Adrenergic Receptor Blocking Drugs Research Articles

Carvedilol suppresses fatty acid oxidation and stimulates glycolysis in C2C12 cells

Beta adrenergic receptor blocking drugs (β-blockers) are used chronically in many cardiovascular diseases such as hypertension, ischemic heart disease, arrhythmia, and heart failure. Beneficial effects are associated with the inhibition of symphathetic nervous system hyperactivity, reduction of heart rate, and remodeling by blocking the mitogenic activity of catecholamines. A possible effect of β-blockers on substrate metabolism has also been suggested. The direct effects of β-blockers on mouse C2C12 cells were investigated in this study. C2C12 cells were grown in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and differentiated into myotubes in the same medium that contained 1% FBS. Palmitic acid oxidation and glycolysis were measured by using [9,10-(3)H]palmitate and [5-(3)H]glucose, respectively. The amount of (3)H(2)O was measured as an indicator of substrate usage. Carvedilol (100 µmol/L) inhibited palmitate oxidation and increased glycolysis by nearly 50%. Prazosin altered substrate metabolism in a similar fashion as carvedilol, whereas propranolol or bisoprolol were devoid of metabolic effects. When added to mimic sympathetic activation, epinephrine stimulated glycolysis but did not alter fatty acid oxidation. Based on these results, carvedilol appears to have direct effects on substrate metabolism that are related to the blockade of α1 adrenergic receptors.

Perioperative management of late metastasis of pheochromocytoma in clavicle

Perioperative management of late metastasis of pheochromocytoma in clavicle

The effect of propranolol on catecholamine clearance.

Normal subjects given propranolol increased their plasma t1/2 for infused isoproterenol from 2.68 to 6.25 minutes. Propranolol increased plasma norepinephrine (NE) levels only slightly. Propranolol increased the t1/2 of isoproterenol but not that of NE in men with autonomic nervous system degeneration. This suggests that propranolol acts on nonneuronal uptake-2 processes, rather than on uptake-1 mechanisms. alpha-Blockers slow uptake-1 and beta-blockers slow uptake-2 processes. When 27 subjects exercised, those who attained the highest plasma levels of the alpha- and beta-receptor agonist NE also had the briefest apparent t1/2 for NE. Adrenergic receptor blocking drugs slow catecholamine clearance. NE may stimulate its own clearance.

Electrophysiology of neurones of the inferior mesenteric ganglion of the cat.

Intracellular recordings were obtained from cells in vitro in the inferior mesenteric ganglia of the cat. Neurones could be classified into three types: non-spontaneous, irregular discharging and regular discharging neurones. Non-spontaneous neurones had a stable resting membrane potential and responded with action potentials to indirect preganglionic nerve stimulation and to intracellular injection of depolarizing current. Irregular discharging neurones were characterized by a discharge of excitatory post-synaptic potentials (e.p.s.p.s.) which sometimes gave rise to action potentials. This activity was abolished by hexamethonium bromide, chlorisondamine and d-tubocurarine chloride. Tetrodotoxin and a low Ca2+ -high Mg2+ solution also blocked on-going activity in irregular discharging neurones. Regular discharging neurones were characterized by a rhythmic discharge of action potentials. Each action potential was preceded by a gradual depolarization of the intracellularly recorded membrane potential. Intracellular injection of hyperpolarizing current abolished the regular discharge of action potential. No synaptic potentials were observed during hyperpolarization of the membrane potential. Nicotinic, muscarinic and adrenergic receptor blocking drugs did not modify the discharge of action potentials in regular discharging neurones. A low Ca2+ -high Mg2+ solution also had no effect on the regular discharge of action potentials. Interpolation of an action potential between spontaneous action potentials in regular discharging neurones reset the rhythm of discharge. It is suggested that regular discharging neurones were endogenously active and that these neurones provided synaptic input to irregular discharging neurones.

Calcium blocking drugs for angina pectoris.

The introduction of the calcium channel blockers for the treatment of angina pectoris has been heralded as the most significant medical event in cardiology since the introduction of the beta adrenergic receptor blocking drugs (1-5). Calcium blockers, sometimes called calcium antagonists or slow channel blockers, have as their primary mechanism of action the ability to reduce intracellular calcium ion (Ca2+) concentration in cardiac and vascular smooth muscle (6-10). In studies of isolated tissue, the drugs exert negative chronotropic, dromotropic, and inotropic effects on the heart and relax vascular smooth muscle. This latter property has generated the present intense interest in these drugs since it is now recognized that coro­ nary vasospasm may play a major role in a significant minority of patients with ischemic heart disease (11-18). In this paper we review the clinical picture of coronary vasospasm, the pharmacology of the major calcium blockers, and the use of these drugs in the treatment of Prinzmetal's or variant angina and chronic stable angina pectoris.

