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Showing papers on "Epinephrine published in 1984"


Journal ArticleDOI
TL;DR: The hypothesis was that epinephrine would improve myocardial and cerebral blood flow by preventing collapse of intrathoracic arteries and by vasoconstricting other vascular beds, thereby increasing perfusion pressures and improving electroencephalographic activity and restoration of spontaneous circulation.
Abstract: The goals of this study were to quantify the effects of epinephrine on myocardial and cerebral blood flow during conventional cardiopulmonary resuscitation (CPR) and CPR with simultaneous chest compression-ventilation and to test the hypothesis that epinephrine would improve myocardial and cerebral blood flow by preventing collapse of intrathoracic arteries and by vasoconstricting other vascular beds, thereby increasing perfusion pressures. Cerebral and myocardial blood flow were measured by the radiolabeled microsphere technique, which we have previously validated during CPR. We studied the effect of epinephrine on established arterial collapse during CPR with simultaneous chest compression-ventilation with the abdomen bound or unbound. Epinephrine reversed arterial collapse, thereby eliminating the systolic gradient between aortic and carotid pressures and increasing cerebral perfusion pressure and cerebral blood flow while decreasing blood flow to other cephalic tissues. Epinephrine produced higher cerebral and myocardial perfusion pressures during CPR with simultaneous chest compression-ventilation when the abdomen was unbound rather than bound because abdominal binding increased intracranial and venous pressures. In other experiments we compared the effect of epinephrine on blood flow during 1 hr of either conventional CPR or with simultaneous chest compression-ventilation with the abdomen unbound. Epinephrine infusion during conventional CPR produced an average cerebral blood flow of 15 ml/min . 100 g (41 +/- 15% of control) and an average myocardial blood flow of 18 ml/min . 100 g (15 +/- 8% of control). In our previous studies, cerebral and myocardial blood flow were less than 3 +/- 1% of control during conventional CPR without epinephrine. Although flows during CPR with simultaneous chest compression-ventilation without epinephrine were initially higher than those during conventional CPR, arterial collapse developed after 20 min, limiting cerebral and myocardial blood flow. The use of epinephrine throughout 50 min of CPR with simultaneous chest compression-ventilation maintained cerebral blood flow at 22 +/- 2 ml/min . 100 g (73 +/- 25% control) and left ventricular blood flow at 38 +/- 9 ml/min . 100 g (28 +/- 8% control). The improved blood flows with epinephrine correlated with improved electroencephalographic activity and restoration of spontaneous circulation.(ABSTRACT TRUNCATED AT 400 WORDS)

439 citations


Journal ArticleDOI
TL;DR: Triple hormone infusion simulated many of the metabolic responses observed following mild-moderate injury and other catabolic illnesses, and indicated that these responses resulted from both additive and synergistic interactions of the hormones.
Abstract: To investigate the role of hormones as mediators of the metabolic response to injury, nine normal male volunteers received a continuous 74-hour infusion of the three 'stress' hormones: cortisol, glucagon, and epinephrine. As a control, each subject received a saline infusion during another 4-day period. Diets were constant and matched on both occasions. Hormonal infusion achieved hormone concentrations similar to those seen following mild-moderate injury. With this alteration in the endocrine environment significant hypermetabolism, negative nitrogen and potassium balances, glucose intolerance, hyperinsulinemia, insulin resistance, sodium retention, and peripheral leukocytosis were observed. Additional studies with single hormone infusions indicated that these responses resulted from both additive and synergistic interactions of the hormones. Triple hormone infusion simulated many of the metabolic responses observed following mild-moderate injury and other catabolic illnesses.

403 citations


Journal ArticleDOI
TL;DR: The physiological contribution of the adrenal medulla would be particularly important under conditions of SNS suppression, as well as for certain stimuli the SNS response is biphasic, with an initial suppression followed by subsequent stimulation.
Abstract: The relative importance of sympathetic nerve (SNS) activity and adrenal medullary secretion in various physiological situations has generally been inferred from measurements of norepinephrine (NE) and epinephrine (E), respectively, in urine or plasma. Increasing evidence, however, indicates that under certain conditions the adrenal medulla may release substantial amounts of NE as well as E. In several of these circumstances, estimates of SNS activity based on the measurement of NE turnover in peripheral tissues of experimental animals indicate diminished SNS function, a reduction that is independent of adrenal medullary secretion. These reciprocal alterations in SNS and adrenal medullary activity fall into two patterns. First, when SNS activity is suppressed by fasting, adrenal medullary responses to various stimuli are enhanced. Second, for certain stimuli the SNS response is biphasic, with an initial suppression followed by subsequent stimulation; during the first phase adrenal medullary secretion is markedly increased. The physiological contribution of the adrenal medulla, therefore, would be particularly important under conditions of SNS suppression.

