Effects Of Beta-adrenoceptor Blockade Research Articles

Effect of Beta-Adrenergic Blockade and Sympathetic Stimulation on Canine Bronchial Mast Cell Response to Immune DegranulationIn Vivo

We examined the effect of beta-adrenoceptor blockade and residual alpha-adrenoceptor effects during sympathetic stimulation on mast cell secretion of histamine in 12 natively allergic mongrel dogs. Bronchial mast cell response was measured as the arteriovenous difference (AVd) in plasma histamine concentration [H] across the bronchus. Plasma [H] was determined simultaneously from the azygos outflow tract and femoral artery as a marker of mast cell response prior to and for 90 s after intra-arterial injection of sham diluent and 1:100 and 1:30 dilutions of Ascaris suum antigen. Sympathetic (alpha-adrenergic) stimulation was elicited with continuous infusion of the nicotinic agonist, dimethylphenylpiperazinium (DMPP) under conditions of muscarinic blockade with atropine and beta-adrenoceptor blockade with propranolol. Plasma epinephrine (EPI) increased from 315 +/- 106 to 34,127 +/- 10,711 pg/ml (p less than 0.02). Control animals receiving sham infusion in place of sympathetic stimulation additionally had neural blockade with hexamethonium and alpha-adrenoceptor blockade with phentolamine. Plasma EPI was 90 +/- 58 pg/ml and did not change significantly during mast cell degranulation. Significant AVd in [H] was elicited after 1:30 A. suum antigen in both control (72.9 +/- 12.5 ng/ml versus 2.8 +/- 10.1 ng/ml at baseline; p = 0.031) and beta-adrenergically blocked (alpha-stimulated) (106.1 +/- 20.1 versus -1.5 +/- 35.9 ng/ml at baseline; p = 0.031) animals. However, alpha-adrenoceptor stimulation did not elicit significantly augmented secretion of [H]. We demonstrate that beta-adrenoceptor blockade blocks completely the inhibition of mast cell secretion caused by sympathetic stimulation with DMPP. However, alpha-adrenoceptor stimulation does not cause significant augmentation of mast cell secretion in the large airways of the dog.

Effect of beta-adrenergic receptor blockade on responses to acute hypoxemia in lambs.

We studied the effects of beta-adrenergic receptor blockade on general circulatory and metabolic responses to moderate (FIO2 = 0.09) acute hypoxemia in newborn (protocol 1) and 3-wk-old (protocol 2) lambs, and on regional blood flow distribution in newborn lambs (protocol 1). Via a left thoracotomy we placed an electromagnetic flow transducer around the ascending aorta and inserted various vascular catheters. After 2 days of recovery, the lambs were studied. In protocol 1, we measured cardiovascular variables and regional blood flow distribution during control conditions, after 45 min of acute hypoxemia, and after 0.5 mg/kg of propranolol during acute hypoxemia. In protocol 2, we measured cardiovascular variables during control conditions and after 45 min of acute hypoxemia with and without propranolol pretreatment. In both groups, propranolol limited the increase in cardiac output and heart rate caused by hypoxemia, and thus decreased oxygen delivery. However, propranolol also decreased oxygen consumption so that pulmonary arterial pO2 was either higher (protocol 1) or the same (protocol 2) as during acute hypoxemia alone. Neither metabolic acidosis nor hypothermia ensued. In protocol 1, propranolol decreased renal, carcass, and most importantly, myocardial blood flows. However, myocardial O2 consumption also fell, coronary sinus pO2 increased, and blood was redistributed toward the subendocardium, suggesting that myocardial perfusion improved. Thus, beta-adrenergic receptor blockade during acute moderate hypoxemia may have a beneficial effect by reducing total body and myocardial oxygen demand in excess of the reduction in oxygen delivery.

Effects of β-Receptor Blockade on Regional Blood Flows During Acute Left Ventricular Failure in Dogs

This study describes the effects of beta-receptor blockade on systemic hemodynamics and regional blood flows during acute ischemic heart failure in dogs. Depression of left ventricular (LV) function was induced by embolization of the left main coronary artery and was evidenced by a significant increase in LV end-diastolic pressure (LVEDP) and decrease in LV dP/dtmax and in cardiac output. Measurements of femoral, renal, mesenteric, and carotid blood flows showed a redistribution of cardiac output during failure. Femoral blood flow decreased to a greater extent than did cardiac output, carotid blood flow decreased in proportion to cardiac output, whereas mesenteric and renal blood flows were moderately reduced in relation to the decrease in cardiac output. Administration of 0.125 mg of propranolol intravenously (i.v.) significantly decreased the performance of the failing left ventricle. Reductions in cardiac output were accompanied by reductions in the peripheral circulations. The decrease in flow was evenly distributed in the femoral, mesenteric, and carotid vascular beds, while there was a relative preservation of renal blood flow. When the dose of propranolol was increased to 0.5 mg/kg, there were no further significant hemodynamic alterations.

