +/- 4.6% (p less than 0.01). Furthermore, quinidine delayed the elimination of propranolol from the isolated perfused rat liver. These results indicate that quinidine reduces the presystemic elimination of propranolol in the liver, thereby increasing its systemic availability after oral administration.

Animals↗
PubMed1982

Effects of propranolol on perceived exertion soon after myocardial revascularization surgery.

Effect of propranolol on perceived exertion soon after myocardial revascularization surgery. Med. Sci. Sports Exercise. Vol. 14, No. 4, pp. 276-280, 1982. This study evaluated the effects of propranolol on ratings of perceived exertion (RPE), heart rate (HR), and systolic blood pressure (SBP) during graded exercise testing of myocardial revascularization surgery patients before hospital discharge. Eighty-six men performed a symptom-limited, graded exercise test on a treadmill an average of 11 d after surgery. Patients were assigned to three groups: those not taking propranolol (no-propranolol group, N = 54), those taking propranolol (propranolol group, N = 22), and those exhibiting exertional hypotension during testing (hypotensive group, N = 10). Test results showed that estimated METs during peak exercise were similar for the three groups. The propranolol group demonstrated a lower HR for submaximal and peak exercise when compared with the no-propranolol group, but RPE was the same for matched exercise intensities. The hypotensive group failed to increase SBP during exercise, but perceived the matched exercise intensities to be the same as the other two groups. The HR response of the hypotensive group was similar to that of the no-propranolol group. Thus, an abnormal SBP response during exercise was not reflected in a changed RPE when compared with patients who increased SBP appropriately. It was concluded that propranolol does not affect RPE during graded exercise testing soon after cardiac surgery.

Adult↗
PubMed1988

Relationship among beta-adrenergic blockade, propranolol concentration, and liver function in patients with cirrhosis.

In 20 patients with cirrhosis we studied the relationship among the efficiency of beta-adrenergic blockade induced by oral administration of 40 mg propranolol, the plasma level of propranolol, and the liver function. The beta-adrenergic blockade was studied 2 h and 8 h after propranolol administration and assessed by the cardiac chronotropic response to isoprenaline. Liver function was evaluated by a standard liver function test and the Child-Turcotte or Pugh score. The beta-adrenergic blockade and propranolol plasma concentration were higher 2 h than 8 h after propranolol administration. The beta-adrenergic blockade and the propranolol plasma concentration varied widely among patients. No significant correlation was found between the efficiency of beta-blockade and propranolol concentration. The beta-adrenergic response before propranolol administration was correlated with bilirubin level and Child scores, but no significant correlation was found between the beta-blockade and the severity of liver disease. These results suggest that in patients with cirrhosis, differences in response to propranolol are not related to differences in the severity of the liver disease or to differences in propranolol concentration.

Female↗
PubMed2004

[Effects of microsome enzyme induced by phenobarbarbital on the stereoselectivity of recemic propranolol glucuronidation metabolism].

OBJECTIVE: To study the stereoselectivity of R-(+) and S-(-)-propranolol glucuronidation and metabolic interaction between R(+)- and S-(-)-propranolol. METHODS: A RP-HPLC analytical method was developed for determination of R-(+)-and S-(-)-propranolol glucuronide (PG) incubated with rat hepatic microsome induced with phenobarbital (PB). The method was applied to investigate the stereoselectivity metabolism of racemic propranolol glucuronidation in vitro. RESULT: In control and PB group, the concentration of R-(+)-PG produced at different substrates was higher than that of S-(-)-PG. Compared with the control, the V(max) and Cl(int) for R(+)-and S-(-)-propranolol increased significantly the K(m) for R(+)-propranolol was elevated, while that for S-(-) propranolol was decreased. CONCLUSION: There is a stereoselectivity in glucuronidation of propranolol in rat hepatic microsome induced with PB and R-(+)-propranolol is preferred. Metabolic interaction between R-(+)-and S-(-)-propranolol exists with a concentration-dependent mode.

Animals↗
PubMedDate not supplied

The formation of glutathione conjugate derived from propranolol.

