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PubMed1986

The effect of peripheral catecholamine concentrations on the pituitary-adrenal response to corticotrophin releasing factor in man.

To evaluate the effect of changes in plasma catecholamines on the pituitary-adrenal response to ovine corticotrophin releasing factor (CRF) in normal man, the response to CRF alone (10 subjects) was compared responses after infusions of adrenaline (6 subjects), noradrenaline (6 subjects) and after oral administration of the alpha 2 agonist clonidine (10 subjects). Compared to control levels, plasma adrenaline and noradrenaline concentrations were increased three- and four-fold respectively by exogenous infusions, whereas plasma noradrenaline was significantly lowered by clonidine. Despite these changes in plasma catecholamine levels, the responses of plasma ACTH, cortisol and aldosterone to CRF did not differ significantly from control (CRF alone) in any of the three studies. Neither clonidine pretreatment nor catecholamine infusions altered basal levels of plasma ACTH, cortisol or aldosterone and no effect of CRF or catecholamine manipulations on plasma arginine vasopressin concentration was observed. These results show that modulation of peripheral plasma catecholamine levels within physiological limits does not affect CRF-stimulated release of ACTH or the adrenal response in normal man.

Adrenocorticotropic Hormone↗
PubMed1986

Naloxone provokes catecholamine release in phaeochromocytomas and paragangliomas.

The effects of low- (2 mg) and high-dose (10 mg) intravenous naloxone administration on circulating plasma catecholamines in four patients with proven and two patients with suspected phaeochromocytomas have been evaluated. In three out of four patients with confirmed phaeochromocytomas or paragangliomas, 10 mg naloxone resulted in a marked rise (290-575%) in circulating noradrenaline; despite combined alpha and beta-adrenoceptor blockade, in two out of four cases systolic and diastolic pressures rose whilst pulse rate fell. No response was seen to 2 mg naloxone in any patient. No humoral or pressor response was obtained in the fourth patient, who may have been secreting maximal levels of plasma noradrenaline at the time of study. In the two patients with suspected phaeochromocytoma, there was no response to naloxone: further investigations failed to reveal a source of abnormal catecholamine secretion in these patients. It is concluded that naloxone represents a new pharmacological agent which can provoke catecholamine release in patients with phaeochromocytomas; in such patients, endogenous opioids may regulate catecholamine release either from the tumour itself or from the enhanced peripheral catecholamine stores.

Adolescent↗
PubMed1995

Effects of catecholamines on regional perfusion and oxygenation in critically ill patients.

Multiple organ failure is the major cause of death in patients with sepsis. Bacterial translocation from the gut is considered to induce and maintain sepsis. Therefore, the splanchnic region plays an important role in the pathogenesis and treatment of sepsis. There is evidence for a very high risk of imbalance between oxygen delivery and oxygen consumption especially in the splanchnic region. Consequently, there is a crucial interest whether it is possible to influence the splanchnic perfusion by specific catecholamines. Unfortunately, only a few, conflicting studies have looked at the effects of the various catecholamines on regional blood flow. Therefore, a clear recommendation for a specific catecholamine regimen in septic shock is impossible. Furthermore, it is unknown whether the choice of a specific catecholamine in the treatment of septic shock affects the patient's outcome. In most patients, the use of vasopressors is indispensable because adequate haemodynamic perfusion pressure is not achieved with fluid therapy alone. The negative effects of vasopressors on splanchnic perfusion are known from studies carried out under non septic conditions. Norepinephrine and dopamine in doses of 10 micrograms/kg/min in septic animals are without negative effects on splanchnic perfusion. Preliminary results show Preliminary results show a decrease in splanchnic oxygenation in patients with septic shock treated with epinephrine. Catecholamines with beta mimetic effects are often used to increase DO2. The question as to whether dobutamine or dopamine should be used first in treatment of septic shock cannot be answered yet. Whether treatment with low dose dopamine or dopexamine actually improves renal function and splanchnic oxygenation is the purpose of ongoing studies.

Adrenergic beta-Agonists↗
PubMed1975

Metabolism of isolated kidney tubules. Independent actions of catecholamines on renal cyclic adenosine 3':5'-monophosphate levels and gluconeogenesis.

