scispace - formally typeset
Search or ask a question

Showing papers on "Epinephrine published in 1979"


Journal ArticleDOI
TL;DR: During exercise norepinephrine increases and insulin decreases independent of plasma glucose changes whereas receptors sensitive to glucose privation but not to acute changes in insulin levels enhance the exercise-induced secretion of glucagon, epinephrine, growth hormone and cortisol.
Abstract: UNLABELLED The importance of carbohydrate availability during exercise for metabolism and plasma hormone levels was studied. Seven healthy men ran on a treadmill at 70% of individual maximal oxygen uptake having eaten a diet low (F) or high (CH) in carbohydrate through 4 days. At exhaustion the subjects were encouraged to continue to run while glucose infusion increased plasma glucose to preexercise levels. Forearm venous blood, biopsies from vastus muscle and expiratory gas were analyzed. Time to exhaustion was longer in CH- (106 +/- 5 min (S.E.)) than in F-expts. (64 +/- 6). During exercise, overall carbohydrate combustion rate, muscular glycogen depletion and glucose and lactate concentrations, carbohydrate metabolites in plasma, and estimated rate of hepatic glucose production were higher, fat metabolites lower, and the decrease in plasma glucose slower in CH- than in F-expts. Plasma norepinephrine increased and insulin decreased similarly in CH- and F-expts., whereas the increase in glucagon, epinephrine, growth hormone and cortisol was enhanced in F-expts. Glucose infusion eliminated hypoglycemic symptoms but did not substantially increase performance time. During the infusion epinephrine decreased markedly and glucagon even to preexercise levels. Infusion of insulin (to 436% of preexercise concentration) in addition to glucose in F-expts. did not change the plasma levels of the other hormones more than infusion of glucose only but reduced fat metabolites in plasma. At exhaustion muscular glycogen depletion was slow, and the glucose gradient between plasma and sarcoplasma as well as the muscular glucose 6-phosphate concentration had decreased. CONCLUSIONS The preceding diet modifies the energy depots, the state of which (as regards size, receptors and enzymes) is of prime importance for metabolism during prolonged exercise. Plentiful carbohydrate stores favor both glucose oxidation and lactate production. During exercise norepinephrine increases and insulin decreases independent of plasma glucose changes whereas receptors sensitive to glucose privation but not to acute changes in insulin levels enhance the exercise-induced secretion of glucagon, epinephrine, growth hormone and cortisol. Abolition of cerebral hypoglycemia does not inevitably increase performance time, because elimination of the hypoglycemia may not abolish muscular energy lack.

265 citations


Journal ArticleDOI
TL;DR: In this article, the role of anti-insulin hormone actions and interactions in the pathogenesis of stress-induced hyperglycemia was evaluated in normal conscious dogs in doses that were designed to simulate changes observed in severe stress.
Abstract: To evaluate the role of anti-insulin hormone actions and interactions in the pathogenesis of stress-induced hyperglycemia, the counterregulatory hormones, glucagon, epinephrine, and cortisol were infused alone as well as in double and triple combinations into normal conscious dogs in doses that were designed to simulate changes observed in severe stress. Infusion of glucagon, epinephrine, or cortisol alone produced only mild or insignificant elevations in plasma glucose concentration. In contrast, the rise in plasma glucose produced by combined infusion of any two counterregulatory hormones was 50-215% greater (P < 0.005-0.001) than the sum of the respective individual infusions. Furthermore, when all three hormones were infused simultaneously, the increment in plasma glucose concentration (144+/-2 mg/dl) was two- to fourfold greater than the sum of the responses to the individual hormone infusions or the sum of any combination of double plus single hormone infusion (P < 0.001). Infusion of glucagon or epinephrine alone resulted in a transient rise in glucose production (as measured by [3-(3)H]glucose). While glucagon infusion was accompanied by a rise in glucose clearance, with epinephrine there was a sustained, 20% fall in glucose clearance. When epinephrine was infused together with glucagon, the rise in glucose production was additive, albeit transient. However, the inhibitory effect of epinephrine on glucose clearance predominated, thereby accounting for the exaggerated glycemic response to combined infusion of glucagon and epinephrine. Although infusion of cortisol alone had no effect on glucose production, the addition of cortisol markedly accentuated hyperglycemia produced by glucagon and(or) epinephrine primarily by sustaining the increases in glucose production produced by these hormones. The combined hormonal infusions had no effect on beta-hydroxybutyrate concentration. It is concluded that (a) physiologic increments in glucagon, epinephrine, and cortisol interact synergistically in the normal dog so as to rapidly produce marked fasting hyperglycemia; (b) in this interaction, epinephrine enhances glucagon-stimulated glucose output and interferes with glucose uptake while cortisol sustains elevations in glucose production produced by epinephrine and glucagon; and (c) these data indicate that changes in glucose metabolism in circumstances in which several counterregulatory hormones are elevated (e.g., "stress hyperglycemia") are a consequence of synergistic interactions among these hormones.