Mechanism of neurotensin-induced pressor effect and tachycardia in guinea pigs

Neurotensin (NT) was found to produce a dose-dependent increase of the systolic and diastolic blood pressure, and of the heart rate in anesthetized guinea pigs when injected intravenously (i.v.) as a bolus, or when infused i.v. over a 15 min period. In a small percentage (20%) of animals, bolus injections of NT evoked triphasic variations (e.g. increase followed by a decrease and a further increase) of the blood pressure associated with unpredictable changes of heart rate. The pressor effect of NT was consistently reduced by prior treatment of the animals with pentolinium, a ganglion blocking agent, a mixture of alpha and beta adrenergic receptor blocking drugs, reserpine, a drug known to deplete adrenergic neurons of their neurotransmitters, or guanethidine, a drug known to paralyse adrenergic neurons. NT-induced tachycardia was either unchanged or slightly potentiated following the administration of the latter autonomic blockers. Neither the pressor effect nor the tachycardia evoked by NT was affected by antihistaminics, antiangiotensin or by indomethacin, an inhibitor of prostaglandin synthesis. These results suggest that the pressor effect of NT in anesthetized guinea pigs is likely the result of an interaction (most likely an activation) between the peptide and the sympathetic nervous system. The increase of heart rate induced by NT appears to be due to a direct effect on the heart.

Early Mortality and Temperature Regulation in Burned Mice following Administration of Catecholamines and Adrenergic Receptor Blocking Drugs

The effect of catecholamines and adrenergic receptor blocking drugs on mortality and body temperature was studied in mice subjected to burn, tourniquet, and endotoxin shock at an environmental temperature of 25° C. Epinephrine and norepinephrine (0.5 mg/kg) injected intraperitoneally postburn increased shock mortality significantly (p < 0.05); pretreatment with these catecholamines had no effect. Pretreatment of burn- and tourniquet-traumatized mice with propranolol (25 mg/kg) significantly decreased shock mortality, while pretreatment with dibenamine (25 mg/kg) significantly lowered early mortality after endotoxin. None of the catecholamines or their blocking drugs significantly prevented the characteristic immediate fall in core temperature after the three types of shock. At 6 days postburn, however, a combination of propranolol and dibenamine caused a marked fall in core temperature (p < 0.05). These results indicate that β-catecholamine agonists could play an important role in acute burn mortality and that both α- and β-catecholamine agonists could significantly influence body temperature regulation and metabolic rate during the late postburn period.

Early Mortality and Temperature Regulation in Burned Mice following Administration of Catecholamines and Adrenergic Receptor Blocking Drugs

The effect of catecholamines and adrenergic receptor blocking drugs on mortality and body temperature was studied in mice subjected to burn, tourniquet, and endotoxin shock at an environmental temperature of 25 degrees C. Epinephrine and norepinephrine (0.5 mg/kg) injected intraperitoneally postburn increased shock mortality significantly (p less than 0.05); pretreatment with these catecholamines had no effect. Pretreatment of burn- and tourniquet-traumatized mice with propranolol (25 mg/kg) significantly decreased shock mortality, while pretreatment with dibenamine (25 mg/kg) significantly lowered early mortality after endotoxin. None of the catecholamines or their blocking drugs significantly prevented the characteristic immediate fall in core temperature after the three types of shock. At 6 days postburn, however, a combination of propranolol and dibenamine caused a marked fall in core temperature (p less than 0.05). These results indicate that beta-catecholamine agonists could play an important role in acute burn mortality and that both alpha- and beta-catecholamine agonists could significantly influence body temperature regulation and metabolic rate during the late postburn period.

Effects of systemic and intracerebral administration of adrenergic receptor blocking drugs on the conditioned avoidance behavior and maze learning in rats

(1) Effects of α- and β-adrenergic receptor blocking drugs, given systemically or intracerebrally into the brainstem, were studied on the acquisition, retention and extinction of conditioned avoidance behavior. (2) The systemic administration of β-adrenergic receptor blockers, Trasicor and GYKI 41099, led to a marked suppression of the acquisition of a two-way avoidance response but did not modify the retention or the extinction of the avoidance response. (3) Injection of GYKI 41099 into the brainstem reticular formation resulted in a decrease in the acquisition of the conditioned avoidance response. (4) The same treatment with an α-adrenergic receptor blocker, phenoxybenzamine, failed to influence the acquisition of the conditioned avoidance response. (5) These observations led to the conclusion that β-adrenergic receptors are involved in modulating the acquisition of a conditioned response although they do not play a significant role in the retention or the extinction processes.