Isolated kidney cortex tubules from starved rats have been used to study the actions of catecholamines on renal adenosine 3':5' monophosphate (Ado-3':5'-P) levels and gluconeogenesis. In accordance with previous workers, norepinephrine was found to increase glucose formation from lactate and pyruvate and to a smaller degree from malate, succinate, fumarate and glutamine. The stimulatory effect of 0.5 muM norepinephrine was additive to that of 0.1 mM Ado-3':5-P, indicating an Ado-3':5'-P-independent mechanism of catecholamine action. The effects of parathyroid hormone and oleate on gluconeogenesis were also additive to that of norepinephrine. A comparative study of the actions of different catecholamine derivatives revealed that gluconeogenesis was stimulated in parallel to the alpha-adrenergic potency of the hormones, whereas Ado-3':5'-P levels were increased according to the known beta-stimulatory potency of the agents. Although isoproterenol was by far the most effective in raising Ado-3':5'-P levels, it was without effect on glucose formation from pyruvate, when added at 0.1 muM. At the same concentration, phenylephrine, which had no effect on Ado-3':5'-P levels, was the best stimulator of gluconeogenesis. The alpha-receptor blocking agent phentolamine inhibited the stimulatory effect of catecholamines on gluconeogenesis with a 50 times higher potency than propranolol, a beta-blocking agent. The fact that the stimulatory effect of Ado-3':5'-P was also blocked by propranolol, indicated an unspecific mechanism of action of this substance. The results indicate that the stimulatory effect of catecholamines on renal gluconeogenesis are mediated by an alpha-receptor and that they are independent from the stimulation of renal adenyl cyclase by these agents.

Animals↗
PubMedDate not supplied

Circulating dopamine-beta-hydroxylase (DbetaH) and catecholamines in a paediatric phaeochromocytoma.

1. Circulating catecholamines and dopamine-beta-hydroxylase (DbetaH) have been studied in a child with bilateral phaeochromocytoma. 2. Venous catheterization showed a great increase in catecholamine efflux from the left adrenal vein while DbetaH activity in the latter was only slightly elevated. 3. Circulating catecholamines fluctated greatly while DbetaH activity decreased gradually during the removal of the tumours. 4. Post-operatively, circulating catecholamines declined to normal values while DbetaH activity returned to pre-operative levels. 5. It is concluded that these tumours released circulating catecholamines independent of an exocytotic secretion of DbetaH and that the circulating DbetaH reflected the activity of the sympathetic nervous system.

Adrenal Gland Neoplasms↗
PubMed1989

Evidence that increases in circulating catecholamines of adrenal origin are not involved in pressor response to bilateral carotid occlusion in anaesthetized dogs.

1. We studied whether or not circulating catecholamines of adrenal origin play a major role in cardiovascular responses evoked by bilateral carotid artery occlusion (3 min) in anaesthetized dogs. 2. In the control group, the following parameters increased significantly (P less than 0.05) during bilateral carotid occlusion: aortic systolic pressure, heart rate, net adrenal catecholamine output, net renal noradrenaline output, and plasma catecholamine concentrations in aortic blood. Similar responses were obtained during the second occlusion performed approximately 25 min after the first occlusion. 3. After functional adrenalectomy (ADRX: diversion of adrenal venous blood flow), the increase in aortic adrenaline concentration observed during bilateral carotid occlusion was abolished. The increase in aortic noradrenaline concentration during the occlusion was significantly attenuated by approximately 60% (P less than 0.01) after ADRX. 4. The increase in net renal noradrenaline output during bilateral carotid occlusion after ADRX was not different from that observed before ADRX. Similarly, the response of aortic systolic pressure and heart rate during the occlusion was unaffected by ADRX. Furthermore, the increase in net adrenal catecholamine output during the occlusion was not affected by ADRX itself. 5. From these results, we conclude that the increase in circulating catecholamines of adrenal origin during bilateral carotid occlusion is not a major determinant for the increases in aortic pressure and heart rate. The results suggest that these cardiovascular responses during the occlusion are mediated principally by neuronal noradrenaline released from peripheral sympathetic nerve terminals.

Adrenal Glands↗
PubMed1999

Role of calcium channels in catecholamine secretion in the rat adrenal gland.