Hemodynamic Effects at Rest and During Exercise of Combined α/β-Receptor Blockade and of β-Receptor Blockade Alone in Patients with Ischemic Heart Disease

The acute hemodynamic responses to beta-adrenoceptor blockade with the beta 1-selective antagonist metoprolol, and to combined alpha/beta-receptor blockade with labetalol, were compared intraindividually in a randomized single-blind, cross-over study. Fourteen patients with proved ischemic heart disease, aged 52-64 years, were studied at rest (supine) and during ischemia-inducing exercise (in the seated posture) using invasive percutaneous techniques. Metoprolol reduced heart rates and cardiac output greatly (p less than 0.001) and systemic arterial pressures slightly (p less than 0.001) under all conditions. Left ventricular filling pressures increased. Labetalol induced a slight decrease in heart rates during exercise, while cardiac output was unchanged. Systemic arterial pressures and vascular resistances, pressures and resistances in the pulmonary circulation, and left ventricular filling pressures were distinctly lower. During ischemia-inducing exercise, the differences between the effects of labetalol and metoprolol on heart rate, cardiac output, systemic vascular resistance, and left ventricular filling pressures were highly significant. The effects on the rate X pressure product and on angina were similar. It is concluded that combined alpha/beta-blockade with labetalol offsets or attenuates the potential adverse hemodynamic effects of beta-receptor blockade alone without loss of symptomatic efficacy.

Effect of Beta-Adrenoceptor Blockade and Calcium Antagonism, Alone and in Combination, on Thermoregulation During Prolonged Exercise*

The effect of clinically used doses of propranolol, atenolol, nifedipine, propranolol plus nifedipine, and atenolol plus nifedipine on thermoregulatory responses of 11 healthy men was studied during 2-h block-stepping in heat. Drug intervention did not alter ventilation during exercise. In contrast, propranolol and atenolol produced equivalent reductions in exercise tachycardia, implying a similar level of beta 1-adrenoceptor blockade. The heart rate response to exercise was unaffected by nifedipine and during dual beta-adrenoceptor blockade and calcium antagonism was equivalent to that with beta-adrenoceptor blockade alone. While rectal temperature rises were not modified by drug ingestion, propranolol and, to a lesser degree, atenolol and combination therapy, but not nifedipine alone, attenuated skin temperature rises. Moreover, although atenolol, nifedipine, and their combination did not alter sweating, propranolol and its combination with nifedipine enhanced sweating during the 1st and 2nd h of exercise. This study concludes that nifedipine does not modify thermoregulation during exercise and allows for greater confidence of its use during cardiac rehabilitation. Furthermore, the present data confirm that propranolol does enhance sweating during exercise and demonstrate that this effect is not mediated simply by an earlier onset of rapid sweating nor abolished by concomitant calcium antagonism.

Adrenergic system and carbohydrate metabolism. Effects of beta-receptor blockade on insulin secretion and peripheral insulin sensitivity in normoglycaemic patients.

The effects of 3 weeks of treatment with the beta-receptor blocking agent propranolol and a placebo on glucose tolerance, insulin secretion and peripheral insulin sensitivity have been evaluated in 7 normoglycaemic hypertensive patients by an oral glucose tolerance test and the insulin clamp technique. Significant changes in systolic and diastolic blood pressure and heart rate were observed at the end of propranolol treatment, but there were no associated changes in glucose tolerance, insulin secretion or peripheral insulin sensitivity. No difference was observed in glucagon, growth hormone and free fatty acids between propranolol and placebo treatment. The results support the view that the hypothetical pancreatic glucoreceptor, at least in non-acute studies, is not affected by beta blockade. In addition, there was no effect on tissue sensitivity to insulin.

Effect of beta-adrenoceptor blockade on H+ and K+ flux in exercising humans.

