Role Of Adrenergic Mechanisms Research Articles

Sequential changes in plasma renin activity and plasma catecholamines in mildly hypertensive patients during acute, furosemide-induced body-fluid loss.

To evaluate the role of adrenergic mechanisms in the acute response of renin to furosemide, plasma renin activity (PRA) and plasma catecholamine concentrations were measured for 3 h after i.v. administration of furosemide 1 mg/kg to 8 patients with mild essential hypertension. Furosemide induced a prompt and long-lasting increase in renin, with PRA more than doubled at all times. The increase in PRA within the first 30 min paralleled the peak increases in urinary water and sodium flow rates, and significant decreases in plasma volume and central venous pressure. There was no change in plasma catecholamine concentrations. Plasma noradrenaline was increased significantly at 60 min and adrenaline at 90 min, once furosemide had induced a marked loss of body-fluid and approximately 65% decrease in central venous pressure. Both catecholamines remained elevated until the end of the study, whereas urinary water and sodium flow rates had returned to their pre-treatment values by 150 min. Mean blood pressure was essentially unchanged throughout the study, whereas heart rate increased significantly after 90 min. The findings suggest that in mildly hypertensive patients adrenergic mechanisms are not involved in the initial renin response to furosemide, but they come into play later, probably as a result of reflex sympathetic activation triggered by marked volume depletion.

Role of adrenergic mechanisms in the development of cerebrovascular disturbances in acute myocardial ischemia

Acute experiments were made on cats to study the general and local cerebral blood flow, the cerebrovascular tone and systemic hemodynamics during acute myocardial ischemia. Occlusion of the coronary artery resulted in the reduction of the blood flow in the carotid artery and brain cortex, decreased arterial pressure, and the cardiac output. Short-term vasodilatation was replaced by prolonged vasoconstriction which increased during myocardial ischemia. The blockade of beta-adrenoreceptors with propranolol reduced vasoconstriction. The blockade of alpha-adrenoreceptors removed or distorted vasoconstriction of the brain and hind limb vessels. The mechanisms by which brain circulatory disorders occur are discussed.

The role of adrenergic mechanisms in thermoregulatory control of blood flow through capillaries and arteriovenous anastomoses in the sheep hind limb.

The possible role of adrenergic mechanisms in thermoregulatory changes in the partition of femoral blood flow between nutrient (capillary) and non-nutrient (arteriovenous anastomoses, AVA) circuits in the hind limb of conscious sheep has been investigated employing radioactive microsphere and electromagnetic blood flow measurement techniques. Constriction of AVAs, normally induced by spinal cooling, could be inhibited by phentolamine, whereas dilatation of AVAs, normally induced by spinal heating, could be inhibited by noradrenaline or methoxamine. AVA constriction could be induced by noradrenaline or methoxamine, or dilatation by phentolamine. Isoprenaline had a small dilator and propranolol a small constrictor effect on AVAs. It is concluded that adrenergic pathways involving predominantly alpha-receptors play a role in thermoregulatory changes in skin blood flow (through AVAs) elicited by manipulation of CNS temperature; under these conditions, beta-receptors do not play any role, although manipulation of their activity will influence AVAs under non-thermoregulatory conditions. Capillary blood flows in skin, bone and fat were sensitive, at different ambient temperatures and to varying degrees, to some alpha- and beta-adrenergic agents.

The role of adrenergic mechanisms in the blood pressure regulation of leg-amputees.

An increased occurrence of hypertension has been reported among leg-amputees. In order to investigate whether leg amputation is followed by an elevation of sympathetic tone, possibly enhanced by continuous mechanical irritation of the amputation stump by wearing a prosthesis, blood pressure (BP), pulse-rate (PR) and plasma catecholamines (norepinephrine, NE, and epinephrine, E) were measured in six hypertensive leg-amputees during prosthesis walking as well as during irritation of the amputation stump by vacuum suction in the supine position. Six patients suffering from essential hypertension and six normotensive subjects served as control groups. Basal levels of plasma NE and E did not differ in the three investigated groups. Mechanical stump(limb) irritation as well as walking induced a rise of NE but not of E, accompanied by a rise of BP and PR in amputees as well as in the control subjects. Elevation of NE and BP was most accentuated in hypertensive amputees when walking with prosthesis. Within each investigated group there was a positive correlation between NE and mean arterial blood pressure (MAP), (p less than 0.001 in hypertensive amputees and non-amputees, p less than 0.05 in normotensives). We conclude that mechanical limb irritation induces a rise of BP by sympathetic nervous stimulation. Thus wearing of a vacuum-prosthesis may support a consistent rise in BP.