1. We elucidated the contribution of voltage-dependent Ca2+ channels to cholinergic control of catecholamine secretion in the isolated perfused rat adrenal gland. 2. Nifedipine (0.3-3 microM) inhibited increases in noradrenaline output induced by transmural electrical stimulation (1-10 Hz) and acetylcholine (6-200 microM), whereas it only slightly inhibited the adrenaline output responses. Nifedipine also inhibited the catecholamine output response induced by 1, 1-dimethyl-4-phenyl-piperazinium (DMPP; 5-40 microM) but not by methacholine (10-300 microM). 3. omega-Conotoxin MVIIC (10-1000 nM) inhibited the catecholamine output responses induced by electrical stimulation but not by acetylcholine, DMPP and methacholine. 4. omega-Conotoxin GVIA (50-500 nM) had no inhibitory effect on the catecholamine output responses. 5. These results suggest that L-type Ca2+ channels are responsible for adrenal catecholamine secretion mediated by nicotinic receptors but not by muscarinic receptors, and that their contribution to noradrenaline secretion may be greater than that to adrenaline secretion. P/Q-type Ca2+ channels may control the secretion at a presynaptic site.

Acetylcholine↗
PubMed1982

Calcium uptake and catecholamine secretion by cultured bovine adrenal medulla cells.

The uptake of 45Ca2+ and secretion of catecholamines by primary cultures of adrenal medulla cells were studied. Nicotine, veratridine, potassium, and Ionomycin stimulate both the accumulation of 45Ca2+ and the secretion of catecholamines. Nicotinic antagonists block 45Ca2+ uptake induced by nicotine, tetrodotoxin blocks 45Ca2+ uptake induced by veratridine, and D600 or secretion induced by Ionomycin. The EC50 for nicotine is 3 microM for catecholamine secretion and 10 microM for 45Ca2+ uptake, while the EC50s for veratridine-stimulated uptake and secretion are approximately the same (75 microM). Kinetic studies show that the uptake of Ca2+ is rapid and appears to precede the secretion of catecholamines, and that the rate of uptake declines rapidly. The 50 mM-K+ show saturation kinetics with respect to external calcium concentrations at about 2 mM. On the other hand, the uptake of 45Ca2+ stimulated by nicotine does not become saturated at external calcium concentrations of 10 mM although the secretion of catecholamines reaches a maximum at external calcium concentrations of 2 mM. The data suggest that depolarizing agents such as veratridine and 50 mM-K+ stimulate 45Ca2+ entry through voltage-sensitive calcium channels, while nicotinic agonists stimulate calcium entry through the acetylcholine receptor ion channels as well as through voltage-sensitive calcium channels.

Adrenal Medulla↗
PubMed1984

Parallel but separate release of catecholamines and acetylcholinesterase from stimulated adrenal chromaffin cells in culture.

A pharmacological study was made of the effects of veratridine and lasalocid on the release of catecholamines, acetylcholinesterase (AChE) and dopamine-beta-hydroxylase (DBH) from cultures of isolated bovine adrenal chromaffin cells. Exposure of the cultures to veratridine resulted in concomitant release of catecholamines and AChE into the external medium in a dose-dependent and Ca2+-dependent manner. A Ca2+ ionophore, lasalocid, also produced a dose-dependent and parallel release of both catecholamines and AChE. The release of the two components was accompanied by release of DBH. The present results provide pharmacological evidence for a parallel release of catecholamines, AChE, and DBH from cultured adrenal chromaffin cells, and the stoichiometry of the release evoked by different secretagogues suggests that AChE and catecholamines are released from different cellular compartments.

Acetylcholinesterase↗
PubMed1985

Arachidonic acid release and catecholamine secretion from digitonin-treated chromaffin cells: effects of micromolar calcium, phorbol ester, and protein alkylating agents.

The relationship between catecholamine secretion and arachidonic acid release from digitonin-treated chromaffin cells was investigated. Digitonin renders permeable the plasma membranes of bovine adrenal chromaffin cells to Ca2+, ATP, and proteins. Digitonin-treated cells undergo exocytosis of catecholamine in response to micromolar Ca2+ in the medium. The addition of micromolar Ca2+ to digitonin-treated chromaffin cells that had been prelabeled with [3H]arachidonic acid caused a marked increase in the release of [3H]arachidonic acid. The time course of [3H]arachidonic acid release paralleled catecholamine secretion. Although [3H]arachidonic acid release and exocytosis were both activated by free Ca2+ in the micromolar range, the activation of [3H]arachidonic acid release occurred at Ca2+ concentrations slightly lower than those required to activate exocytosis. Pretreatment of the chromaffin cells with N-ethylmaleimide (NEM) or p-bromophenacyl bromide (BPB) resulted in dose-dependent inhibition of 10 microM Ca2+-stimulated [3H]arachidonic acid release and exocytosis. The IC50 of NEM for both [3H]arachidonic acid release and exocytosis was 40 microM. The IC50 of BPB for both events was 25 microM. High concentrations (5-20 mM) of Mg2+ caused inhibition of catecholamine secretion without altering [3H]arachidonic acid release. A phorbol ester that activates protein kinase C, 12-O-tetradecanoylphorbol-13-acetate (TPA), caused enhancement of both [3H]arachidonic acid release and exocytosis. The findings demonstrate that [3H]arachidonic acid release is stimulated during catecholamine secretion from digitonin-treated chromaffin cells and they are consistent with a role for phospholipase A2 in exocytosis from chromaffin cells. Furthermore the data suggest that protein kinase C can modulate both arachidonic acid release and exocytosis.