263 citations


Journal ArticleDOI
TL;DR: The data support the conclusion that bombesin acts within the brain to increase sympathetic outflow resulting in increased adrenalmedullary epinephrine secretion, followed by depression of plasma insulin and elevation of plasma glucagon and glucose.
Abstract: Bombesin acts within the brain to produce a prompt and sustained hyperglycemia, hyperglucagonemia, and relative or absolute hypoinsulinemia. Bombesin does not decrease plasma glucose turnover. Acute adrenalectomy but not hypophysectomy prevents hyperglycemia and hyperglucagonemia after intracisternal administration of bombesin. Administration of bombesin into the lateral ventricle of awake, unrestrained animals results in elevation of plasma glucose, preceded by a significant increase in plasma epinephrine and no increase in plasma norepinephrine or dopamine. Systemic administration of somatostatin prevents bombesin-induced hyperglycemia and hyperglucagonemia. These data support the conclusion that bombesin acts within the brain to increase sympathetic outflow resulting in increased adrenalmedullary epinephrine secretion, followed by depression of plasma insulin and elevation of plasma glucagon and glucose.

197 citations


Journal ArticleDOI
TL;DR: Results suggest that, initially, alpha receptor stimulation with concomitant diastolic pressure elevation is more important to the success of resuscitation than beta receptor stimulation.
Abstract: Successful resuscitation from cardiac arrest in the asphyxiated dog model has been ascribed to the use of artificial ventilation, closed chest cardiac massage, and administration of a vasopressor. Controversy remains over whether the most commonly employed vasopressor, epinephrine, exerts its effects primarily by elevating diastolic pressure and reestablishing coronary flow, or by exciting cardiac pacemaker cells and enhancing myocardial contractility. To observe pure alpha and beta adrenergic receptor influences during resuscitation, three groups (alpha-blocked, beta-blocked, unblocked) of dogs were studied. beta-blocked dogs resuscitated with phenylephrine and unblocked dogs resuscitated with epinephrine experienced 100% successful resumption of spontaneous circulation after 5 min of asphyxia-induced arrest. Only 27% of alpha-blocked animals resuscitated with isoproterenol were successfully revived. The appearance of the ECG during cardiac arrest and resuscitation could in no way be used to predict the outcome of resuscitation attempts. Results suggest that, initially, alpha receptor stimulation with concomitant diastolic pressure elevation is more important to the success of resuscitation than beta receptor stimulation.

186 citations


Journal ArticleDOI
01 Aug 1979-Diabetes
TL;DR: Treatment of insulin-dependent diabetics with a subcutaneous portable insulin infusion system that normalizes plasma glucose results in normalization of the growth hormone and catecholamine response to exercise within 7 to 14 days of institution of treatment.
Abstract: The plasma growth hormone, epinephrine, and norephinephrine responses to cycle ergometer exercise (15 min at 1 W/kg) were examined in 10 juvenile-onset, insulin-dependent diabetics (ages 10–32 yr) during conventional insulin treatment and after 7 and 14 days of treatment with a portable subcutaneous insulin infusion system that normalizes plasma glucose. During conventional insulin treatment (mean plasma glucose, 205 ± 22 mg/dl), the growth hormone response to exercise was sevenfold greater than in normal controls (P

166 citations


Journal ArticleDOI
TL;DR: The results show that urinary sodium excretion as well as blood levels of PRA, norepinephrine, epinephrine, and dopamine were measured in the supine position, at 5, 10, 15, and 20 min of upright posture, and at the end of 40 min of ambulation.
Abstract: The effect of the state of sodium balance on the activity of the sympathetic nervous system has been evaluated previously by measuring urinary catecholamine excretion. Since urinary catecholamine may be affected by factors such as renal function or renal production of catecholamines, blood catecholamines may provide a better index of the activity of the sympathetic nervous system. The present study was undertaken to evaluate the effect of varying sodium intake on blood catecholamines. Thirteen normal subjects were studied for a period of 3 weeks in a metabolic ward. They received during the first, second, and third week 10, 100, and 200 meq sodium/day, respectively. On the seventh day of each week, when the patients had achieved sodium balance, urinary sodium excretion as well as blood levels of PRA, norepinephrine (NE), epinephrine (Ep), and dopamine (D) were measured in the supine position, at 5, 10, 15, and 20 min of upright posture, and at the end of 40 min of ambulation. The results show that: 1) blo...