216 citations


Journal ArticleDOI
TL;DR: It is concluded that chronic, severe stress produces only moderate elevations of plasma epinephrine levels, whereas acute stress produces marked increases of plasmaEpinephrine that may reach the extraordinarily high level of 35.9 ng/ml, and under close medical monitoring, it is possible to survive with plasma Epinephrine concentrations as high as 273 ng/ML.

188 citations


Journal ArticleDOI
01 Oct 1984-Gut
TL;DR: Increased arterial noradrenaline in decompensated and recompensated cirrhosis is only to a limited extent owing to reduced net splanchnic elimination of catecholamines in cirrhoses, indicating enhanced sympathetic nervous tone in these conditions.
Abstract: Plasma noradrenaline (NA) and adrenaline (A) concentrations were determined in different vascular areas in 32 patients with cirrhosis and in nine controls during a right sided heart, liver, and renal vein catheterisation. The patients were divided into four groups: (I) Compensated (without ascites); (II) Recompensated on diuretic treatment because of former ascites; (III) Decompensated (with ascites) without treatment and (IV) Decompensated on diuretic treatment. Median arterial noradrenaline concentrations were 1.48, 1.07, 2.66, 4.14 and 2.50 nmol/l in controls, group I, II, III, and IV, respectively, the three last mentioned values being significantly raised (p less than 0.01). Median arterial adrenaline concentrations were not significantly increased. In patients arterial-hepatic venous extraction ratios of noradrenaline and adrenaline were on the average 25% (p less than 0.01) and 20% (p less than 0.02) less than those of the controls, indicating a slightly reduced splanchnic elimination of catecholamines in cirrhoses. In controls and group I significant renal venous-arterial noradrenaline differences were absent (0.00 and 0.03 nmol/l) while renal venous-arterial noradrenaline differences were significantly increased in groups II, III and IV (0.47, 0.53 and 0.68 nmol/l, p less than 0.01), indicating a significant net release of noradrenaline from the kidneys in recompensated and decompensated patients. Renal extraction of adrenaline was normal. In conclusion, increased arterial noradrenaline in decompensated and recompensated cirrhosis is only to a limited extent owing to reduced net splanchnic elimination. More likely the increase is caused by release of noradrenaline from the kidneys and possibly other organs indicating enhanced sympathetic nervous tone in these conditions.

178 citations


Journal ArticleDOI
TL;DR: The above findings suggest that patients with migraine show sympathetic hypofunction together with denervation hypersensitivity of the iris and the arteries, and that a defective noradrenergic nervous system may play a role in the pathogenesis of migraine.
Abstract: • The autonomic nervous function in patients with migraine was studied during headache-free intervals. The following observations were made: (1) a decrease in overshoot in Valsalva's maneuver; (2) orthostatic hypotension; (3) low levels of plasma norepinephrine in the steady state; (4) failure in elevation of the plasma norepinephrine level after head-up tilting; (5) dilatation of the pupils after instillation in the eye of 1.25% epinephrine; and (6) a long recovery time in tests by bolus injection of 0.1 μg of norepinephrine bitartrate per kilogram. The above findings suggest that patients with migraine show sympathetic hypofunction together with denervation hypersensitivity of the iris and the arteries, and that a defective noradrenergic nervous system may play a role in the pathogenesis of migraine.