The effect of beta-adrenoceptor blockade (beta B) on muscle release and uptake of H+ and K+ in humans during maximal exercise has been investigated. Eight volunteers cycled intermittently at power outputs corresponding to 100% of maximal O2 uptake. Prior to exercise either propranolol (beta B) or saline (control) was infused into the femoral vein. Arterial and femoral venous blood samples were drawn at rest, during exercise, and during 30-min recovery. Peak arterial blood values for K+, lactic acid (LA), and base deficit (BD) (mean +/- SE) were respectively 5.5 +/- 0.1, 9.5 +/- 0.6, and 11.7 +/- 0.9 mmol/l during beta B and 5.1 +/- 0.1, 8.3 +/- 0.6, and 10.3 +/- 1.0 for control (P less than 0.05). The release of K+ from the working leg did not differ between treatments during exercise, but K+ uptake during late recovery (5-30 min) was slightly lower during beta B. Thus the higher arterial K+ levels during exercise (beta B) cannot be attributed to greater release by active muscle but are likely due to decreased K+ uptake by noncontracting muscle. Arterial-femoral venous differences for LA and BD did not differ significantly between treatments. Additionally LA exchange across the leg was similar to H+ exchange (arterial-femoral venous differences for BD) under all conditions. During early recovery (1-5 min), regardless of experimental treatment, BD levels iin arterial blood were higher than LA (P less than 0.05). These elevated BD levels may be due to unequal removal rates between LA and H+ equivalents by nonexercised tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary adjustments during exercise and an aversive reaction time task: effects of beta-adrenoceptor blockade.

ABSTRACTThe purpose of this study was to compare the cardiopulmonary and hemodynamic adjustments to a physical (bicycle exercise) and behavioral (aversive reaction time) stressor. A related aim was to assess the role of beta‐adrenergic mechanisms in mediating these physiological responses. Thirty‐four subjects were exposed to both stressors while oxygen consumption, carbon dioxide production, pulmonary ventilation, end‐tidal oxygen and carbon dioxide, as well as heart rate were calculated breath‐by‐breath. Fourteen of these subjects were pretreated with 4 mg (iv) of propranolol hydrochloride. The remaining 20 subjects (intact) were subdivided post‐hoc into the 10 most and 10 least reactive on the basis of their heart rate response to the reaction time task. The results indicate that for the intact group both exercise and the reaction time task produced significant increases in heart rate although the magnitude of the heart rate change was reliably greater during exercise. Beta‐adrenergic blockade partially diminished the tachycardia to exercise but entirely abolished the tachycardia to behavioral stress. Interestingly, the most and least reactive subjects did not exhibit differential heart rate acceleration during exercise despite a reliable difference during the reaction time task. Oxygen consumption significantly increased to predictable levels during exercise but failed to change during the reaction time task for both the most and least reactive groups. These results suggest that the tachycardia elicited by the reaction time task in reactive subjects was not associated with an appropriate increase in oxygen consumption, relative to exercise, and may therefore be indicative of systemic overperfusion.

Tolerance to heat of rats treated by β-blocker. Rôle of submaxillary salivary glands

Effect of beta-adrenoceptor blockade on the changes in rectal temperature (RT), heat production (HP) and noradrenaline (NA) concentration in the submaxillary salivary glands (SMSG) of rats exposed to heat (45 degrees C) was studied. Propranolol (P) (15 mg/kg i.p.) decreased the tolerance to heat. The survival time of propranolol-treated (PT) rats was 30 min shorter. The temperature curve of control rats exposed to heat can be divided into three phases: a rapid rise in RT; a plateau (TP) and a prelethal increase. In PT animals, under identical conditions, TP disappears and RT further rises accelerating death. In the initial phase of heat exposure, HP was markedly decreased to the same extent in both experimental groups; but after 20 min HP increases in PT rats. The content of NA from SMSG both in the initial phase and in the TP phase is modified in PT rats.

Effects of beta-adrenoceptor blockade on exercise performance and respiratory response in healthy, physically untrained humans.

The effects of propranolol 80 mg orally were compared with those of placebo on the response to a stepwise increasing exercise test in 17 healthy and physically untrained volunteers, of whom eight were female. Propranolol showed no significant effects on maximum work rate or perceived exertion rate. However, submaximal O2 uptake, CO2 output and minute ventilation tended to be lower after propranolol than after placebo. It is concluded that in subjects with a low work capacity, beta-adrenoceptor blockade does not impair maximal exercise capacity. The mechanisms underlying changes in respiratory response to exercise after propranolol are not fully explained. However, changes in substrate utilisation, the reduction in cardiac output and an alteration in respiratory drive may all be involved.

Effects of short term beta adrenoreceptor blockade on serum lipids and lipoproteins in patients with hypertension or coronary artery disease.