158 citations


Journal ArticleDOI
TL;DR: It is concluded that trout can respond to changes in oxygen supply by varying the number of secondary lamellae perfused with blood, and that the distribution of blood flow is regulated by cholinergic and adrenergic receptors.
Abstract: Injecting vitally stained blood cells into the ventral aorta of unrestrained, cannulated fish, and rapid freezing in liquid nitrogen, permitted the examination of the effects of oxygen supply, epinephrine and acetylcholine on branchial lamellar perfusion. Compared to the conditions in resting fish in air-saturated water, hypoxia and injection of epinephrine significantly increased the proportion of secondary lamellae receiving stained cells, and acetylcholine caused a significant reduction, but hyperoxia did not significantly affect the proportion of lamellae containing stained cells. Perfusion of the filamental central compartment was not affected by the treatments. It is concluded that trout can respond to changes in oxygen supply by varying the number of secondary lamellae perfused with blood, and that the distribution of blood flow is regulated by cholinergic and adrenergic receptors. It is suggested, however, that lamellar recruitment would not be useful in minimizing the costs of osmo- and iono-regulation.

154 citations


Journal ArticleDOI
TL;DR: Tyrosine injection appears to reduce blood pressure via an action within the central nervous system, since the effect can be blocked by co-administering other large neutral amino acids that reduce tyrosine's uptake into the brain.
Abstract: Administration of L-tyrosine to normotensive or spontaneously hypertensive rats reduces blood pressure. The effect is maximal within 2 hr of injection. In spontaneously hypertensive rats, a dose of 50 mg/kg, intraperitoneally, reduces blood pressure by about 12 mm Hg (1 mm Hg = 1.33 x 10(2) pascals); a dose of 200 mg/kg produces the maximal effect, a reduction of about 40 mm Hg. Tryptophan injection (225 mg/kg) also lowers blood pressure in spontaneously hypertensive rats, but only by about half as much as an equivalent dose of tyrosine. Other amino acids tested (leucine, isoleucine, valine, alanine, arginine, and aspartate) do not affect blood pressure. Tyrosine injection appears to reduce blood pressure via an action within the central nervous system, since the effect can be blocked by co-administering other large neutral amino acids that reduce tyrosine's uptake into the brain. That tyrosine's antihypertensive action is mediated by an acceleration in norepinephrine or epinephrine release within the central nervous system is suggested by the concurrent increase that its injection produces in brain levels of methoxyhydroxyphenylethylglycol sulfate.

150 citations


Journal ArticleDOI
TL;DR: It is concluded that endotracheally and intravenously administered epinephrine rapidly reach maximum blood levels although there are differences in kinetics between the two routes.
Abstract: The blood levels of epinephrine and its metabolites which were obtained when the drug was given by both the intravenous (IV) and endotracheal (ET) routes were compared. Anesthetized dogs were subjected to radioactive epinephrine in doses of 0.005, 0.03, 0.06, and 0.09 mg/kg administered both intravenously and endotracheally. Blood levels were obtained at 0.25, 0.75, 1.5, 3, 5, 10 and 30 minutes following injection and analyzed by thin layer chromatography. The maximum measured concentration following IV injection was observed at 15 seconds. Epinephrine was rapidly metabolized with 20% of the original concentration detected at 5 minutes following IV injection. When the drug was given by the ET route, the maximum measured concentration was similarly observed at 15 seconds. Following ET installation, initial blood concentrations are sustained over a much longer period of time and 80% of the initial concentration was detected at 5 minutes. Maximum concentrations are approximately one-tenth of those achieved with an equal IV dosage. It is concluded that endotracheally and intravenously administered epinephrine rapidly reach maximum blood levels although there are differences in kinetics between the two routes.