158 citations


Journal ArticleDOI
01 Jan 1984-Drugs
TL;DR: The effects of catecholamines in the central and peripheral nervous systems appear to be mediated through interactions with two major classes of receptor: α-adrenoceptors and β-adsensors as mentioned in this paper.
Abstract: The effects of catecholamines in the central and peripheral nervous systems appear to be mediated through interactions with 2 major classes of receptor: α-adrenoceptors and β-adrenoceptors. Subtypes of both α- and β-adrenoceptors exist. In the periphery, α1-receptors are located postsynaptically, mediating the excitatory effects of catecholamines at α-receptors. α2-Adrenoceptors, on the other hand, are autoreceptors involved in the regulation of noradrenaline (norepinephrine) release. In the central nervous system, both α1- and α2-receptors exist on postsynaptic cells; there are also 2 principal subtypes of β-adrenoceptors. β1-Receptors have a high affinity for both noradrenaline and adrenaline (epinephrine) and are found in the heart, brain, and adipose tissue. β2-Receptors have a low affinity for noradrenaline and are involved in mediation of relaxation of vascular and other smooth muscles and in many of the metabolic effects of catecholamines.

158 citations


Journal ArticleDOI
TL;DR: The secretion of adrenal medullary hormones can be controlled reflexly by mechanical cutaneous stimulation through the central nervous system via adrenal sympathetic efferent nerves via cutaneous mechanical stimulation.

149 citations


Journal ArticleDOI
TL;DR: Results in the chronically instrumented fetal lamb suggest that changes in the ST waveform expressed as T/QRS ratio identify a change to anaerobic myocardial metabolism mediated by beta-adrenergic stimulation.

129 citations


Journal ArticleDOI
TL;DR: Plasma epinephrine and norepinephrine rose sharply within 30 minutes of the seizure and then declined rapidly, and was attributed to generalized sympathetic neural activation and was sufficient to exert a direct vasoconstrictor effect.
Abstract: Concentrations of circulating catecholamines increase after induced seizures in animals and electroconvulsive therapy in humans. We measured plasma epinephrine and norepinephrine concentrations after a single spontaneous tonic-clonic convulsion in 17 patients to determine whether similar changes occur and to determine their magnitude. Plasma epinephrine and norepinephrine rose sharply within 30 minutes of the seizure and then declined rapidly. The norepinephrine response was attributed to generalized sympathetic neural activation and was sufficient to exert a direct vasoconstrictor effect. The epinephrine response was presumably due to adrenal activation and was large-enough to have cardiovascular or metabolic consequences.

121 citations


Journal ArticleDOI
TL;DR: The findings suggest that epinephrine is an important contributor to stress-induced hyperglycemia and the susceptibility of diabetics to the adverse metabolic effects of stress.
Abstract: Epinephrine causes a prompt increase in blood glucose concentration in the postabsorptive state. This effect is mediated by a transient increase in hepatic glucose production and an inhibition of glucose disposal by insulin-dependent tissues. Epinephrine augments hepatic glucose production by stimulating glycogenolysis and gluconeogenesis. Although its effect on glycogenolysis rapidly wanes, hyperglycemia continues because the effects of epinephrine on gluconeogenesis and glucose disposal persist. Epinephrine-induced hyperglycemia is markedly accentuated by concomitant elevations of glucagon and cortisol or in patients with diabetes. In both cases, the effect of epinephrine on hepatic glucose production is converted from a transient to a sustained response, thereby accounting for the exaggerated hyperglycemia. During glucose feeding, mild elevations of epinephrine that have little effect on fasting glucose levels cause marked glucose intolerance. This exquisite sensitivity to the diabetogenic effects of epinephrine is accounted for by its capacity to interfere with each of the components of the glucoregulatory response, i.e., stimulation of splanchnic and peripheral glucose uptake and suppression of hepatic glucose production. Our findings suggest that epinephrine is an important contributor to stress-induced hyperglycemia and the susceptibility of diabetics to the adverse metabolic effects of stress.

