Showing papers on "Epinephrine published in 1983"
TL;DR: Beta 2-receptor stimulation is required for catecholamine-induced hypokalemia to occur and can be prevented by selective beta 2 blockade, which does not abolish the inotropic effect of epinephrine.
Abstract: To determine whether epinephrine-induced hypokalemia is due to beta2-adrenoceptor stimulation, and whether hypokalemia can occur at physiologic concentrations of the agonist, epinephrine was infused into six normal volunteers at a rate of 0.1 microgram per kilogram of body weight per minute. The circulating epinephrine concentration was increased to 1.74 +/- 0.65 ng per milliliter, plasma potassium was reduced by 0.82 +/- 0.19 meq per liter, plasma insulin fell by 12 +/- 4 mU per liter, plasma renin activity was elevated, and tachycardia occurred. Isoproterenol infused at 0.02 micrograms per kilogram per minute caused similar tachycardia (25 beats per minute) and elevation in plasma renin activity (6.0 to 6.5 ng per milliliter per hour), but no hypokalemia. The difference in responses to the two catecholamines was ascribed to the relative beta2-selectivity of epinephrine. This hypothesis was tested in six subjects given infusions of epinephrine (0.05 micrograms per kilogram per minute) after administration of either 2.5 or 5 mg of ICI 118551--a selective beta2-receptor antagonist--or placebo. After placebo, epinephrine infusion elevated the circulating epinephrine concentration and reduced plasma potassium; hypokalemia was prevented by the beta2-antagonist. This drug only partially inhibited the rises in plasma renin and glucose and the shortening of systolic time intervals; there was no tachycardia. Fifteen-fold to 30-fold increases in circulating epinephrine concentration appear to cause hypokalemia by a specific beta2-receptor effect distinct from other actions of epinephrine. This phenomenon may be of physiologic importance after severe myocardial infarction, when similar increases in plasma epinephrine have occurred.
603 citations
TL;DR: The preponderance of literature on the subject supports the hypothesis that increased plasma catecholamine concentrations occur in some patients with essential hypertension, and is consistent with a pathophysiologic role for increased sympathetic neural activity in this subgroup of hypertensive patients.
Abstract: Of 78 comparative studies of plasma catecholamines in patients with essential hypertension and in normotensive controls, most reported higher catecholamine levels in the hypertensives, although only about 40% of the studies were positive (reporting statistically significant hypertensive-normotensive differences). Although there was dramatic variability in catecholamine values within and across studies, virtually all studies of norepinephrine in young, consistently hypertensive patients were positive. The likelihood that a study was positive with respect to norepinephrine was independent of the likelihood with respect to epinephrine, so that total catecholamine values, or else the sum of norepinephrine plus epinephrine, differentiated hypertensives from normotensives to a greater extent than levels of either substance alone. The preponderance of literature on the subject supports the hypothesis that increased plasma catecholamine concentrations occur in some patients with essential hypertension. Elevated plasma norepinephrine in relatively young, established hypertensive patients is consistent with a pathophysiologic role for increased sympathetic neural activity in this subgroup.
586 citations
TL;DR: It is concluded that impaired A-cell secretion is the predominant mechanism for the delayed glucose recovery after hypoglycemia in diabetic patients without insulin antibodies and normal epinephrine responses, which appears to be acquired defects that develop subsequent to B-cell failure.
Abstract: To evaluate the roles of counterregulatory hormones and insulin antibodies in the impairment of plasma glucose recovery from hypoglycemia in diabetes mellitus, and to assess the relationship between the glucagon response and duration of the disease, 21 insulin-dependent diabetic patients and 10 nondiabetic subjects were studied. The diabetics consisted of 5 patients with recent onset of diabetes (less than 1 mo); 11 with 2.6 +/- 0.3 (mean +/- SEM) yr duration of diabetes, 5 of whom had insulin antibodies; and 5 patients with long-term diabetes (21 +/- 3 yr), insulin antibodies, and autonomic neuropathy. During insulin-induced hypoglycemia (28 mU/m2 X min for 60 min) in patients with recent-onset diabetes, plasma free insulin, glucose, and counterregulatory hormone concentrations did not differ from those of nondiabetic subjects. In patients with insulin antibodies, the disappearance of insulin after insulin infusion was delayed, and both restitution of normoglycemia and plasma glucagon response were blunted compared with patients without antibodies. When glucagon was infused (80-130 ng/m2 X min) during hypoglycemia in diabetics with impaired glucagon responses in order to simulate normal glucagon responses, plasma glucose recovery was normalized in patients without antibodies but not in those with antibodies. In patients with long-standing diabetes, restitution of normoglycemia was further impaired and this was associated with an absent plasma glucagon response and a diminished plasma epinephrine response. Plasma glucagon responses to hypoglycemia were inversely correlated to the duration of diabetes (r = -0.943; P less than 0.0005). It is concluded that impaired A-cell secretion is the predominant mechanism for the delayed glucose recovery after hypoglycemia in diabetic patients without insulin antibodies and normal epinephrine responses. Slowed disappearance of insulin due to the presence of insulin antibodies further delays the restoration of normoglycemia. Patients with long-standing diabetes and autonomic neuropathy exhibit decreased epinephrine secretion, which leads to an additional retardation of glucose recovery. Since plasma glucagon and epinephrine responses to hypoglycemia were normal at the onset of diabetes but diminished in long-term diabetes, it appears that the impaired glucagon and epinephrine responses to hypoglycemia are acquired defects that develop subsequent to B-cell failure.