Acetophenones↗
PubMed1986

Characterization of a dopaminergic receptor that modulates adrenomedullary catecholamine release.

Nicotine evokes the release of catecholamines from bovine adrenal glands perfused with oxygenated Krebs-bicarbonate solution. Two 2-min pulses of 5 microM nicotine, at 40-min intervals (S1 and S2), gave net catecholamine outputs of 45.2 +/- 3.6 and 29.1 +/- 3.5 micrograms/8 min, respectively. Apomorphine (1 or 10 microM) markedly inhibited catecholamine release during S2 to 9.1 +/- 2.2 and 0.5 micrograms/8 min, respectively. Haloperidol (0.5 microM) reversed the inhibitory effects of apomorphine. Haloperidol alone enhanced catecholamine release induced by nicotine to 67.9 +/- 7.9 micrograms/8 min. [3H]Spiperone binds to adrenomedullary membranes with a KD of 0.24 nM and a Bmax of 117 fmol/mg of protein. Whereas spiperone and haloperidol potently displaced such binding, 3,4-dihydroxyphenylethylamine (dopamine) and sulpiride were poorer displacers, and SCH23390, prazosin, phenoxybenzamine, propranolol, BAY-K-8644, and nitrendipine did not displace [3H]spiperone bound. These data strongly suggest that, as in the cat, the bovine adrenal medulla chromaffin cell contains a dopaminergic receptor that modulates the catecholamine secretory process triggered by stimulation of the nicotinic cholinoceptor. Such a receptor seems to be of the D2 type and might be involved in a sympatho-adrenal cooperative mechanism contributing to the maintenance of cardiovascular homeostasis during stressful situations as well as to the pathogenesis of hypertension. If so, selective dopaminergic agonists might prove clinically useful in the treatment of hypertension.

Adrenal Medulla↗
PubMed1987

Intracellular pH and catecholamine synthesis in cultured bovine adrenal medullary cells: effect of extracellular Na+ removal.

Incubation of cultured bovine adrenal medullary cells in Na+-free sucrose medium or in Na+-free Cs+ medium enhanced the synthesis of 14C-catecholamines from [14C]tyrosine about two- to threefold or sixfold, respectively. The increment of 14C-catecholamine synthesis produced by Na+-free medium was partially dependent on the presence of Ca2+ in the medium. Dibutyryl cyclic AMP also stimulated the synthesis of 14C-catecholamines in adrenal medullary cells, and the effects of Na+ removal and dibutyryl cyclic AMP (5 mM) on the synthesis were almost additive. The intracellular pH measured by using a weak acid 5,5-dimethyloxazolidine-2,4-dione was 7.14 in control cells and when Na+ was replaced by sucrose or Cs+, it shifted down to 6.56 or 5.66, respectively. The fall in intracellular pH and the stimulation of 14C-catecholamine synthesis were similarly dependent on the concentration of Na+ in the medium. The optimal pH of soluble tyrosine hydroxylase was 5.5-6.0 both in control cells and in cells incubated in Na+-free medium. These results suggest that removal of extracellular Na+ increases the synthesis of catecholamines, at least in part, by shifting the intracellular pH toward the optimal pH of tyrosine hydroxylase.

Adrenal Medulla↗
PubMed1989

Direct adrenal medullary catecholamine response to hypoxia in fetal sheep.