Journal ArticleDOI
TL;DR: It is concluded that serum Na concentration serves as a useful index of activation of the sympathetic nervous system, renin-angiotensin system, and impairment of regional perfusion in patients with advanced CHF.
Abstract: To study the relationship between serum Na concentration and impairment of homeostatic mechanisms in advanced congestive heart failure (CHF), we evaluated the status of the sympathetic nervous system, renin-angiotensin system, and regional visceral blood flow in 26 patients with this syndrome. Compared with normal subjects, hyponatremic patients had marked stimulation of PRA (P = 0.012), norepinephrine (P less than 0.001), and epinephrine (P less than 0.001) with severe impairment of renal (P less than 0.001) and hepatic (P less than 0.003) plasma flows. In contrast, normonatremic patients, with an apparently similar degree of CHF, demonstrated less pronounced abnormalities in all of these parameters. Moreover, the responses of neurohormones and regional blood flow to orthostatic stress were greatly attenuated in the hyponatremic patients, whereas, the normonatremic subjects had more normal responses. We conclude that serum Na concentration serves as a useful index of activation of the sympathetic nervous system, renin-angiotensin system, and impairment of regional perfusion in patients with advanced CHF.

Journal ArticleDOI
TL;DR: It is suggested that epinephrine inhibits insulin release at a step distal to the generation of cyclic AMP.

Journal ArticleDOI
TL;DR: Results indicate that intraoral injections of epinephrine-containing local anesthetics result in increased circulating epinphrine levels that are associated with cardiovascular changes and that diazepam premedication decreases plasma norepinephrine levels and attenuates the sympathoadrenal response to surgical stress.
Abstract: The effects of diazepam premedication and administration of an epinephrine-containing local anesthetic on plasma catecholamine levels and cardiovascular parameters were evaluated prior to and during a minor surgical procedure, the removal of impacted third molars. Significant elevations in circulating epinephrine levels (203% above control) and cardiac output (30%) were seen in unsedated patients after administration of lidocaine with epinephrine before surgery, while no changes were seen after lidocaine alone. Unsedated patients had increased norepinephrine (24%) and epinephrine (57%) levels during surgery. Diazepam premedication decreased norepinephrine levels 29% below preoperative levels, followed by an increase during surgery to preoperative levels. These results indicate that intraoral injections of epinephrine-containing local anesthetics result in increased circulating epinephrine levels that are associated with cardiovascular changes and that diazepam premedication decreases plasma norepinephrine levels and attenuates the sympathoadrenal response to surgical stress.

Journal ArticleDOI
TL;DR: There was a strong relationship between the circadian changes in plasma dopamine levels and those of norepinephrine and epinephrine throughout the 24-h period of recumbency, consistent with a common regulatory mechanism governing the sleep/wake and/or rest/activity in plasma catecholamine levels.
Abstract: Nocturnal and daytime recumbent secretory patterns of norepinephrine, epinephrine and dopamine were determined at 30 min intervals in 9 normotensive males. Plasma levels of dopamine as well as those of norepinephrine and epinephrine followed a circadian pattern in these recumbent males. Plasma levels of dopamine were more closely related to clock time (r = -0.54, p < 0.001) than either norepinephrine or epinephrine levels. As for norepinephrine and epinephrine, the sleep period in all 9 males was characterized by a paucity of dopamine secretory peaks as well as lower mean dopamine levels than during the awake state. There was a strong relationship between the circadian changes in plasma dopamine levels and those of norepinephrine ( r = 0.92) and epinephrine (r = 0.78) throughout the 24-h period of recumbency. These interrelationships are consistent with a common regulatory mechanism governing the sleep/wake and/or rest/activity in plasma catecholamine levels.

Journal ArticleDOI
TL;DR: Results indicate the presence of a beta 1-adrenergic receptor stimulating aldosterone secretion in bovine zona glomerulosa cells, suggesting a potential role of cAMP as a mediator of isoproterenol stimulation.
Abstract: Primary culture of bovine adrenal subcapsular cells was used to investigate direct effects of catecholamines on aldosterone secretion. Cells dispersed with collagenase and DNAse and cultured at high density (1.5–2 million/ml) for 3 days displayed high sensitivity to angiotensin II and ACTH, with an ED60 of 1.4 and 1.5 nm, respectively. Adrenergic agonists elicited a 4- to 6-fold stimulation of aldosterone secretion with potency order (−)isoproterenol greater than (−)epinephrine equals (−)norepinephrine greater than (+)isoproterenol, and corresponding ED50 5, 240, 213, and 3000 nm, respectively. No reproducible inhibition by dopamine of basal or stimulated levels of aldosterone secretion could be detected, but a weak stimulatory effect was sometimes observed at high concentration greater than 10 μM. (−)Isoproterenol stimulation of aldosterone production was potently inhibited by the β-adrenergic antagonists (−)alprenolol and (+)alprenolol with potencies of 1.8 and 110 nm, respectively. The α-adrenergic ant...