428 citations
Journal Article•
TL;DR: The administration of physiologic doses of epinephrine results in changes in the relative proportions of lymphocyte subsets in peripheral blood, in addition to reduced mitogen responsiveness as reported previously.
Abstract: We have previously demonstrated that mitogen responsiveness of mononuclear cells (MNC) from peripheral blood is reduced after a single injection of epinephrine to human subjects. The purpose of the present study was to characterize the relative distributions of MNC subsets after epinephrine administration using monoclonal antibodies and conventional cell markers. The absolute number of circulating MNC increased 64% within 30 min after injection of epinephrine, and returned to baseline by 2 hr. Analysis of MNC subsets revealed that there were no changes in the relative percentages of total T lymphocytes [T3+ cells, or neuraminidase-treated sheep red blood cell rosettes (EN-rosettes)], B lymphocytes (B1+, or cells with surface-bound immunoglobulin), or monocytes (by morphologic criteria) after epinephrine administration. The percentage of inducer T cells (T4+) declined at 30 and 60 min postinjection. Overall, the percentage of suppressor/cytotoxic T cells (T8+) did not change after injection of epinephrine; however, analysis of individual subjects revealed opposing responses of this subset. The T4:T8 ratio was 2.19 before injection, declined to 1.56 at 60 min, then increased to 3.10 2 hr postinjection. The percentage of natural killer/killer cells (HNK-1+) increased from a baseline of 15.5% before epinephrine injection to 29.6% at 30 min postinjection, then declined to 11.4% at 2 hr. Therefore, the administration of physiologic doses of epinephrine results in changes in the relative proportions of lymphocyte subsets in peripheral blood, in addition to reduced mitogen responsiveness as reported previously.
250 citations
TL;DR: The results indicate that the effects of insulin on central catecholamines are elicited by its action in the brain and induced a dose-related increased release of norepinephrine, epinephrine and dopamine from hypothalamic slices.
190 citations
TL;DR: Lumbar epidural anesthesia during labor reduces maternal epinephrine levels, probably by eliminating the psychological and physical stress associated with painful uterine contractions or by denervating the adrenal medulla.
176 citations
TL;DR: The results suggest that epinephrine and other catecholamines may act as growth factors for aortic SMC, at least in rat, mostly through adrenoreceptors, and this mitogenic response of SMC to catechols was specific since it could be blocked by adrenergic blocking agents.
Abstract: The effect of epinephrine was tested on the proliferation of rat arterial smooth muscle cells (SMC) in secondary cultures. Epinephrine added daily to the culture medium caused a striking stimulation of growth. The effect increased with time and was dose-dependent. Maximal stimulation was observed at a concentration of 10(-5) M and after 72 hours. At higher concentrations (10(-3) M) epinephrine exhibited toxic effects on SMC. When SMC were maintained quiescent by deprivation of serum, the subsequent addition of epinephrine required serum to significantly enhance growth. This growth stimulation increased with serum concentration (from 0.1% to 10%). All the adrenergic agonists tested were found to stimulate SMC growth, with an activity classified by decreasing order as follows: norepinephrine greater than epinephrine greater than isoproterenol. Finally, this mitogenic response of SMC to catecholamines was specific since it could be blocked by adrenergic blocking agents, phentolamine being more efficient than propranolol in that connection. The results suggest that epinephrine and other catecholamines may act as growth factors for aortic SMC, at least in rat, mostly through adrenoreceptors.