Adrenergic regulation of glucagon and insulin secretion during immobilization stress in normal and spontaneously diabetic BB rats.

To test for a possible role of adrenergic mechanisms in the altered glucagon secretion in the spontaneously diabetic "BB" rat, the responses of glucose, insulin, and glucagon to adrenergic blocking agents in diabetic and normal rats were compared at rest and during 2 h of immobilization stress. In unstressed normal rats, phentolamine alone caused a 20 mg/dl fall in glycemia, 1.2 ng/ml rise in insulin (IRI), and no change in glucagon (IRG), whereas the only effect of propranolol was a minor rise in glycemia. Stress caused increments in glycemia of 72 mg/dl and in IRG of 94 pg/ml, and no change in IRI. Phentolamine significantly attenuated the stress-related increments, and IRI increased by the same amount as in the unstressed state. Propranolol exhibited no statistically significant effects on the response to stress. These findings are consistent with alpha-adrenergic stimulation of IRG and suppression of IRI secretion. In unstressed diabetic rats (mean time 0 glycemia, 431 mg/dl), propranolol caused only a small rise in glycemia, whereas phentolamine induced marked increments of glycemia (131 mg/dl) and IRG (116 pg/ml). Stress alone did likewise (189 mg/dl, 122 pg/ml) as did stress with the phentolamine (271 mg/dl, 144 pg/ml). However propranolol significantly attenuated the stress-induced increments in glycemia (88 mg/dl) and IRG (82 pg/ml). Thus both alpha- and beta-adrenergic receptors influence IRG secretion in the diabetic rats. An in vivo model for elucidating neural control of glucoregulation has been developed that is independent of cardiovascular fitness.

What - if any - is the role of adrenergic mechanisms in histamine release from mast cells?

The effects of catecholamines on histamine release from rat peritoneal mast cells, was studied in an in vitro system. It was found that norepinephrine (10(-5)-101(-3) M) exerts a significant, dose related, repressive effect on compound 48/80-induced histamine release. This effect is greatly potentiated by beta-antagonists and is noticeable throughout the concentration range 10(-11)-10(-3) M norepinephrine. Phentolamine diminishes the repressive effect that norepinephrine shows at 10(-5) M. Norepinephrine (10(-5) M) totally inhibits the progressive histamine release induced by both compound 48/80 and strontium (10 muM) in non-Ca2+-depleted cells. The release that is dependent on extracellular calcium is inhibited by norepinephrine. The repressive effect of norepinephrine at 10(-3) is counteracted by 5.6 mM D-glucose, 2-deoxyglucose abolishes this effect. The repression of histamine release by 10(-5) M norepinephrine is not influenced by D-glucose. These results suggest that the effects on histamine release, observed within a low concentration range of norepinephrine (less than 10(-3) M), may be due to alpha-adrenoreceptor mechanisms and an interference in transmembrane calcium transport. Our data further suggest that norepinephrine at 10(-3) M may inhibit oxidative phosphorylation. Isoproterenol and epinephrine (10(-9)-10(-5) M) show little effect on 48/80-induced histamine release in a normal medium. However, when calcium is excluded from the medium, histamine release is potentiated. These results seem to indicate that isoproterenol and epinephrine act by displacing intracellular calcium, making it available for the exocytosis process.