Journal ArticleDOI
TL;DR: The studies described in this paper support the hypothesis that specific brain peptides may act as neurochemical substrates for the differential patterns of sympathetic nervous system and adrenomedullary responses to various provocative stimuli.
Abstract: The studies described in this paper support the hypothesis that specific brain peptides may act as neurochemical substrates for the differential patterns of sympathetic nervous system and adrenomedullary responses to various provocative stimuli. Different treatments, e.g., exposure to ether vapor or cold, hemorrhage or hypoglycemia, elicit stimulus-specific changes in plasma concentrations of epinephrine and norepinephrine. Likewise, several neuropeptides, e.g., bombesin, corticotropin-releasing factor, thyrotropin-releasing factor, and somatostatin-related peptides, act within the central nervous system to produce differential changes in the relative concentrations of epinephrine and norepinephrine in plasma. The possibility that these peptides may be involved in generating stimulus-specific changes in plasma catecholamine concentrations following various physiological and pharmacological treatments is discussed.

Journal ArticleDOI
TL;DR: In six normal supine subjects epinephrine infusion produced a greater leukocytosis with smaller changes in heart rate and blood pressure than did norepinephrine or isoproterenol, which suggests that increased perfusion of low-flow areas in the lung may contribute to the increased leukocytes seen in association with both exercise and catecholamine infusion.
Abstract: In six normal supine subjects epinephrine infusion produced a greater leukocytosis with smaller changes in heart rate and blood pressure than did norepinephrine or isoproterenol. Upright exercise i...

Journal Article
TL;DR: The Schild plot data for lCl 118,551 ( beta-2 selective) indicated that the minor population (beta-1) was less important in aorta than in pulmonary artery, and the negative log EC50 of fenoterol, but not of isoproterenol or norepinephrine, was less than in preparations from young rats, which could indicate that aging had affected Beta-2 more than beta-1 adrenoceptor-mediated responses.
Abstract: Rat pulmonary artery contains both alpha adrenoceptors mediating contraction and beta-1 and beta-2 adrenoceptors mediating relaxation. Neither alpha nor beta adrenoceptor-mediated responses of this vessel to norepinephrine or epinephrine were potentiated by cocaine, despite evidence for the presence of some adrenergic nerves. Beta adrenoceptor-mediated relaxation of pulmonary artery, but not aorta, modulated alpha adrenoceptor-mediated contractions to epinephrine but not norepinephrine. Rat aorta also contains both beta-1 and beta-2 adrenoceptors mediating relaxation, in that Schild plots for atenolol (beta-1 selective antagonist) using a beta-1 selective agonist (norepinephrine) and a beta-2 selective agonist (fenoterol), respectively, were not superimposed. The Schild plot data for lCl 118,551 (beta-2 selective) indicated that the minor population (beta-1) was less important in aorta than in pulmonary artery. On preparations from 18-month-old rats, the maximum relaxation to isoproterenol (20.4%, aorta and 67.9%, pulmonary artery) was less than in preparations from young rats (79.8%, aorta and 96.9%, pulmonary artery), i.e., aging had reduced the beta adrenoceptor-mediated relaxation in both vessels, but particularly in aorta. Also, the negative log EC50 of fenoterol, but not of isoproterenol or norepinephrine, was less than in preparations from young rats. This could indicate that aging had affected beta-2 more than beta-1 adrenoceptor-mediated responses and may explain why aging depressed the maximum relaxation of aorta more than that of pulmonary artery.

Journal ArticleDOI
TL;DR: Because phenylephrine and methoxamine do not have significant beta-adrenergic actions, they should be considered as alternatives to epinephrine for aid in restoring spontaneous circulation.