Acute effects of adrenergic receptor blocking drugs and neuroleptic agents on pulsatile discharges of luteinizing hormone in the ovariectomized rat.

Blood samples were taken every 5 min for a 3-h period from ovariectomized (OVX) adult rats bearing chronic venous catheters. After 1 h of sampling, an experimental drug was injected through the sampling catheter. The neuroleptics, chlorpromazine and haloperidol, blocked pulsatile discharges of luteinizing hormone (LH) in some animals, for periods of 65-120 min, as did the alpha-adrenergic receptor blockers, phenoxybenzamine and phentolamine. Pimozide, a more specific dopaminergic blocking agent, had less effect, while neither the beta-adrenergic receptor blocker, propranolol, nor the control treatments had any influence on the pulsatile LH patterns. The temporal pattern of inhibition of pulsatile discharges of LH by these drugs is more rapid than the inhibition caused by estrogen treatment in the OVX rat. These results suggest the presence of alpha, but not beta, adrenergic elements in the pulsatile mode of LH release in the OVX rat. They do not support the presence of dopaminergic elements, but neither do they conclusively deny it.

Beta-adrenergic receptor blocking drugs in hyperthyroidism.

β-Adrenergic receptor blockade reduces many of the clinical manifestations of hyperthyroidism particularly tachycardia and dysrhythmias. β-Adrenergic receptor blocking drugs without intrinsic sympathomimetic activity are superior to those possessing it, probably because of the increased sensitivity to adrenergic receptor stimulation which is found in this condition. However, such treatment should not be considered as a long-term substitute for specific antithyroid therapy.

Effect of Adrenergic Blocking Agents on Sympathomimetic Amines Induced Hyperglycemia and Hyperlactacidemia

Sympathomimetic amines epinephrine and isoproterenol were administered to dogs, rabbits and pigeons, and effects on blood glucose and blood lactic acid levels were studied. Alpha and beta adrenergic receptor blocking drugs were employed to block the metabolic effects of the amines to elucidate the exact receptor status regarding the metabolic actions of sympathomimetic amines on carbohydrate metabolism. The results suggest that the receptors associated with hyperglycemic response vary depending on the species. In dogs, receptors are of beta type while in rabbits and pigeons both alpha and beta type of receptors appear to play a role. The hyperlactacidemic response, however, is associated with beta receptors in all animals studied herein.

The Clinical Pharmacology of Beta Adrenergic Receptor Blocking Drugs

Restricted accessAbstractFirst published July 1973The Clinical Pharmacology of Beta Adrenergic Receptor Blocking DrugsJ. W. PatersonVolume 18, Issue 4https://doi.org/10.1177/003693307301800414

Effect of cold on TSH secretion in man.

Short term cooling of adult human subjects fails to stimulate TSH release, whereas a prompt increase in serum TSH is observed in infants and children in response to cooling. Heat loss in infants is known to be augmented in response to cold exposure and it is possible that more effective catecholamine thermogenesis in the adult obviates the TSH response. To test this hypothesis the serum TSH response to cooling at 2 to 4° C was measured in adolescent and young adult subjects with and without administration of alpha or beta adrenergic receptor blocking drugs. Neither drug augmented the TSH response although significant hypothermia occurred. Thus, it seems that the hypothalamus of the adult has become refractory to the acute cold stimulus. Although cooling fails to evoke an acute TSH release in adults, some delayed TSH response to cooling can be observed probably in response to increased thyroxine utilization.

The influence of adrenergic receptor blocking agents on the mouse thyroid.

1. The influence of adrenergic receptor blocking drugs on the mouse thyroid gland maintained in vitro has been investigated. 2. Phentolamine, an α adrenergic blocking drug, and propranolol, a β blocking drug, inhibited the release of [131I]iodothyronines from pre-labelled mouse thyroids, which otherwise occurred when the glands were incubated in the presence of thyroid stimulating hormone, long acting thyroid stimulator, or cyclic 3′5′-adenosine monophosphate. 3. Evidence is presented to show that (a) the inhibition is not due to adrenergic blockade, (b) the effect cannot wholly be attributed to the prevention of adenyl cyclase activation, (c) the mechanism of action of the two drugs is dissimilar. 4. The observed clinical response in the treatment of thyrotoxicosis does not appear to be related to this antithyroid effect of propranolol.