Epinephrine and norepinephrine are cleared through beta-adrenergic, but not alpha-adrenergic, mechanisms in man

Although catecholamines are rapidly removed from the extracellular fluid, the role of adrenergic mechanisms in the clearance of epinephrine and norepinephrine has not been defined. In five normal human subjects, mean (± SE) plasma epinephrine concentrations did not change during control infusions, rose from 21 ± 6 pg/ml to 834 ± 84 pg/ml during the infusion of epinephrine (50 ng/kg/min) over 180 min and to 853 ± 112 pg/ml during the infusion of epinephrine plus phentolamine (500 μg/min after a 5.0 mg loading dose infused over 2 min), but to 2400 ± 104 pg/ml during the infusion of epinephrine plus propranolol (80 μg/min after a 5.0 mg loading dose infused over 2 min), indicating that β-adrenergic blockade sharply reduces the clearance of epinephrine in man. In separate studies in seven subjects, similar increments in plasma epinephrine occurred during the infusion of epinephrine alone and the clearance of epinephrine was comparably reduced during the infusion of epinephrine plus propranolol and during the infusion of epinephrine plus propranolol plus phentolamine, suggesting that the reduction of epinephrine clearance produced by β-adrenergic blockade during epinephrine infusion is not mediated by an α-adrenergic reduction of blood flow to organs of epinephrine clearance. Endogenous plasma norepinephrine concentrations doubled during the infusion of phentolamine without propranolol but rose to nearly fourfold higher values during the infusion of phentolamine with propranolol indicating that β-adrenergic blockade reduces the clearance of norepinephrine as well as that of epinephrine. These findings indicate that epinephrine and norepinephrine are cleared through β-adrenergic, but not α-adrenergic, mechanisms in man.

Activation of brain catecholaminergic neurons by cardiac vagal afferents during acute myocardial ischemia in the rat.

Activation of brain catecholaminergic neurons by cardiac vagal afferents during acute myocardial ischemia in the rat.

Increased pulmonary alpha-adrenergic and reduced beta-adrenergic receptors in experimental asthma.

The role of adrenergic mechanisms in the pathogenesis of asthma is controversial. Increased airways resistance in asthmatics is reversed by β-adrenergic receptor agonists such as isoprenaline, and it has been suggested that β-adrenergic activity is diminished in this condition1. This is supported by studies showing reduced metabolic responses to β-adrenergic agonists2,3 and fewer lymphocyte β-adrenergic receptors in asthmatics than in normal subjects4. However, the main contributory factor to diminished β-receptor responsiveness is probably a history of treatment with β-adrenergic agonists, resulting in tachyphylaxis5,6. Nevertheless, similar but less pronounced changes have been observed in untreated asthmatic patients7, α-Adrenergic agonists produce bronchoconstriction in asthmatic patients, but not in normal subjects8,9. Similarly, in vitro studies show α-adrenergic receptor-mediated constriction of bronchial smooth muscle from patients with increased airways resistance, but not from normal controls10,11. In addition increased α-adrenergic receptor-mediated responses in vascular and pupillary smooth muscle have been reported in asthmatics12. Using radioligand binding techniques, we have investigated the possibility that changes in numbers of α- and β-adrenergic receptors or their affinity are associated with the changes in adrenergic responsiveness observed in asthma. We report here that increased α- and fewer β-adrenergic receptors were observed in pulmonary homogenates of an animal model of chronic asthma than in those from controls.

Role of adrenergic mechanism in ketogenesis.

Ketogenesis is a kind of physiological and biochemical imbalance between glycogenolysis, gluconeogenesis and lipolysis, which are delicately regulated by several hormones. The purpose of these experiments in rats is whether the administration of epinephrine, which has potent actions on glycogenolysis and lipolysis, can make the similar ketogenic state as glucagon or anti-insulin serum and how α- or β-adrenergic blockade acts against the rapid effect of epinephrine. As a result, the three hour infusion of epinephrine raised up plasma glucose rapidly and plasma ketones gradually and increased the ketogenic capacity of liver. On this time liver glycogen was exhausted almost completely and liver carnitine was elevated to the same level of fasted rats. The additional administration of α-adrenergic blockade blunted the effect of epinephrine on plasma glucose, plasma ketones and ketogenic capacity of the liver. On the other hand, the additional administration of β-adrenergic blockade aggravated plasma glucose furthermore and had less effect against epinephrine on plasma ketones and ketogenic capacity of the liver. The elevated liver carnitine with epinephrine was not affected by either α- or β-adrenergic blockade. From these findings, we concluded that the rapid ketogenic effect of epinephrine is mainly mediated by a-adrenergic effect of it.