Journal ArticleDOI
TL;DR: It was concluded that intravenous urographic contrast medium may elevate plasma catecholamines in a significant proportion of patients with pheochromocytoma, but that with adequate alpha adrenergic blockade this should pose no threat.
Abstract: Hypertensive crises have been provoked in pheochromocytoma patients by the injection of contrast media during angiography and venography. Fear of similar reactions to intravenous urographic contrast medium injection during computed tomography has led to studies without contrast enhancement when pheochromocytoma is suspected. With extraadrenal pheochromocytomas, intravenous contrast enhancement may be essential for tumor location by computed tomography. The catecholamine responses to injection of urographic contrast medium were examined in eight patients with pheochromocytoma and in 12 undergoing computed tomography for other reasons. Plasma norepinephrine concentrations fell in nonpheochromocytoma patients (p less than 0.005), while in pheochromocytoma patients the response was unpredictable, rising in six individuals, although the mean response was not significant (p greater than 0.35). In five patients the magnitude of the increase in norepinephrine concentrations was large enough to have led to a pressor effect had alpha adrenergic blockade not been used. It was concluded that intravenous urographic contrast medium may elevate plasma catecholamines in a significant proportion of patients with pheochromocytoma, but that with adequate alpha adrenergic blockade this should pose no threat.

Journal ArticleDOI
TL;DR: Among the groups receiving epinephrine, however, there was no difference in the absolute ADP and diastolic coronary perfusion pressure, and the drop in ADP over time noted in the control group was prevented by increasing doses ofEpinephrine.

Journal ArticleDOI
TL;DR: The results show that both vasoconstrictor agents in the doses used significantly prolong duration of sensory anesthesia and motor blockade produced by the subarachnoid administration of tetracaine.
Abstract: A randomized double-blind study was conducted in 50 orthopedic patients to determine the effect of epinephrine and phenylephrine on the anesthetic properties of intrathecally administered tetracaine. Two doses of each vasoconstrictor agent were studied: 0.2 mg of epinephrine, 0.3 mg of epinephrine, 1 mg of phenylephrine, and 2 mg of phenylephrine. The results show that both vasoconstrictor agents in the doses used significantly prolong duration of sensory anesthesia and motor blockade produced by the subarachnoid administration of tetracaine. At equipotent doses no differences existed between the ability of epinephrine and phenylephrine to prolong the duration of spinal anesthesia produced by tetracaine.

Journal ArticleDOI
TL;DR: It is concluded that the glucose homeostatic response to exercise in insulin-dependent diabetics, in contrast to healthy controls, is critically dependent on the adrenergic nervous system.
Abstract: We investigated the effects of alpha and/or beta adrenergic blockade (with phentolamine and/or propranolol) on glucose homeostasis during exercise in six normal subjects and in seven Type I diabetic subjects The diabetics received a low dose insulin infusion (007 mU/kg X min) designed to maintain plasma glucose at approximately 150 mg/dl In normals, neither alpha, beta, nor combined alpha and beta adrenergic blockade altered glucose production, glucose uptake, or plasma glucose concentration during exercise In diabetics, exercise alone produced a decline in glucose concentration from 144 to 116 mg/dl This was due to a slightly diminished rise in hepatic glucose production in association with a normal increase in glucose uptake When exercise was performed during beta adrenergic blockade, the decline in plasma glucose was accentuated An exogenous glucose infusion (258 mg/kg X min) was required to prevent glucose levels from falling below 90 mg/dl The effect of beta blockade was accounted for by a blunted rise in hepatic glucose production and an augmented rise in glucose utilization These alterations were unrelated to changes in plasma insulin and glucagon levels, which were similar in the presence and absence of propranolol In contrast, when the diabetics exercised during alpha adrenergic blockade, plasma glucose concentration rose from 150 to 164 mg/dl This was due to a significant increase in hepatic glucose production and a small decline in exercise-induced glucose utilization These alterations also could not be explained by differences in insulin and glucagon levels We conclude that the glucose homeostatic response to exercise in insulin-dependent diabetics, in contrast to healthy controls, is critically dependent on the adrenergic nervous system