The effects of beta adrenoceptor blockade with propranolol or pindolol on serum total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and its subfractions HDL2 and HDL3, serum triglyceride, and Intralipid clearance were studied in 17 normolipidaemic, non-diabetic patients with hypertension or angina pectoris. Both pindolol and propranolol had similar effects on fasting serum total and lipoprotein cholesterol concentrations. HDL2 cholesterol concentrations were reduced by 9 +/- 29% and HDL3 cholesterol increased by 11 +/- 16%, but there were no significant changes in total or LDL cholesterol in the combined groups after six weeks' treatment. After 12 weeks' treatment total cholesterol concentrations were reduced by 7 +/- 10% mainly owing to a reduction in the LDL fraction of 9 +/- 15%. Concentrations of HDL2 remained low, 8% less than control values. Serum triglyceride concentrations were increased by both drugs at six weeks but had returned to base values in the pindolol group by the twelfth week. Pindolol, but not propranolol, enhanced the rate of clearance of intravenous Intralipid.

The effects of beta adrenoceptor blockade with atenolol on myocardial cellular and subcellular hypertrophy in spontaneously hypertensive rats.

In this study we investigated the effects of chronic beta adrenoreceptor blockade with atenolol on cellular and subcellular hypertrophy in spontaneously hypertensive rats (SHR). Atenolol was injected subcutaneously (20 mg/kg) twice daily commencing in four-week-old rats. The treated animals (SHR-A) were compared to their nontreated controls and normotensive, Wistar-Kyoto (WKY) controls at the age of 16 weeks. A group of atenolol-treated WKY was also studied. Chronic drug treatment was effective in attenuating the rise in systolic blood pressure characteristic of SHR, but did not normalize the values to those of WKY. Cardiac hypertrophy, characteristic of SHR, was modified by drug treatment as evidenced by left ventricular weights as well as myocardial cell size. The cells from the subendocardium underwent selective hypertrophy in SHR which was attenuated by about 50% after atenolol treatment. Stereological analysis of electron micrographs showed that while relative mitochondrial volume was not affected by treatment, relative myofibrillar volume (%) decreased in both subepicardium (SHR = 63.28 +/- 1.25; SHR-A = 56.72 +/- 1.37) and subendocardium (SHR = 66.53 +/- 1.27; SHR-A = 58.30 +/- 1.51). This change raised the mitochondrial/myofibrillar volume ratio, which is characteristically low in SHR compared to WKY. Sarcoplasm, which included all cell constituents except mitochondria, increased with atenolol treatment, but water concentration remained unchanged. The data suggest that attenuation of hypertrophy in SHR after beta blockade is associated with selective effects on the myocardial cell involving primarily the myofibrillar cell compartment.

Attenuation of exercise conditioning by low dose beta-adrenergic receptor blockade

Because it has been shown that high doses of propranolol (40 to 80 mg orally, four times daily) markedly attenuate cardiovascular response to exercise training in healthy subjects, the effects of lower doses of this nonselective beta-adrenergic receptor antagonist on the conditioning response were investigated. Twelve normal men underwent maximal treadmill testing before and after a 6 week intensive exercise program. After an initial test, six men were randomized in a paired fashion to receive low dose propranolol and the others received no drug. The average propranolol dose +/- standard error was 22 +/- 4 mg four times daily, and the average decrease in maximal heart rate due to propranolol was 32 +/- 4 beats/min. Both groups trained at comparable intensities. At the end of the training period, propranolol was stopped and testing was repeated so that the effect of beta-receptor blockade was no longer present but the training effects still persisted. Maximal oxygen consumption increased in control subjects from 47.5 +/- 1.1 to 51.4 +/- 0.4 ml/kg per min (p less than 0.05) but was unchanged in those receiving propranolol (47.2 +/- 1.9 versus 47.4 +/- 1.5). Exercise duration increased in both groups but the increment was greater in the control group (+2.4 versus +1.1 min, p less than 0.05). It is concluded that low level beta-receptor blockade attenuates cardiovascular conditioning in normal subjects in exercise training programs. High levels of sympathetic stimulation during training appear to be important, if not essential, to the conditioning process.

Effects of beta-adrenoceptor blockade on intraocular pressure, pupil diameter, accommodation and the cardiovascular system in normal volunteers

Effects of beta-adrenoceptor blockade on intraocular pressure, pupil diameter, accommodation and the cardiovascular system in normal volunteers

Influence of beta blockade on gastric acid secretion and changes in gastric mucosal blood flow before and after parietal cell vagotomy in dogs and man.