136 citations


Journal ArticleDOI
TL;DR: It is demonstrated that adaptive changes in the cardiovascular and sympatho-adrenal medullary systems of repeatedly immobilized rats are greater in SHR than in WKY rats.
Abstract: Blood pressure, heart rate, and circulating levels of norepinephrine, epinephrine, and corticosterone were measured before and during the first or seventh period of immobilization stress (150 min per day) in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive male rats. A catheter was inserted into the tail artery of each rat to permit direct measurement of blood pressure and heart rate and serial sampling of blood in conscious, unhandled animals. During the first immobilization, SHR rats had significantly higher circulating levels of norepinephrine, epinephrine, and corticosterone than did WKY rats. One day after the sixth immobilization, basal levels of norepinephrine and epinephrine were significantly higher and mean blood pressure was significantly lower in repeatedly stressed SHRs compared to unstressed SHRs. In addition, adaptation to the repeated stress in SHRs was attended by reduced adrenomedullary secretion and an increased blood pressure response. These results demonstrate that adaptive changes in the cardiovascular and sympatho-adrenal medullary systems of repeatedly immobilized rats are greater in SHR than in WKY rats.

132 citations


Journal ArticleDOI
TL;DR: In man hyperepinephrinemia within the physiological range caused sustained suppression of glucose clearance but only a transient increase in glucose production, and epinephrine can serve as a physiological regulator of glucose homeostasis in man both by increasing glucose production and by decreasing glucose clearance.
Abstract: Normal subjects were infused 1) with epinephrine (50 ng/(kg.min)) for 180 min followed by epinephrine plus glucagon (3 ng/(kg.min)) for 60 min after which the epinephrine infusion rate was increased (125 ng/(kg.min)) or 2) with epinephrine plus somatostatin (500 microgram/h) for 180 min. Epinephrine increased glucose production and plasma glucagon transiently but caused persistent suppression of glucose clearance and sustained hyperglycemia (despite increased plasma insulin and gluconeogenic substrates); glucose production increased again on addition of glucagon and on increasing the epinephrine infusion rate. During epinephrine plus somatostatin, glucose production still increased transiently, but further suppression of glucose clearance caused more marked hyperglycemia. In conclusion, 1) in man hyperepinephrinemia within the physiological range caused sustained suppression of glucose clearance but only a transient increase in glucose production; 2) this transient hepatic response a) was not due to glycogen or substrate depletion, b) occurred without changes in plasma glucagon or insulin, c) was specific for epinephrine but permitted subsequent responses to changes in plasma epinephrine; 3) epinephrine can serve as a physiological regulator of glucose homeostasis in man both by increasing glucose production and by decreasing glucose clearance.

Journal ArticleDOI
TL;DR: It is concluded that the lungs play a significant role in the inactivation of circulating norepinephrine in man and this metabolic function of the lungs appears to be lost in pulmonary hypertension.
Abstract: We directly measured the net pulmonary extraction of circulating norepinephrine, epinephrine and dopamine in control patients and patients with primary or secondary pulmonary hypertension. Mixed pulmonary artery norepinephrine, epinephrine and dopamine were 314 +/- 13 pg/ml, 102 +/- 9 pg/ml, 51 +/- 5 pg/ml, respectively, for the control group; values were similar in patients with pulmonary hypertension. The pulmonary extraction of norepinephrine was 25.4 +/- 2.6% (clearance 266 +/- 62 ng/min) in control patients; epinephrine and dopamine were not extracted. There was no net extraction or production of any of the three catecholamines by the lungs in any of the patients with pulmonary hypertension. We conclude that the lungs play a significant role in the inactivation of circulating norepinephrine in man. This metabolic function of the lungs appear to be lost in pulmonary hypertension.

Journal ArticleDOI
TL;DR: Coronary occlusion in the conscious dog results in immediate haemodynamic deterioration and activation of the sympathetic nervous system, with a strong correlation between the two suggesting thatactivation of the sympathy nervous system by haemodynamics reflexes may be of importance in theconscious canine model.
Abstract: In order to define the temporal and quantitative relationship between the plasma concentrations of catecholamines and the extent and location of myocardial infarction, conscious dogs underwent left anterior descending or circumflex coronary occlusion with continuous haemodynamic monitoring. Plasma noradrenaline and adrenaline concentrations were measured by the serial isotope derivative method and infarction size by the creatine kinase depletion method. Rapid increases in plasma catecholamines were seen within 1 min of coronary occlusion. Within the first hour profound elevations of plasma adrenaline (10 fold) and noradrenaline (3 fold) occurred, with peak adrenaline and noradrenaline levels correlated to infarction size determined 24 h later in anterior (r =0.71; r =0.83) and posterior (r =0.89, r =0.78) infarctions. Cardiac output and mean systemic arterial blood pressure were inversely related to adrenaline (r =0.88, r =0.73) and noradrenaline (r =0.94, r =0.73) and deterioration in haemodynamics was always noted simultaneously with or preceding increases in plasma catecholamine concentrations. There were no significant differences in plasma catecholamines dependent on location of infarction. Thus, coronary occlusion in the conscious dog results in immediate haemodynamic deterioration and activation of the sympathetic nervous system, with a strong correlation between the two suggesting that activation of the sympathetic nervous system by haemodynamic reflexes may be of importance in the conscious canine model. The degree of autonomic activation within the first hour after occlusion appears to be related to the ultimate size of infarction, possibly because of the relationship between impairment of ventricular performance and infarct size.