170 citations
Journal Article•
TL;DR: Data suggest that the reduction in mitogen responsiveness after epinephrine is the result of changes in the distribution of lymphocyte subclasses in peripheral blood.
Abstract: A single subcutaneous injection of 0.2 mg epinephrine into healthy human subjects caused a transient lymphocytosis in peripheral blood. Mononuclear cells (MNC), isolated at various times after epinephrine administration, were cultured in the presence of mitogens. The blastogenic responses to pokeweed mitogen (PWM) and phytohemagglutinin (PHA) were significantly reduced for up to 60 min post-epinephrine (p less than 0.05); the response to concanavalin A (Con A) was reduced in the 15-min samples only. All responses returned to pre-injection levels by 120 min post-injection. Removal of adherent monocytes from MNC isolates before culture did not restore normal mitogen responsiveness. When MNC were cultured in the absence of mitogens, there was no difference in survival between pre- and post-epinephrine samples. Incubation of untreated MNC for 2 hr or 18 hr in vitro with various concentrations of epinephrine (10(-5) to 10(-1) mg/ml) had no effect upon the subsequent blastogenic response to mitogens. Other workers have reported that epinephrine administration causes alterations in the composition of the circulating lymphocyte pool. Taken together, these data suggest that the reduction in mitogen responsiveness after epinephrine is the result of changes in the distribution of lymphocyte subclasses in peripheral blood.
157 citations
TL;DR: It is concluded that epinephrine is a potent stimulator of gluconeogenesis in humans, and this effect is primarily mediated by mobilization of lactate and alanine from extrasplanchnic tissues.
Abstract: To evaluate the contribution of gluconeogenesis to epinephrine-stimulated glucose production, we infused epinephrine (0.06 micrograms X kg-1 X min-1) for 90 min into normal humans during combined hepatic vein catheterization and [U-14C]alanine infusion. Epinephrine infusion produced a rise in blood glucose (50-60%) and plasma insulin (30-40%), whereas glucagon levels increased only at 30 min (19%, P less than 0.05). Net splanchnic glucose output transiently increased by 150% and then returned to base line by 60 min. In contrast, the conversion of labeled alanine and lactate into glucose increased fourfold and remained elevated throughout the epinephrine infusion. Similarly, epinephrine produced a sustained increase in the net splanchnic uptake of cold lactate (four- to fivefold) and alanine (50-80%) although the fractional extraction of both substrates by splanchnic tissues was unchanged. We conclude that a) epinephrine is a potent stimulator of gluconeogenesis in humans, and b) this effect is primarily mediated by mobilization of lactate and alanine from extrasplanchnic tissues. Our data suggest that the initial epinephrine-induced rise in glucose production is largely due to activation of glycogenolysis. Thereafter, the effect of epinephrine on glycogenolysis (but not gluconeogenesis) wanes, and epinephrine-stimulated gluconeogenesis becomes the major factor maintaining hepatic glucose production.
149 citations
TL;DR: Hepatocytes from juvenile male rats showed a 12-fold elevation of cAMP in response to epinephrine, which was mediated by beta 2-adrenergic receptors, which suggest that, in maturity, hepatic alpha 1-receptors become linked to 2 separate transduction mechanisms, namely Ca2+ mobilization and cAMP generation.
137 citations
TL;DR: High levels of parathyroid hormone have direct effects on skeletal muscle protein, amino acid, and cyclic nucleotide metabolism in muscle of normal but not uremic animals, which is suggested to account in part for the muscle dysfunction and wasting of primary hyperparathyroidism and chronic uremia.