Role of adrenergic mechanisms in cardiac and respiratory effects of digoxin.

The respiratory and cardiac effects of digoxin the the dog were both markedly reduced by ganglionic blockade and reserpinization, but only the cardiac effects were significantly modified by propranolol. This gives support to our previous hypothesis that digoxin cardiac effects depend, in part, on extra-cardiac mechanisms and its relationship with respiratory effects results from the fact that both effects are dependent directly and reflexly from sympathetic nervous activation.

The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man.

Sequential determinations of glucose outflow and inflow, and rates of gluconeogenesis from alanine, before, during and after insulin-induced hypoglycemia were obtained in relation to alterations in circulating epinephrine, norepinephrine, glucagon, cortisol, and growth hormone in six normal subjects. Insulin decreased the mean (+/-SEM) plasma glucose from 89+/-3 to 39+/-2 mg/dl 25 min after injection, but this decline ceased despite serum insulin levels of 153+/-22 mul/ml. Before insulin, glucose inflow and outflow were constant averaging 125.3+/-7.1 mg/kg per h. 15 min after insulin, mean glucose outflow increased threefold, but then decreased at 25 min, reaching a rate 15% less than the preinsulin rate. Glucose inflow decreased 80% 15 min after insulin, but increased at 25 min, reaching a maximum of twice the basal rate. Gluconeogenesis from alanine decreased 68% 15 min after insulin, but returned to preinsulin rates at 25 min, and remained constant for the next 25 min, after which it increased linearly. A fourfold increase in mean plasma epinephrine was found 20 min after insulin, with maximal levels 50 times basal. Plasma norepinephrine concentrations first increased significantly at 25 min after insulin, whereas significantly increased levels of cortisol and glucagon occurred at 30 min, and growth hormone at 40 min after insulin. Thus, insulin-induced hypoglycemia in man results from both a decrease in glucose production and an increase in glucose utilization. Accelerated glycogenolysis produced much of the initial, posthypoglycemic increment in glucose production. The contribution of glycogenolysis decreased with time, while that of gluconeogenesis from alanine increased. Of the hormones studied, only the increments in plasma catecholamines preceded or coincided with the measured increase in glucose production after hypoglycemia. It therefore seems probable that adrenergic mechanisms play a major role in the initiation of counter-regulatory responses to insulin-induced hypoglycemia in man.

Role of adrenergic mechanisms in the development of cardiac hypertrophy.

This experiment was designed to study the role of cardiac beta-adrenergic mechanisms in the development of hypertrophy in rats. The suprarenal abdominal aorta was banded, resulting in an increase in cardiac wt-body wt ratio. A group of rats received a sham operation. Half of the banded rats were treated with practolol, 2.0 mg/kg intraperitoneally every 12 hr for the 6 days after banding. The effectiveness of cardiac beta-adrenergic blockade was confirmed by absence of an increase in heart rate following intravenous isoproterenol at various times between practolol injections. Practolol did not affect the gradient in the banded groups. Six animals in each banded group were sacrificed daily for 6 days. The right and left ventricles were dissected separately and weighed. RV-body weight ratios increased similarly in both banded groups. LV-body weight ratio (g/kg) was 2.17 +/- 0.043 in sham rats, and it attained maximal levels of 3.03 +/- 0.10 within 6 days in banded untreated rats and 2.96 +/- 0.14 in banded rats receiving practolol. Therefore, beta-adrenergic mechanisms were not involved in the development of hypertrophy due to increased afterload. Also, these findings are not consistent with the Meerson hypothesis, since hypertrophy occurred despite the reduction in myocardial O2 consumption due to practolol.

Renal intracortical blood flow during hemorrhage: role of adrenergic mechanisms.

Hemorrhagic hypotensin in anesthetized dogs produced a redistribution of renal blood flow from the outer to the inner cortex. The role of adrenergic mechanisms in this redistribution was studied in anesthetized dogs using a radioactive microspheres to determine intrarenal blood flow. Neither renal denervation, nor pretreatment with reserpine altered the characteristic redistribution of renal cortical flow during hemorrhage. These observations suggest that neither intact renal nerves nor circulating catecholamines are necessary for the redistribution of renal intracortical blood flow during hemorrhagic hypotension, and the role of myogenic autoregulation is emphasized.