Journal ArticleDOI
TL;DR: Sympathetic nervous system activity, as measured by [(3)H]NE turnover in the heart, decreases in fasting pregnant rats despite hypoglycemia, a response similar to that seen in fasting nonpregnant animals where plasma glucose is maintained above 50 mg/dl.
Abstract: The pattern of urinary catecholamine excretion in fasting differs in pregnant and nonpregnant rats, which suggests that the sympathoadrenal response to fasting is altered by pregnancy. In fasting nonpregnant animals, urinary norepinephrine (NE) excretion decreases and epinephrine (E) excretion remains unchanged, whereas the excretion of both catecholamines rises significantly with refeeding. In contrast, fasting third-trimester pregnant rats exhibit a 420% increase in urinary E and a 345% increase in urinary NE, elevations which fall with refeeding. Specific evaluation of sympathoadrenal activity in fasting pregnant rats reveals stimulation of the adrenal medulla and suppression of sympathetic nerves. In fasting third-trimester rats the adrenal content of E is 37% lower in innervated adrenals as compared with contralateral denervated glands, which indicates the presence of neurally-mediated adrenal medullary activation. Adrenalectomy completely abolishes the fasting-induced rise in urinary E and NE in pregnant rats. Studies with 2-deoxy-D-glucose suggest that stimulation of the adrenal medulla results from hypoglycemia, which is present after 3 d of fasting in pregnant rats (plasma glucose 36.7 mg/dl). Sympathetic nervous system activity, as measured by [(3)H]NE turnover in the heart, decreases in fasting pregnant rats despite hypoglycemia, a response similar to that seen in fasting nonpregnant animals where plasma glucose is maintained above 50 mg/dl. The calculated NE turnover rate is 44% lower in 2-d fasted pregnant rats than in fed pregnant animals (17.6 +/- 1.3 vs. 31.3 +/- 1.8 ng NE/heart per h, respectively). Thus adrenal medullary and sympathetic nervous system responses in fasting pregnant rats appear to be dissociated, which suggests that diet-induced changes in sympathetic activity and stimulation of the adrenal medulla by hypoglycemia may be independently regulated.

Journal ArticleDOI
TL;DR: Both the relative sensitivities of SCC to various adrenergic agonists and the effect of propranolol suggest that Cl-secretory process is highly sensitive to beta-adrenergic receptor stimulation.
Abstract: The action of adrenergic agonists on ion fluxes across the epithelium of the canine trachea was determined. Isolated sheets of tracheal mucosal membranes were mounted in Ussing-type chambers, bathed with Krebs-Henseleit solution at 37 degrees C, pH 7.4, and gassed with 5% CO2 Iin oxygen. Various adrenergic agents, when added to the bathing medium elevated short-circuit current (SCC) (isoproterenol greater than epinephrine greater than norepinephrine greater than phenylephrine). Propranolol (10(-6) M) decreased SCC response to epinephrine. Epinephrine (1mM) increased both unidirectional 36Cl fluxes; net 36Cl secretion toward the lumen increased from 2.01 +/- 0.52 to 3.20 +/- 0.46 mueg/cm2.h (P less than 0.05); 22Na flux did not change. In epinephrine-stimulated tissues, propranolol (1mM) abolished net 36Cl secretion. The SCC response to epinephrine was blunted in the absence of Na from the submucosal reservoir; this blunting suggests that Cl entry across the basal membrane is coupled with Na. Both the relative sensitivities of SCC to various adrenergic agonists and the effect of propranolol suggest that Cl-secretory process is highly sensitive to beta-adrenergic receptor stimulation. Epinephrine increased cell membrane permeability to Cl and probably stimulated a specific Cl pump.