Abstract: Because prominent skeletal muscle dysfunction and muscle wasting are seen in both chronic uremia and in primary hyperparathyroidism, and because markedly elevated parathyroid hormone levels occur in both disorders, potential effects of parathyroid hormone on skeletal muscle protein, amino acid, and cyclic nucleotide metabolism were studied in vitro using isolated intact rat epitrochlearis skeletal muscle preparations. Intact bovine parathyroid hormone and the synthetic 1-34 fragment of this hormone stimulated the release of alanine and glutamine from muscle of control but not from chronically uremic animals. This stimulation was dependent upon the concentration of parathyroid hormone added: At 10(5) ng/ml parathyroid hormone increased alanine release 84% and glutamine release 75%. Intracellular levels of alanine and glutamine were not altered by parathyroid hormone. Increasing concentrations of the 1-34 polypeptide decreased [(3)H]leucine incorporation into protein of muscles from both control and uremic animals. Using muscles from animals given a pulse-chase label of [guanido-(14)C]arginine in vivo, parathyroid hormone increased the rate of loss of (14)C label from acid-precipitable protein during incubation and correspondingly increased the rate of appearance of this label in the incubation media. Parathyroid hormone increased muscle cAMP levels by 140% and cGMP levels by 185%, but had no effect on skeletal muscle cyclic nucleotide phosphodiesterase activities as assayed in vitro. Adenylyl cyclase activity in membrane preparations from control but not uremic rats was stimulated by parathyroid hormone in a concentration-dependent fashion. However, no stimulation of guanylyl cyclase activity was noted by parathyroid hormone, although stimulation by sodium azide was present. Incubation of muscles with added parathyroid hormone produced a diminished responsiveness towards epinephrine or serotonin regulation of amino acid release and cAMP formation in the presence compared to the absence of parathyroid hormone. In the absence of parathyroid hormone, detectable inhibition of alanine and glutamine release was produced by 10(-9) M epinephrine, whereas in the presence of parathyroid hormone (1,000 ng/ml) inhibition of alanine and glutamine release required 10(-6) M or greater epinephrine. Resistance to cyclic AMP action as well as inhibition of cyclic AMP formation by parathyroid hormone was found. Preincubation of rat sarcolemma with 1-34 parathyroid hormone produced a decreased activity of the isoproterenol-stimulable adenylyl cyclase activity but there was no apparent change in the concentration of isoproterenol required for one-half maximal and maximal stimulation of the enzyme. These findings suggest that high levels of parathyroid hormone have direct effects on skeletal muscle protein, amino acid, and cyclic nucleotide metabolism in muscle of normal but not uremic animals. Treatment with these high levels of parathyroid hormone in vitro appears to reproduce in normal muscle, the metabolic deficits and loss of hormone responsiveness observed in muscle of chronically uremic animals. It is therefore possible that direct effects of parathyroid hormone on skeletal muscle may account in part for the muscle dysfunction and wasting of primary hyperparathyroidism and chronic uremia.
TL;DR: Ex vivo platelet aggregation in response to epinephrine was inhibited during yohimbine, showing that non-innervated alpha 2-adrenoreceptors were inhibited, and if yohimine is acting through blockade of alpha 2 receptors, then these receptors tonically suppress sympathetic outflow in humans.
Abstract: We studied the influence of the alpha 2-adrenoreceptor-blocking drug, yohimbine, on blood pressure, plasma norepinephrine, and other measures of autonomic function in normal male volunteers These studies were designed to evaluate the role of alpha 2-receptors in the tonic regulation of sympathetic outflow in humans In a dose-ranging study, we found that yohimbine HCl (0016-0125 mg/kg) elicited dose-related rises in mean, systolic, and diastolic pressures At the maximal dose used (0125 mg/kg), respective increments in mean, systolic, and diastolic pressures were 14 +/- 1 torr; 28 +/- 3 torr; and 8 +/- 1 torr (p less than 001) (mean +/- SE) No significant changes in heart rate occurred Associated with the rise in blood pressure were enhanced pressor and heart rate responses to the cold pressor, isometric handgrip, and Valsalva maneuvers In a double-blind study, yohimbine (0125 mg/kg bolus, 0001 mg/kg/min infusion) induced a two-to-threefold rise in plasma norepinephrine (p less than 001), without significantly altering plasma epinephrine or plasma renin activity Ex vivo platelet aggregation in response to epinephrine was inhibited during yohimbine, showing that non-innervated alpha 2-adrenoreceptors were inhibited Central effects of yohimbine were evaluated through use of linear analog mood rating scales which showed a shift from calm toward excited ends of these scales If yohimbine is acting through blockade of alpha 2 receptors, then these receptors tonically suppress sympathetic outflow in humans
TL;DR: It is demonstrated that chronic exposure to moderate and severe hypoxia increases the activity of the SNS and adrenal medulla, the effect being greater in severe hypoxic exposure.