Possible role of adrenergic mechanisms in the systemic anti-inflammatory activity of acetic acid in rats

An attempt was made to determine whether or not the systemic anti-inflammatory activity of acetic acid, exerted upon either carrageenin or yeast-induced paw oedema in rats, was mediated via adrenergic mechanisms. It was found that the anti-inflammatory activity of acetic acid was unaffected by both α- and β-adrenoceptor antagonists, prior depletion of catecholamine stores, acute denervation of the hind paw, and by adrenergic neurone blockade. The reduction, by guanethidine, of the inhibitory effect of acetic acid on carrageenin-induced oedema appeared to be unrelated to the adrenergic neurone-blocking action. The results that adrenergic mechanisms play no significant role in the anti-inflammatory activity of acetic acid.

Adrenergic blockade and the pulmonary vascular response to hypoxia

The role of adrenergic mechanisms in the mediation of the pulmonary vascular response to hypoxia was studied in intact dogs anesthetized with 30 mg/kg sodium pentobarbital. The normal hypoxic response was initially defined in a preparation in which the Pa co 2 , pH and ventilation were controlled at resting levels. The effects of the alpha-adrenergic blocking agent, phenoxybenzamine (2.5 mg/kg) and beta-adrenergic blocking agent, propranolol (2.0 mg/kg) on the hypoxic response were determined when the systemic and pulmonary hemodynamics had stabilized at their new levels. The dosages of blocking agents did not significantly affect the resting hemodynamics and blockade was maintained for the duration of the hypoxic stimulus. Airway and esophageal pressures did not change significantly during the hypoxia. Neither alpha- nor beta-adrenergic blockade altered the hypoxia-induced increases in the pulmonary perfusion pressure, pulmonary blood flow, pulmonary vascular resistance, heart rate and stroke volume. These findings indicate that the pulmonary vascular response to hypoxia in the intact dog is not under sympathetic control, and that the response to hypoxia is a local one.

Central stimulant drugs on avoidance behaviour in hamsters

Summary Central stimulant drugs have been tested on naive hamsters in a shuttle box situation. Facilitating effects are evident after Amphetamine, Methamphetamine and Cocaine administration, while Nicotine, Strichnine, Pentylentetrazol and Caffeine are ineffective. The role of adrenergic mechanism in the action of the facilitating drugs is discussed.

Role of Adrenergic Mechanisms in Development and Therapy of Open-Angled Glaucoma

Role of Adrenergic Mechanisms in Development and Therapy of Open-Angled Glaucoma

Convulsant Action of Polyphenols

IN 1936 Bacq1 demonstrated that, in addition to sensitizing certain smooth muscles of the cat to stimulation of sympathetic nerves and to injected adrenaline, some poly-hydroxylic phenols also possessed convulsant activity. The sensitization was originally attributed to the anti-oxidant properties of the phenolic compounds. More recent studies, however, have indicated that polyphenols augment the peripheral actions of adrenaline by competitive inhibition of catechol-O-methyl transferase (COMT) (refs. 2–4). It has also been suggested that the central effects of polyphenols may be caused by a similar mechanism5. Our study was undertaken to investigate the possible role of adrenergic mechanisms in the central effects of these compounds.

Role of adrenergic mechanisms in the development of motor excitation in rats caused by benactyzine

An investigation was made of behavior reactions of rats under the effects of benactyzine and phenamine, along with the influence exerted by adrenergic blocking agents upon the motor excitation, produced by these preparations. Chlorpromazine was effective in fully eliminating disturbed behavior reactions produced by benactyzine, dihydroergotamine, benzolin (prescolin) while sympatholytin—did this only partially. Under the effect of amphetamine all of the adrenergic blocking agents were capable of restoring the latent reflex period; but stereotype reactions, produced by the action of amphetamine, could be abolished only by chlorpromazine. The above data prove that these disturbances appearing under the effect of the glycolic acid derivatives are caused by the activation of adrenergic mechanisms of the brain.