Journal Article
TL;DR: The degree of corticosteroid/amine potentiation was greater for epinephrine than for norepinephrine and greater in the digital vein than in the corresponding artery from the same animal.
Abstract: Spirally cut digital arteries and veins were mounted isotonically in organ baths containing oxygenated Krebs' Q-Henseleit solution. Twelve arterial and 12 venous preparations all contracted dose dependently when epinephrine, norepinephrine, serotonin, or histamine were added to the bathing fluid. Addition of hydrocortisone or betamethasone alone did not cause contractions in any of the tissues tested. However, when hydrocortisone or betamethasone was added to vessel strips that were partially contracted (40% to 60% maximal) by epinephrine, norepinephrine, or serotonin, each vessel strip invariably underwent an additional contraction. In venous and arterial strips, dose-response curves to epinephrine, norepinephrine, serotonin, or histamine were established in the absence and in the presence of corticosteroid. Effects of the amines, except histamine, were markedly potentiated. The degree of corticosteroid/amine potentiation was greater for epinephrine than for norepinephrine and greater in the digital vein than in the corresponding artery from the same animal. Betamethasone was more potent than hydrocortisone.

Journal ArticleDOI
TL;DR: The view that the central sympathetic nervous system is involved in the pathogenesis of primary hypertension, particularly in younger patients, is supported, as the low CSF norepinephrine and epinephrine, despite markedly increased plasma NE and epinphrine, indicate a blood-brain barrier for these neurohormones.
Abstract: To test whether central neurogenic factors participate in blood pressure elevation in primary hypertension, we studied the concentrations of: norepinephrine, epinephrine and dopamine-beta-hydroxylase (DBH) in cerebrospinal fluid (CSF); and norepinephrine, epinephrine, DBH and plasma renin activity (PRA) in plasma of 22 subjects (seven with primary hypertension, 11 normotensive patients with non-systemic neurological disorders, and four with secondary hypertension). Plasma and CSF norepinephrine (NE) were increased in primary hypertensives compared to normotensives. Cerebrospinal fluid norepinephrine was related to diastolic blood pressure, and systolic blood pressure when normotensive and primary hypertensives were taken together. The CSF norepinephrine of primary hypertensive patients was correlated with natural log PRA. The CSF norepinephrine was correlated inversely with age in primary hypertensive patients but not in the normotensive subjects. The low CSF norepinephrine and epinephrine, despite markedly increased plasma NE and epinephrine, in two patients with pheochromocytoma, indicate a blood-brain barrier for these neurohormones. The observations support the view that the central sympathetic nervous system is involved in the pathogenesis of primary hypertension, particularly in younger patients.

Journal ArticleDOI
TL;DR: Data showing a significant reduction in intraocular pressure as a result of ocular instillation of timolol are presented and reduction of the rate of aqueous formation appears to be the mechanism of action.

Journal ArticleDOI
TL;DR: Increases in plasma concentration of dopamine in response to standing are comparable to those observed for norepinephrine and epinephrine, and maneouvres which are associated with increases in sympathetic activity areassociated with parallel increases in each of the three catecholamines.

Journal ArticleDOI
TL;DR: In rats, both forced immobilization and 2-deoxyglucose (2DG) administration evoke increases in sympatho-adrenal medullary release of catecholamines and adrenal cortical secretion of corticosterone, but plasma levels of norepinephrine were increased only at the highest dose of 2DG, and there was a clear relationship between dose and increases in epinephrine.
Abstract: In rats, both forced immobilization and 2-deoxyglucose (2DG) administration evoke increases in sympatho-adrenal medullary release of catecholamines and adrenal cortical secretion of corticosterone. To examine the specificity and mediation by the central nervous system of these responses, plasma levels of epinephrine (from the adrenal medulla), norepinephrine (from sympathetic nerves), and corticosterone were determined during immobilization and after ip or intracerebroventricular administration of 2DG. After 2DG, plasma levels of epinephrine reached a peak within 15 min, while those of corticosterone were maximal at about 1 h. There was a clear relationship between dose of 2DG and the increases in epinephrine and corticosterone, but plasma levels of norepinephrine were increased only at the highest dose (1000 mg/kg) of 2DG. Severing the splanchnic nerve prevented the elevation in levels of epinephrine but did not alter the increase in corticosterone. The dose of 2DG (500 mg/kg) which elicited the same cor...

Journal ArticleDOI
TL;DR: It is concluded that β-adrenoceptors of the β 2 type are present on adrenergic neurons innervating the rat portal vein and Activation of these receptors results in an enhancement of the electrically induced release of NE.