Abstract: The sympathoadrenal responses to acute and chronic hypoxic exposure at 10.5 and 7.5% oxygen were determined in the rat. Cardiac norepinephrine (NE) turnover was used to assess sympathetic nervous system (SNS) activity, and urinary excretion of epinephrine (E) was measured as an index of adrenal medullary activity. The responses of the adrenal medulla and SNS were distinct and dependent upon the degree and duration of hypoxic exposure. Chronic hypoxia at 10.5% oxygen increased cardiac NE turnover by 130% after 3, 7, and 14 d of hypoxic exposure. Urinary excretion of NE was similarly increased over this time interval, while urinary E excretion was marginally elevated. In contrast, acute exposure to moderate hypoxia at 10.5% oxygen was not associated with an increase in SNS activity; in fact, decreased SNS activity was suggested by diminished cardiac NE turnover and urinary NE excretion over the first 12 h of hypoxic exposure, and by a rebound increase in NE turnover after reexposure to normal oxygen tension. Adrenal medullary activity, on the other hand, increased substantially during acute exposure to moderate hypoxia (2-fold increase in urinary E excretion) and severe hypoxia (greater than 10-fold). In distinction to the lack of effect of acute hypoxic exposure (10.5% oxygen), the SNS was markedly stimulated during the first day of hypoxia exposure at 7.5% oxygen, an increase that was sustained throughout at least 7 d at 7.5% oxygen. These results demonstrate that chronic exposure to moderate and severe hypoxia increases the activity of the SNS and adrenal medulla, the effect being greater in severe hypoxic exposure. The response to acute hypoxic exposure is more complicated; during the first 12 h of exposure at 10.5% oxygen, the SNS is not stimulated and appears to be restrained, while adrenal medullary activity is enhanced. Acute exposure to a more severe degree of hypoxia (7.5% oxygen), however, is associated with stimulation of both the SNS and adrenal medulla.
TL;DR: In a double-blind trial, the efficacy and safety of inhaled salbutamol (albuterol), nebulized with oxygen by face mask, and subcutaneous epinephrine in 40 children with acute asthma were compared.
TL;DR: Results on epinephrine plasma metabolic clearance rate agreed with earlier results in the literature and were in line with expectations.
Abstract: A test for determination of epinephrine sensitivity has been worked out using six healthy young women. Variables considered were metabolic rate, heart rate, respiratory frequency, blood pressure, blood glucose, plasma insulin, glycerol, free fatty acids, and lactate. After established basal conditions, epinephrine was infused at rates of 0.01, 0.03, and 0.1 microgram X kg fat-free mass-1 X min-1. Most variables responded to epinephrine in a dose-dependent manner. Physiological threshold plasma concentrations of epinephrine ranged from 95 to 250 pg/ml for different variables. Calculated maximal responses ranged from approximately -15% to +900% of basal values and infusion rates giving half-maximal responses from approximately 15 to 190 ng X kg fat-free mass-1 X min-1. On an average, metabolic rate increased by 8, 16, and 29%, respectively, at the three infusion rates, and the maximal metabolic response was calculated to be approximately 35%. The error in determining epinephrine-induced increments in metabolic rate was 7% of the response. As calculated from nonprotein RQ, carbohydrate oxidation increased and lipid oxidation decreased rapidly during the first 10 min of epinephrine infusion. Later, fat oxidation became more important. Results on epinephrine plasma metabolic clearance rate agreed with earlier results in the literature.
TL;DR: There is no significant hemodynamic response to lidocaine dental anesthesia (with or without epinephrine) in healthy young men.
Abstract: • To define the hemodynamic effects of local dental anesthesia, we measured the mean arterial pressure (MAP), heart rate, and plasma catecholamine responses for 60 minutes following an inferior alveolar nerve block with epinephrineand nonepinephrine-containing lidocaine hydrochloride anesthesia in 14 men using a randomized double-blind crossover trial. Lidocaine alone caused no significant change in MAP or heart rate and only slight, transient changes in plasma catecholamine concentrations when compared with baseline values. Lidocaine with epinephrine caused significant, sustained (60 minutes) increases in plasma epinephrine concentrations (mean±SEM, 27±4 to 94±13 pg/mL) and a slight, but transient (two-minute) increase in heart rate from 68±3 to 70±3 beats per minute. Lidocaine with epinephrine caused no significant change in MAP. There is no significant hemodynamic response to lidocaine dental anesthesia (with or without epinephrine) in healthy young men. ( Arch Intern Med 1983;143:2141-2143)
TL;DR: The four dexamethasone-resistant patients had significantly higher plasma norepinephrine and epinephrine levels than the five patients with normal suppression, suggesting greater sympathetic function in dex amethas one-resistant depressed patients.