The present study was designed to investigate the direct response of fetal adrenomedullary cells to hypoxia, and the possible change in this responsiveness with maturation. Ovine fetal adrenomedullary cells, when exposed to 30 min of hypoxia induced by perfusing with Krebs-Henseleit solution equilibrated with 1% O2, released significantly greater amounts of total catecholamine into the perfusate, compared to basal conditions. After a 1-h control period, a second 30-min hypoxic episode stimulated a catecholamine response which was significantly smaller in magnitude than the first. Following the two hypoxic episodes, the cells were capable of responding to 50 mM KCl with a large increase in total catecholamine release. During the first hypoxic episode, the release of both norepinephrine and epinephrine was stimulated by equal magnitude. Fetal adrenomedullary cells obtained from fetuses at 100, 120, and 130 days gestation showed similar responsiveness to the same hypoxic stimulus, and these responses were not different from that observed in maternal adrenomedullary cells. On the contrary, responsiveness to KCl-induced depolarization was greatest in cells obtained from fetuses at 130 days gestation when compared to that in the younger fetuses. This increased responsiveness to KCl was accompanied by a greater catecholamine store in the adrenal medulla of the fetuses at this gestational age. These results suggest that ovine fetal adrenomedullary cells can respond directly to hypoxia by releasing catecholamines. This direct responsiveness became desensitized after repeated exposure. Finally, a decrease in direct responsiveness to hypoxia associated with maturation could be demonstrated.

Adrenal Medulla↗
PubMed1989

Carbachol-induced cosecretion of immunoreactive atrial natriuretic peptides with catecholamines from cultured bovine adrenal medullary cells.

The distribution and secretion of atrial natriuretic peptides (ANPs) were investigated in bovine adrenal medulla. (1) Cultured bovine adrenal medullary cells (2 x 10(6)/dish) contained 100.4 +/- 6.0 fmol of immunoreactive ANP (IR-ANP) and 207.3 +/- 6.6 nmol of catecholamines as epinephrine plus norepinephrine. (2) Stimulation of nicotinic but not muscarinic acetylcholine receptors caused a cosecretion of IR-ANP and catecholamines corresponding to the ratio of IR-ANP to catecholamines in cultured bovine adrenal medullary cells. (3) Carbachol-stimulated secretion of IR-ANP was dependent on the presence of extracellular Ca2+. (4) Chromaffin granules isolated from bovine adrenal medulla contained large amounts of IR-ANP and catecholamines, in the same ratio as did cultured adrenal medullary cells. (5) Reverse-phase HPLC analysis showed that both stored and secreted IR-ANP consisted of two components, which eluted at the position of ANP(99-126) or ANP(1-126). These results indicate that ANPs are stored as ANP(99-126) and ANP(1-126) in chromaffin granules, and are cosecreted in parallel with catecholamines in a Ca2+-dependent manner by the stimulation of nicotinic acetylcholine receptors.

Adrenal Medulla↗
PubMed1990

Effects of hypoxia on the catecholamine release, Ca2+ uptake, and cytosolic free Ca2+ concentration in cultured bovine adrenal chromaffin cells.

The purpose of the present study is to clarify the effects of hypoxia on catecholamine release and its mechanism of action. For this purpose, using cultured bovine adrenal chromaffin cells, we examined the effects of hypoxia on high (55 mM) K(+)-induced increases in catecholamine release, in cytosolic free Ca2+ concentration ([Ca2+]i), and in 45Ca2+ uptake. Experiments were carried out in media preequilibrated with a gas mixture of either 21% O2/79% N2 (control) or 100% N2 (hypoxia). High K(+)-induced catecholamine release was inhibited by hypoxia to approximately 40% of the control value, but on reoxygenation the release returned to control levels. Hypoxia had little effect on ATP concentrations in the cells. In the hypoxic medium, [Ca2+]i (measured using fura-2) gradually increased and reached a plateau of approximately 1.0 microM at 30 min, whereas the level was constant in the control medium (approximately 200 nM). High K(+)-induced increases in [Ca2+]i were inhibited by hypoxia to approximately 30% of the control value. In the cells permeabilized by digitonin, catecholamine release induced by Ca2+ was unaffected by hypoxia. Hypoxia had little effect on basal 45Ca2+ uptake into the cells, but high K(+)-induced 45Ca2+ uptake was inhibited by hypoxia. These results suggest that hypoxia inhibits high K(+)-induced catecholamine release and that this inhibition is mainly the result of the inhibition of high K(+)-induced increases in [Ca2+]i subsequent to the inhibition of Ca2+ influx through voltage-dependent Ca2+ channels.

Adenosine Triphosphate↗
PubMed1996

Effects of catecholamines on isolated human colonic smooth muscle.