Journal ArticleDOI
TL;DR: It is proposed that extra-CNS catecholamine-producing tissues be termed the sympathochromaffin system consisting of two components: 1) the sympathetic nervous system that releases the neurotransmitter norepinephrine from its postganglionic neurons, and 2) the chromaffin tissues that contain cells that secrete epinephrine, norpinephrine, or dopamine.
Abstract: Hypoglycemia stimulates adrenomedullary epinephrine secretion; standing stimulates sympathetic neural norepinephrine release. In five bilaterally adrenalectomized persons plasma epinephrine, measured with a sensitive single-isotope derivative assay, rose from 15 +/- 2 to 35 +/- 7 pg/ml (P less than 0.02) during hypoglycemia but did not increase during standing. In contrast, plasma norepinephrine rose during standing but not during hypoglycemia. Thus, in humans 1) extra-adrenal epinephrine secretion is regulated and derived from innervated cells other than sympathetic postganglionic neurons; 2) because the plasma levels of epinephrine in adrenalectomized individuals even in response to the potent stimulus of hypoglycemia are below physiological thresholds, any biological actions of extra-adrenal epinephrine in adults must be paracrine rather than endocrine in nature; 3) hypoglycemia does not appear to stimulate the sympathetic nervous system. In view of these findings, we propose that extra-CNS catecholamine-producing tissues be termed the sympathochromaffin system consisting of two components: 1) the sympathetic nervous system that releases the neurotransmitter norepinephrine from its postganglionic neurons, and 2) the chromaffin tissues, including the adrenal medullae, that contain cells that secrete epinephrine, norepinephrine, or dopamine. The plasma epinephrine concentration is a valid measure of its chromaffin tissue (predominantly adrenomedullary) secretion, whereas the plasma norepinephrine concentration is an index of sympathetic neuronal activity under some but not all conditions.

Journal ArticleDOI
TL;DR: Oral administration of the relatively selective β1-adrenergic antagonist metoprolol and of the nonselective β-adRenergic antagonist propranolol both impaired recovery from insulin-induced hypoglycemia in patients with IDDM.
Abstract: To the extent that they have deficient glucagon secretory responses to plasma glucose decrements, as they commonly do, patients with insulin-dependent diabetes mellitus (IDDM) are dependent on epinephrine-mediated beta-adrenergic mechanisms to promote recovery from hypoglycemia. Thus, they are at increased risk for prolonged hypoglycemia if treated with a nonselective beta-adrenergic antagonist such as propranolol. If the hyperglycemic actions of epinephrine are mediated through beta 2-adrenergic mechanisms, therapeutic efficacy (e.g., for hypertension or ischemic heart disease) could be accomplished without increased risk of hypoglycemia by selective beta 1-adrenergic blockade in such patients. However, oral administration of the relatively selective beta 1-adrenergic antagonist metoprolol (100 mg) and of the nonselective beta-adrenergic antagonist propranolol (80 mg) both impaired recovery from insulin-induced hypoglycemia in patients with IDDM. Thus, at a dose of 100 mg, oral metoprolol is not safer than oral propranolol with respect to recovery from hypoglycemia in patients with IDDM.

Journal ArticleDOI
TL;DR: It is concluded that vasomotor syncope occurs quite frequently in patients with severe chronic heart failure after captopril in a small dose and is associated with a selective increase in epinephrine secretion from the adrenal medulla.