Abstract: Of nine depressed patients given the dexamethasone suppression test, the four dexamethasone-resistant patients had significantly higher plasma norepinephrine and epinephrine levels than the five patients with normal suppression. These results suggest greater sympathetic function in dexamethasone-resistant depressed patients.
TL;DR: Evidence is provided that mu-opiate receptors primarily mediate cardiovascular effects of opiates in awake rats, at low doses, a sympathetic adrenomedullary activation occurs, whereas higher doses additionally activate parasympathetic efferents, both possibly from anterior hypothalamic sites.
Abstract: Intracerebroventricular injections of selective opioid agonists were used to investigate the role of opiate receptor subtypes in cardiovascular function in awake rats. The μ-agonist (D-Ala2,MePhe4,Gly5-ol)enkephalin (1 nmol) caused a prolonged increase in blood pressure and an initial decrease followed by a delayed increase in heart rate. These effects were antagonized by the selective μ-antagonist β-funaltrexamine. A selective 5-agonist (dimeric tetrapeptide enkephalin) was devoid of cardiovascular effects at 10 nmol, whereas a benzomorphan κ-agonist MRZ caused a pressor response which was not antagonized by β-funaltrexamine. The mechanisms by which opioids elicit cardiovascular effects were analyzed in detail by using microinjections into the anterior hypothalamic area. Low doses of enkephalin produced increases in heart rate and blood pressure. Associated elevations of plasma norepinephrine and epinephrine, but not vasopressin, suggested a stimulation of sympatho-adrenomedullary pathways. Higher doses ...
TL;DR: The efficacy of glucose counterregulation in a given patient may determine the degree to which euglycemia can be achieved with aggressive insulin therapy in that patient.
Abstract: Glucagon normally plays a primary role in promoting glucose recovery from insulin-induced hypoglycemia. Epinephrine compensates largely for deficient glucagon secretion. Glucose recovery from hypoglycemia fails to occur only in the absence of both glucagon and epinephrine. Perhaps as a relatively early feature of autonomic neuropathy, patients with insulin-dependent diabetes mellitus commonly have blunted or absent glucagon secretory responses to hypoglycemia. However, this deficient response is commonly compensated for by epinephrine and glucose recovery occurs. In some patients, progression of adrenergic neuropathy to the point of deficient epinephrine secretory responses to hypoglycemia, coupled with deficient glucagon responses, leads to frequent, severe, and prolonged hypoglycemia. Thus, these glucose counterregulatory systems are of critical importance to patients with insulindependent diabetes mellitus. The efficacy of glucose counterregulation in a given patient may determine the degree to which euglycemia can be achieved with aggressive insulin therapy in that patient.
TL;DR: It is concluded that at least some adrenal medulla grafts contain concentrations of dopamine sufficient to account for their behavioral effects.
TL;DR: Propranolol appears to be a useful antihypertensive drug in the hyperdynamic head-injured patient because it normalizes blood pressure and the underlying hemodynamic abnormalities both by its beta-adrenergic blocking action and by decreasing circulating levels of catecholamines.
Abstract: Arterial hypertension that occurs after severe head injury is characterized by elevation of systolic blood pressure, tachycardia, increased cardiac output, normal or decreased peripheral vascular resistance, and increased circulating catecholamines. The effects of two drugs used in the management of hypertension, propranolol and hydralazine, on these indices of cardiovascular function were examined in six head-injured patients. Both drugs effectively normalized blood pressure. However, hydralazine increased heart rate by 30%, cardiac index by 49%, left cardiac work by 21%, and pulmonary venous admixture by 53%, and was responsible for an increase in intracranial pressure or decreased compliance in two patients. Hydralazine produced no consistent change in arterial catecholamines. In contrast, propranolol decreased heart rate by 21%, cardiac index by 26%, left cardiac work by 35%, pulmonary venous admixture by 15%, and oxygen consumption by 18%. Propranolol decreased arterial epinephrine levels by 48% and norepinephrine levels by 28%. Propranolol appears to be a useful antihypertensive drug in the hyperdynamic head-injured patient because it normalizes blood pressure and the underlying hemodynamic abnormalities both by its beta-adrenergic blocking action and by decreasing circulating levels of catecholamines.
TL;DR: The results indicate that different tissues and different adrenergic receptor subtypes may have varying susceptibility to down-regulation in response to increased circulating catecholamines in vivo.