Mixed function oxidases in liver microsomes from 3-methylcholanthrene-pretreated guinea pigs converted S-propranolol to 4-hydroxypropranolol, 5-hydroxypropranolol, and desisopropyl-propranolol. The addition of glutathione and cytosol from rat liver to the system resulted in the formation of a water-soluble metabolite. Evidence that the metabolite was a glutathione adduct was obtained by showing that treatment with gamma-glutamyltranspeptidase changed its HPLC retention time. The formation of the glutathione adduct required glutathione S-transferases in cytosol and was accompanied by a decrease in the formation of 5-hydroxypropranolol, but not of 4-hydroxypropranolol or desisopropylpropranolol. The formation of the propranolol-glutathione adduct was confirmed by two independent approaches. When [14C]glutathione and [3H]S-propranolol were used, the relationship between 14C and 3H in the metabolite indicated that it contained equal amounts of glutathione and propranolol. When a pseudoracemic mixture of S-propranolol and [2,4-2H2]R-propranolol was used, thermospray LC/MS analysis of the glutathione adduct revealed two peaks having different retention times. The first peak, representing a [2,4-2H2]R-propranolol-GSH adduct, gave fragment ions at m/z 294, 278, 262, while the second, which represented the S-propranolol-GSH adduct, gave fragment ions having 2 mass units less than those obtained with [2,4-2H2]R-propranolol. There was no evidence of any loss of deuterium during the formation of these fragment ions. The material in both peaks gave ions of m/z 308, 147, and 130, which is consistent with the presence of a glutathione group.

Animals↗
PubMed1987

Attenuation by propranolol of exercise training effects in spontaneously hypertensive rats.

The effects of propranolol (10 mg/kg) on systolic blood pressure (SBP), resting and exercising heart rates (HR), and body weight (BW) were examined in 11-week swim-trained spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. In both species, SBP was significantly reduced by either propranolol or training, but the reduction was greater with propranolol than with training. However, when propranolol was administered to rats during training, their independent beneficial effects on SBP were annulled. HR was modified slightly by propranolol and training, but they both decreased BW. The mechanism of propranolol action on BW is not clear. Maximum oxygen uptake (VO2 Max), relative heart weight (RHW), and absolute heart weight (AHW) were measured after 11 weeks of training. In both SHR and WKY rats, VO2 Max was elevated by exercise training; moreover, VO2 Max was greatest among those receiving propranolol while training. However, the combined effects of propranolol and training produced a significant reduction of AHW in SHR. The RHW was increased by training, but it was decreased by propranolol. SHR rats were more sensitive to the effects of training and propranolol than WKY rats. In humans, several observations have been reported on the attenuation of certain exercise-induced cardiovascular and metabolic changes by beta-adrenergic blocking agents. Our results obtained with rats confirm some of those observations. It would seem that the hypertensive strain of rats could serve as a model for the study of attenuation mechanisms by beta-adrenergic blockers.

Animals↗
PubMedDate not supplied

Propranolol-induced depression and psychosis.

Episodes of depression and acute psychosis in two patients receiving propranolol hydrochloride are described, and the literature on propranolol-induced depression and psychosis is reviewed. A 42-year-old woman developed severe depression, marked apathy, social withdrawal, and anorexia after taking propranolol hydrochloride (80 mg/day) for three months to control her hypertension. Five days after the dose was reduced to 40 mg/day, there was a major improvement in her depressive symptoms, with a complete resolution in eight days. Upon rechallenge with 80 mg/day of propranolol, she again experienced depressive symptoms. Atenolol 50 mg/day was substituted for the propranolol therapy, and she exhibited a complete remission of her depression. The second patient was a 63-year-old man who had been taking propranolol hydrochloride 160 mg/day for three months without incident. Because of an increased frequency of anginal attacks, the dosage was increased to 240 mg/day. Within two days, he demonstrated such agitation, excitement, and combativeness that he had to be controlled with a 25-mg dose of methotrimeprazine. When the propranolol dose was reduced to 160 mg/day, his psychotic symptoms rapidly cleared. However, when the dose was subsequently increased to 200 mg/day, he again showed increased agitation. After substituting atenolol 100 mg/day for propranolol, the patient's mental status returned to normal. Both of these patients experienced symptoms that were temporarily associated with propranolol. Both patients were subsequently controlled without symptoms with atenolol therapy. Propranolol is a highly lipophilic beta blocker that achieves high concentrations in the brain. When continued beta-blocking therapy is necessary or beta blockade is indicated, a weakly lipophilic agent such as atenolol is indicated.

Adult↗