1. The effects of catecholamines and some adrenoceptor agonists and antagonists on isolated preparations of human colonic smooth muscle obtained from surgical resections were examined. 2. Strips of circular smooth muscle displayed rhythmic myogenic spontaneous contractions which were inhibited by catecholamines with an order of potency of isoprenaline (1.0) > noradrenaline (0.32) > adrenaline (0.2). Phentolamine (0.7 microM) significantly shifted the noradrenaline concentration-response curve (CRC) to the right but had no significant effect on isoprenaline or adrenaline. Propranolol (1 microM) significantly shifted the isoprenaline to the right but had no significant effect on noradrenaline or adrenaline. 3. Salbutamol (30 microM) had no inhibitory effect on the spontaneous activity and ICI 118,551 (1 microM) had no effect on inhibitory responses to isoprenaline. Betaxolol (1 microM) significantly shifted the CRC to isoprenaline to the right. BRL 37344 had no effect on spontaneous activity. 4. Responsiveness of circular strips to catecholamines was not affected by age of the patient and no consistent differences between males and females were shown. 5. Strips of taenia coli exhibited little or no spontaneous phasic activity. Noradrenaline and isoprenaline relaxed KCl-induced tone. The effects of noradrenaline and isoprenaline were antagonized by propranolol but not by phentolamine. BRL 37344 had no effect on KCl-induced tone. 6. In conclusion, catecholamines relaxed spontaneous activity of human colon circular smooth muscle through an action on both alpha- and beta-adrenoceptors. The alpha-adrenoceptors were of the alpha 1-subtype. The beta-adrenoceptor-mediated relaxation appeared to be primarily beta 1. In taenia coli, catecholamines relaxed KCl-induced tone via beta-adrenoceptors only.

Adrenergic alpha-Agonists↗
PubMed1976

The different effects of D-600 (methoxyverapamil) on the release of adrenal catecholamines induced by acetylcholine, high potassium or sodium deprivation.

1 Bovine adrenal glands were perfused with Locke solution and catecholamine release was induced by acetylcholine, by a depolarizing concentration of potassium, or by omission of sodium from the perfusion fluid. 2 D-600 (methoxyverapamil) at the concentration of 30 muM produced a 23% inhibition of catecholamine release evoked by acetylcholine (0.1 mM) in the presence of physostigmine (10 muM). 3 A concentration of D-600 of 0.3 mM produced 86% and 85% inhibition in the output of catecholamines in response to acetylcholine and high potassium respectively. 4 D-600 (0.3 mM) failed to block the release of catecholamines evoked by sodium deprivation. 5 The results suggest the involvement of intracellular calcium in the exocytotic release of catecholamines induced by sodium omission.

Acetylcholine↗
PubMed1986

The role of catecholamines in the production of ischaemia-induced ventricular arrhythmias in the rat in vivo and in vitro.

The role of catecholamines in the production of ischaemia-induced ventricular arrhythmias in vivo and in vitro was studied using coronary artery ligation in the rat. Increases in plasma catecholamine concentrations during coronary artery ligation in pentobarbitone-anaesthetized animals were prevented by either acute adrenalectomy or chronic adrenal demedullation, but these procedures did not protect against the occurrence of ventricular arrhythmias. Thus plasma catecholamines were not obligatory mediators of arrhythmogenesis. Three protocols were used in vitro to evaluate the possible influence of intramyocardial release of noradrenaline, produced by the local conditions of ischaemia, on the production of ventricular arrhythmias. During coronary artery ligation in isolated perfused hearts, no enhanced output of 3H could be detected from [3H]-noradrenaline loaded hearts, even in the presence of inhibitors of catecholamine uptake processes, although washout of lactate from ischaemic regions was readily demonstrable. Both optical isomers of propranolol were equally effective in reducing the incidence of arrhythmias, implying a non-specific effect, since the (+)-isomer possesses considerably less beta-adrenoceptor blocking activity. The equipotency of optical isomers of propranolol combined with a lack of effect of atenolol suggested that arrhythmia production was not a consequence of beta-adrenoceptor stimulation. The alpha-adrenoceptor blockers phentolamine and prazosin, both exerted antiarrhythmic actions of similar potency, but phenoxybenzamine and trimazosin had no significant effects. An evaluation of the pharmacological properties of the alpha-adrenoceptor blockers showed that those drugs which had demonstrable local anaesthetic properties also exerted significant antiarrhythmic effects. No relationship was found between potency of alpha-adrenoceptor blockade and antiarrhythmic efficacy. The overall conclusion from these multifaceted approaches was that catecholamines were not necessary mediators of the early phase of ventricular arrhythmias in the rat.

Adrenal Medulla↗