Abstract: We have used an animal model of pheochromocytoma and radioligand-binding techniques to examine the effects of high levels of circulating norepinephrine and dopamine on adrenergic receptor subtypes in several peripheral tissues. New England Deaconess Hospital rats with transplanted pheochromocytomas were hypertensive and had levels of plasma norepinephrine and dopamine 50-fold greater than those of controls. The number of beta-adrenergic receptors in membranes prepared from the renal cortex and the left ventricle from these rats was decreased about 50%, but the animals had no significant decrease in the overall number of beta-adrenergic receptors in pulmonary membranes. beta-Receptor affinity was unaltered in animals with pheochromocytoma. Competition for [125I]iodocyanopindolol binding to beta-receptors by subtype-selective agents indicated a selective decrease of about 80% in the number of beta 1-adrenergic receptors in renal cortical and pulmonary membranes, without a decrease in beta 2-adrenergic receptor number. Rats with pheochromocytoma also had about a 70% decrease in the number of alpha 1-adrenergic receptors in membranes from renal cortex and lung, but no significant decrease in the number of alpha 1-adrenergic receptors in hepatic membranes and no decrease in the number of alpha 2-adrenergic receptors in renal cortical and hepatic membranes. These results indicate that rats in which pheochromocytomas are transplanted show adrenergic receptor subtype- and tissue-specific down-regulation. Although the selective down-regulation of alpha 1- and beta 1-adrenergic receptors may reflect a response to the preponderance of norepinephrine in these animals, the results indicate that different tissues and different adrenergic receptor subtypes may have varying susceptibility to down-regulation in response to increased circulating catecholamines in vivo.
TL;DR: The data indicate that epinephrine in physiologic concentrations is a hypophosphatemic hormone in man, and it is suggested that it is a direct effect of epinphrine, in that it was not mediated by changes in availability of the primary regulatory hormones PTH and CT, although indirect effects mediated byChanges in other hormones, such as insulin, cannot be excluded.
Abstract: The physiologic effects of epinephrine on mineral metabolism are not known. In six healthy men, insulin-induced hypoglycemia, a potent stimulus to endogenous epinephrine secretion, resulted in a decrement of 0.9±0.1 mg/dl (mean±SE, P < 0.001) in serum inorganic phosphorus and smaller increments in magnesium and total and ionized calcium. Plasma immunoreactive parathyroid hormone (iPTH) decreased and plasma immunoreactive calcitonin (iCT) increased appropriately with the increments in calcium and magnesium. We wished to determine to what extent these changes in mineral metabolism might be attributable to epinephrine. Therefore, in the same protocol, we infused the hormone over 60 min in these six men, in doses that resulted in steady-state plasma epinephrine concentrations ranging from 52 to 945 pg/ml (levels that span the physiologic range), for a total of 25 studies. Serum ionized calcium, iPTH, and iCT concentrations were unaltered by these physiologic elevations of plasma epinephrine. However, epinephrine resulted in dose-dependent decrements in serum inorganic phosphorus of 0.6±0.1 mg/dl (P < 0.005) for the highest epinephrine infusion rate. The plasma epinephrine concentration threshold for this hypophosphatemic effect was ∼50-100 pg/ml. Thus, the sensitivity of the hypophosphatemic response to epinephrine is comparable to that of the cardiac chronotropic, systolic pressor, and lipolytic responses to epinephrine, and considerably greater than that of the diastolic depressor, glycogenolytic, glycolytic, and ketogenic responses to the hormone in human beings. In view of its rapidity, the hypophosphatemic effect of epinephrine is probably the result of a net shift of phosphate from the extracellular compartment to intracellular compartments. We suggest that it is a direct effect of epinephrine, in that it is not mediated by changes in availability of the primary regulatory hormones PTH and CT, although indirect effects mediated by changes in other hormones, such as insulin, cannot be excluded. The hypophosphatemic response is also not attributable to increments in plasma calcium. These data indicate that epinephrine in physiologic concentrations is a hypophosphatemic hormone in man.
TL;DR: The present data show that the additive effect of epinephrine on CRF-induced ACTH release is achieved through an alpha-adrenergic receptor and is accompanied by a marked stimulation of intracellular cyclic AMP levels.
TL;DR: It is suggested that an opioid-mediated amnesic mechanism modulates the effect of ACTH and epinephrine on memory consolidation, either by dampening that effect when training parameters tend to make it facilitatory, or by enhancing it when training conditions tend to making it amnesics.
TL;DR: It is suggested that the POM, a central nucleus in the AV3V region, may be an important forebrain site for autonomic regulation by TRH, mediated through the sympathetic nervous system.