Journal ArticleDOI
TL;DR: The results indicate that the adrenal medulla of rats is a significant source of circulating NE during mildly and intensely stressful stimulation, and activity during footshock stress was greater in rats with an intact sympathetic nervous system.

Journal ArticleDOI
TL;DR: The results support the view that both epinephrine and norepinephrine may act as circulating hormones, because vascular and metabolic effects of both amines were seen at plasma concentrations encountered during various kinds of stress in animals and man.
Abstract: Vascular and metabolic effects of circulating epinephrine and norepinephrine have been studied in relation to the plasma concentration of these amines in dogs. Intravenous infusion of epinephrine or norepinephrine (0.1, 0.5, and 2.5 nmol x kg-1 x min-1) raised the plasma concentration of the infused amine by 2.5 , 13, and 63 nM from resting levels of 2.4 and 3.6 nM, respectively. Blood flow to isolated adipose tissue; skeletal muscle preparations; and plasma levels of glycerol, glucose, and cyclic AMP were measured. Epinephrine and norepinephrine displayed a distinct selectivity with regard to both vascular and metabolic effects. Epinephrine caused significant vasoconstriction in adipose tissue already at a plasma concentration of 5 nM, whereas no significant effect was seen on skeletal muscle vascular resistance. Norepinephrine, on the other hand, caused significant vasoconstriction in skeletal muscle at 5 nM but had no vasoconstrictor effect in adipose tissue. Epinephrine was more potent than norepinephrine in increasing plasma cyclic AMP and glucose, whereas the converse was true for plasma glycerol. Epinephrine had significant effects on plasma cyclic AMP at 5 nM and on plasma glucose and glycerol at 15 nM. Norepinephrine, on the other hand, had significant effects on plasma glycerol at 5 nM, plasma cyclic AMP at 15 nM and plasma glucose only at 65 nM. It is suggested that these response patterns are related to a preferential action of epinephrine on beta 2-adrenoceptors and a preferential action of norepinephrine on beta 1-adrenoceptors. Our results support the view that both epinephrine and norepinephrine may act as circulating hormones, because vascular and metabolic effects of both amines were seen at plasma concentrations encountered during various kinds of stress in animals and man.

Journal ArticleDOI
TL;DR: Measurement of plasma norepinephrine and epinephrine concentrations in the conscious, unrestrained rat yielded values of 138±10 and 55±8 pg/ml, respectively.

Journal ArticleDOI
TL;DR: The aim of this study was to explain the unresponsiveness of rabbit perirenal adipose tissue to epinephrine, and the loss of beta-adrenergic responsiveness towards epinphrine in the aging rabbit is linked to the involvement of an increased alpha-adRenergic responsiveness.

Journal Article
TL;DR: It is concluded that verapamil acts as an α-adrenergic antagonist in rat liver and has no detectable effects on transmembrane Ca2+ flux.
Abstract: The effects of verapamil on basal and hormone-induced glycogenolysis, phosphorylase activation, 45Ca efflux and calcium content in isolated rat liver parenchymal cells were studied. The agent inhibited the stimulatory effects of epinephrine and phenylephrine on all these parameters, but did not modify the actions of vasopressin, glucagon, exogenously-added cAMP and low concentrations of the ionophore A23187. It inhibited calcium uptake due to high concentrations (>10-6 M) of A23187, but did not modify the activation of phosphorylase. Verapamil inhibited the binding of 4 x 10-8 M [3H]epinephrine to liver plasma membranes in the presence of the β-adrenergic blocker, propranolol. The concentration for half-maximal inhibition of binding (2 x 10-5 M) was very similar to that producing half-maximal inhibition of the effects of 4 x 10-8 M epinephrine on phosphorylase activation or calcium efflux in hepatocytes. Verapamil was without significant effect on the reaccumulation of calcium by cells previously depleted of calcium by treatment with EGTA. It is concluded that verapamil acts as an α-adrenergic antagonist in rat liver and has no detectable effects on transmembrane Ca2+ flux.