Journal ArticleDOI
TL;DR: The results show that morphine-induced hyperglycemia results from both stimulation of glucose production as well as inhibition of glucose clearance, and is postulate that the hypoglycemic effect of morphine results from the interaction of the opiate with non-mu receptors either in the liver or the central nervous system.
Abstract: This study was designed to assess the effects of morphine sulfate on glucose kinetics and on glucoregulatory hormones in conscious overnight fasted dogs. One group of experiments established a dose-response range. We studied the mechanisms of morphine-induced hyperglycemia in a second group. We also examined the effect of low dose morphine on glucose kinetics independent of changes in the endocrine pancreas by the use of somatostatin plus intraportal replacement of basal insulin and glucagon. In the dose-response group, morphine at 2 mg/h did not change plasma glucose, while morphine at 8 and 16 mg/h caused a hyperglycemic response. In the second group of experiments, morphine (16 mg/h) caused an increase in plasma glucose from a basal 99 +/- 3 to 154 +/- 13 mg/dl (P less than 0.05). Glucose production peaked at 3.9 +/- 0.7 vs. 2.5 +/- 0.2 mg/kg per min basally, while glucose clearance declined to 1.7 +/- 0.2 from 2.5 +/- 0.1 ml/kg per min (both P less than 0.05). Morphine increased epinephrine (1400 +/- 300 vs. 62 +/- 8 pg/ml), norepinephrine (335 +/- 66 vs. 113 +/- 10 pg/ml), glucagon (242 +/- 53 vs. 74 +/- 14 pg/ml), insulin (30 +/- 9 vs. 10 +/- 2 microU/ml), cortisol (11.1 +/- 3.3 vs. 0.9 +/- 0.2 micrograms/dl), and plasma beta-endorphin (88 +/- 27 vs. 23 +/- 6 pg/ml); all values P less than 0.05 compared with basal. These results show that morphine-induced hyperglycemia results from both stimulation of glucose production as well as inhibition of glucose clearance. These changes can be explained by rises in epinephrine, glucagon, and cortisol. These in turn are part of a widespread catabolic response initiated by high dose morphine that involves activation of the sympathetic nervous system, the endocrine pancreas, and the pituitary-adrenal axis. Also, we report the effect of a 2 mg/h infusion of morphine on glucose kinetics when the endocrine pancreas is clamped at basal levels. Under these conditions, morphine exerts a hypoglycemic effect (25% fall in plasma glucose, P less than 0.05) that is due to inhibition of glucose production (by 25-43%, P less than 0.05). The hypoglycemia was independent of detectable changes in insulin, glucagon, epinephrine and cortisol, and was not reversed by concurrent infusion of a slight molar excess of naloxone. Therefore, we postulate that the hypoglycemic effect of morphine results from the interaction of the opiate with non-mu receptors either in the liver or the central nervous system.

Journal ArticleDOI
30 Nov 1984-Science
TL;DR: The results suggest that insulin stimulates ACTH release by a mechanism in which catecholamines of peripheral origin act directly on the anterior pituitary.
Abstract: Intraperitoneal administration of insulin to control rats and to rats with pituitary stalk transections or with lesions of the median eminence resulted in increased plasma adrenocorticotropin (ACTH) levels. The insulin-induced stimulation of ACTH release was blocked in both the control and lesioned animals by prior treatment with either the beta-adrenergic antagonist propranolol or the glucocorticoid analog dexamethasone. The direct application of insulin to primary cultures of the anterior pituitary did not evoke ACTH release or affect the maximal ability of corticotropin-releasing factor or epinephrine to stimulate ACTH secretion. The results suggest that insulin stimulates ACTH release by a mechanism in which catecholamines of peripheral origin act directly on the anterior pituitary.

Journal ArticleDOI
TL;DR: The results indicate that central administration of hypertonic NaCl in dogs with intact baroreflexes causes a preferential activation of the sympathetic nervous system to vascular systems other than those of the kidneys.
Abstract: In morphine-pentobarbital anesthetized dogs (n = 25) we measured the effect of cerebroventricular administration of hypertonic sodium chloride (NaCl) on mean arterial pressure (MAP), heart rate (HR), and integrated renal nerve activity (RNA); in separate experiments (n = 9) we also evaluated the effect of hypertonic NaCl on the osmolarity and electrolyte and catecholamine concentrations of both the blood and the cerebrospinal fluid (CSF); plasma arginine vasopressin (AVP), cortisol, and renin activity were also measured. The intraventricular (ivt) injection of 1.5 M NaCl caused a hypertensive response associated with tachycardia and a significant decrease in RNA (P less than 0.001). Intravenous hexamethonium chloride prevented the changes in HR and RNA, whereas the increases in MAP were markedly reduced but not abolished. The neurohormonal effects of ivt hypertonic NaCl consisted of activation of the sympathoadrenal pituitary axis as reflected by significant increases in the plasma levels of norepinephrine (NE), epinephrine, AVP, and cortisol. On the other hand, there was a significant decrease in plasma renin activity not associated with any significant changes in plasma osmolarity and serum electrolytes. These hormonal changes coincided with an increase in the concentration of CSF NE, CSF Na+, and CSF osmolarity obtained from the cisterna magna. Altogether the results indicate that central administration of hypertonic NaCl in dogs with intact baroreflexes causes a preferential activation of the sympathetic nervous system to vascular systems other than those of the kidneys. In addition, a part of the pressor response may be due to the activation of nonneurogenic mechanisms.