TL;DR: The findings suggest that the integrity of the ST, which connects the amygdala and other brain structures, is essential for the effect of epinephrine on memory processes and the possible involvement of the brain structures processing visceral information in the memory modulatory effect ofEpinephrine is discussed.
TL;DR: Postsynaptic myocardial α1 adrenergic receptors mediate most of the sensitization by halothane to the ventricular arrhythmogenic effects of catecholamines, while a lesser contribution is conferred by the β1 adrenoceptors.
Abstract: The adrenergic receptor mechanism by which halothane sensitizes the myocardium to the ventricular arrhythmogenic properties of catecholamines is unknown. The new generation of selective adrenergic receptor antagonists have been used to determine which receptor blockade causes the greater increase in the dose of epinephrine needed to achieve a threshold for ventricular arrhythmias. Dogs anesthetized with 1.2 MAC halothane had an arrhythmogenic dose of epinephrine (ADE) of 2.2 micrograms X kg X min-1 that significantly increased (P less than 0.01) to 27 micrograms X kg-1 X min-1 after alpha 1 blockade with prazosin. beta 1 blockade with metoprolol also significantly increased the ADE to 12 micrograms X kg-1 X min-1 (P less than 0.05) but was less than the effect noted after prazosin treatment (P less than 0.05). The dramatic increase in the threshold for arrhythmias noted after prazosin could not be ascribed solely to its hemodynamic properties because treatment with sodium nitroprusside did not change the ADE (2.7 micrograms X kg-1 X min-1) significantly; yet nitroprusside treatment resulted in a similar drop in mean arterial pressure (59 mmHg) to that of prazosin treatment (51 mmHg) when compared with the control group. Thus postsynaptic myocardial alpha 1 adrenergic receptors mediate most of the sensitization by halothane to the ventricular arrhythmogenic effects of catecholamines, while a lesser contribution is conferred by the beta 1 adrenoceptors. These results have implications for the treatment and identification of patients particularly at risk from halothane-epinephrine interactions.
TL;DR: It is suggested that casein kinase-I and/or casein Kinase-II may mediate the insulin-stimulated phosphorylation of acetyl-CoA carboxylase to account for the expected epinephrine-induced activation of the cAMP-dependent protein kinase.
TL;DR: The transition from exogenous glucose delivery to endogenous glucose production late after glucose ingestion is the result of the coordinated diminution of insulin secretion and the resumption of glucagon secretion, and enhanced epinephrine secretion compensates largely and prevents hypoglycemia when glucagon gland is deficient.
Abstract: The transition from exogenous glucose delivery to endogenous glucose production late after glucose ingestion is not solely attributable to dissipation of insulin and, therefore, must also involve factors that actively raise the plasma glucose concentration--glucose counterregulatory factors. We have shown that the secretion of two of these, glucagon and epinephrine, is specific for glucose ingestion and temporally related to the glucose counterregulatory process. To determine the physiologic roles of glucagon and epinephrine in postprandial glucose counterregulation, we produced pharmacologic interventions that resulted in endogenous glucagon deficiency with and without exogenous glucagon replacement, adrenergic blockade, and adrenergic blockade coupled with glucagon deficiency starting 225 min after the ingestion of 75 g of glucose in normal subjects. Also, we assessed the effect of endogenous epinephrine deficiency alone and in combination with glucagon deficiency late after glucose ingestion in bilaterally adrenalectomized subjects. Glucagon deficiency resulted in nadir plasma glucose concentrations that were approximately 30% lower (P less than 0.01) than control values, but did not cause hypoglycemia late after glucose ingestion. This effect was prevented by glucagon replacement. Neither adrenergic blockade nor epinephrine deficiency alone impaired the glucose counterregulatory process. However, combined glucagon and epinephrine deficiencies resulted in a progressive fall in mean plasma glucose to a hypoglycemic level late after glucose ingestion; the final glucose concentration was 40% lower (P less than 0.02) than the control (epinephrine deficient) value in these patients, and was nearly 50% lower (P less than 0.001) than the control value and approximately 30% lower (P less than 0.05) than the glucagon-deficient value in normal subjects. We conclude (a) the transition from exogenous glucose delivery to endogenous glucose production late after glucose ingestion is the result of the coordinated diminution of insulin secretion and the resumption of glucagon secretion. (b) Epinephrine does not normally play a critical role in this process, but enhanced epinephrine secretion compensates largely and prevents hypoglycemia when glucagon secretion is deficient.