The aim of the present study was, in paired experiments in dogs, to examine the effect of beta-receptor blockade on gastric acid secretion and mucosal blood flow before and after parietal cell vagotomy (PCV). The secretory response to pentagastrin was reduced after vagotomy. beta-Adrenergic blockade had no effect on pentagastrin-stimulated gastric acid secretion before PCV, but after PCV beta blockade caused a modest increase in acid secretion, mediated mainly by the beta 2 receptors. A similar trend was seen in man. A marked increase in mucosal blood flow occurred 30 min after propranolol and was followed by a late decrease. One may conclude that a modest beta-adrenergic tone, which reduces secretion, becomes manifest after vagal denervation and that an increase in the ratio between mucosal blood flow and acid secretion was induced by the PCV. This increase cannot be explained as a beta-receptor-mediated effect.

Effects of beta-adrenergic receptor blockade on glycogenolysis during exercise.

The purpose of this study was to determine whether beta-adrenergic receptor blockade inhibits glycogen utilization in rats during exercise. Propranolol (1 mg/kg body wt) completely blocked the glycogenolytic effect of a large dose of epinephrine given by injection but did not prevent glycogen breakdown in skeletal muscle or liver during a bout of treadmill exercise. On the contrary, exercise resulted in greater glycogen depletion in plantaris muscles of beta-blocked rats than in those of control rats, probably as a result of decreased availability of fatty acids. Increasing the availability of exogenous substrates slowed the rate of skeletal muscle glycogen depletion during exercise. However, even with increased availability of exogenous substrates, beta-blockade did not result in reduced utilization of skeletal muscle or liver glycogen. In contrast to its effect on skeletal muscle, beta-blockade markedly reduced glycogen depletion in the heart during exercise. We conclude that beta-adrenergic stimulation is of major importance in mediating glycogenolysis in the heart but is not necessary for glycogenolysis in skeletal muscle or liver during prolonged exercise.

Cardiovascular and respiratory function values in hyperthermia: The effect of beta-receptor blockade with bunitrolol

During hyperthermia in water, the rectal temperature of 12 healthy young test subjects rose by on average 1.16 degrees C. Under treatment with placebo, the pulse rate increased by 40.6 beats/min, systolic pressure by 14.6 mm Hg, oscillatory respiratory resistance fell by 0.29 hPa/1/s and time-averaged flow ventilation increased by 3.62 1/min. Under treatment with a beta-receptor blocker (10 mg of bunitrolol) there was no change in the tachycardiac response, there was slightly less of a rise of blood pressure, slightly less of a fall of oscillatory respiratory resistance and time-averaged flow ventilation remained low (2p less than 0.05). The response of the cardiovascular parameters and oscillatory respiratory resistance is discussed in connection with redistributions of blood volume during hyperthermia. The less pronounced hyperventilation is considered to be due to the effect of beta-receptor blockade in warding off external stress-induced factors.

The effect of acebutolol and propranolol on the hypoglycaemic action of glibenclamide.

1 The effect of acebutolol, a relatively selective beta-adrenoceptor blocking drug and propranolol, a non-selective one, on the hypoglycaemic action of glibenclamide after an oral glucose load has been investigated in a group of maturity-onset diabetic patients. 2 Glibenclamide significantly reduced the blood glucose levels and both acebutolol and propranolol, at therapeutic doses, were found to modify this action significantly. 3 The effect of acebutolol was slightly less than that of propranolol. The difference was not statistically significant. 4 The modes of action of sulphonylureas are reviewed and it is suggested that beta-adrenoceptor blockers may modify their effect on insulin release. This appears to be a drug interaction rather than an effect of beta-adrenoceptor blockade on glucose tolerance.

The effect of beta-adrenergic receptor blockade on intramuscular glycogen mobilization during exercise in the rat.

The effect of beta-adrenergic receptor blockade (with propranolol) on exercise-induced glycogen mobilization in rat skeletal muscles was studied. Treatment with propranolol either fully or partly prevented glycogen mobilization or had no effect at all on the process. The effects of propranolol depended on the intensity and duration of exercise and on the fiber composition of the muscle studied.

Effect of beta-adrenergic receptor blockade on development of training-induced bradycardia in rats.

Metoprolol-treated and untreated rats were subjected to the same treadmill running program for 12 weeks. After training and withdrawal of metoprolol, the treated rats had a more pronounced bradycardia during submaximal exercise than non-treated rats, although they had a lower heart weight/body weight ratio. The intrinsic heart rate (IHR) was slightly but not significantly lower in trained than in untrained untreated animals. The IHR was not altered by a period of metoprolol treatment neither alone nor in combination with training. It is concluded that chronic cardioselective beta-blockade during training augments the training-induced bradycardia but may impair the development of cardiac hypertrophy. The training-induced bradycardia is thus not related to the degree of heart rate increase during exercise for its development.