Journal ArticleDOI
01 Jun 1979-Diabetes
TL;DR: It is suggested that a fall in blood glucose per se may reverse insulin-induced inhibition of glucose production independent of a rise in counterregulatory hormones and that the insulin antagonist effect of counter Regulatory hormones is modulated, at least in part, by blood glucose concentration.
Abstract: Continuous, low dose, insulin infusion in conscious dogs produced moderate hypoglycemia but only a transient fall in glucose production that rose towards preinfusion levels 20 to 30 min before any detectable increase in plasma counterregulatory hormones. Addition of epinephrine or glucagon to the insulin infusion prevented the fall in glucose production throughout the experiment but only partially diminished the hypoglycemic response. When hypoglycemia was prevented by a variable glucose infusion, neither epinephrine nor glucagon was able to counteract the suppressive effect of insulin on glucose output. These findings suggest that a fall in blood glucose per se may reverse insulin-induced inhibition of glucose production independent of a rise in counterregulatory hormones and that the insulin antagonist effect of counterregulatory hormones is modulated, at least in part, by blood glucose concentration.

Journal ArticleDOI
TL;DR: Nondiabetic patients with hypoadrenergic postural hypotension due to documented or probable central nervous system lesions exhibited normal responses to cholinergic stimulation produced in this fashion demonstrating the presence of intact sympathetic postganglionic neurons and adrenal medullae in these patients and providing further support for the conceptual soundness of this approach to the study of human adrenergic physiology and pathophysiology.
Abstract: Amplification of endogenous cholinergic activity—produced by the intravenous injection of edrophonium, an acetylcholinesterase inhibitor which does not enter the central nervous system, into normal subjects—resulted in significant and briefly sustained increments in the plasma concentrations of norepinephrine (153±15−234±29 pg/ml, P < 0.01) and epinephrine (16±3−34±5 pg/ml, P < 0.01) measured with a single-isotope derivative method. These increments were not attributable to reflex responses to hemodynamic changes and similar increments in plasma norepinephrine occurred in adrenalectomized (epinephrine deficient) patients. Thus, cholinergic activation results in direct stimulation of sympathetic postganglionic neurons, with augmented norepinephrine release, and of the adrenal medullae, with augmented epinephrine release, in man. Four diabetic patients with hypoadrenergic postural hypotension exhibited blunted sympathetic postganglionic neural responses, and normal adrenomedullary responses, to cholinergic stimulation (and to standing) indicative of the presence of a sympathetic postganglionic axonal lesion in diabetic adrenergic neuropathy. Nondiabetic patients with hypoadrenergic postural hypotension due to documented or probable central nervous system lesions exhibited normal responses to cholinergic stimulation produced in this fashion demonstrating the presence of intact sympathetic postganglionic neurons and adrenal medullae in these patients and providing further support for the conceptual soundness of this approach to the study of human adrenergic physiology and pathophysiology.

Journal Article
TL;DR: The effects of prostaglandin E1 on cAMP, cAMP-dependent protein kinase, glycogen phosphorylase, and contractile force have been investigated in the isolated perfused rat heart, and compared to the effects of epinephrine.
Abstract: The effects of prostaglandin E1 (PGE1) on cAMP, cAMP-dependent protein kinase, glycogen phosphorylase, and contractile force have been investigated in the isolated perfused rat heart, and compared to the effects of epinephrine. In this heart preparation both PGE1 and epinephrine produced rapid, concentration-dependent increases in cAMP and the cAMP-dependent protein kinase activity ratio. When dosages were adjusted to give equal increases in the protein kinase activation ratio from a basal value of 0.15 to as high as 0.40, only epinephrine produced a significant increase in contractile force or phosphorylase activity. Neither the α-adrenergic agonist phenylephrine nor ionophore A-23187 altered the inability of PGE1 to augment phosphorylase activity or force. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine potentiated the effect of PGE1 on cAMP and protein kinase activity. When used at concentrations of 10 µM or less, PGE1 failed to increase phosphorylase kinase activity even though it did produce a 2-fold increase in the cAMP-dependent protein kinase activity ratio. If very high protein kinase activity ratios were generated by using very high PGE1 levels (100 µM) or PGE1 in combination with isobutylmethylxanthine, increases in phosphorylase kinase activity were observed. This activation was, however, less than that observed when epinephrine was used to produce a similar protein kinase activation state and was accompanied by a slight increase in phosphorylase activity. When used together, PGE1 and epinephrine produced partially additive effects on cAMP and protein kinase activity and approximately the same increase in phosphorylase activity as did epinephrine when used alone. If very high cAMP levels or protein kinase activity ratios were produced by infusion of epinephrine plus 3-isobutyl-1-methylxanthine, PGE1 produced no further increase in either parameter.

Journal ArticleDOI
01 May 1979-Medicine
TL;DR: It is presented a concept that, in familial pheochromocytoma, the metabolism of catecholamines is altered by the process of aging, and that this change modifies the clinical presentations of the disease.