Showing papers on "Epinephrine published in 1978"

The role of catecholamines in lung liquid absorption at birth.

Abstract: Summary: We have examined the effect on lung liquid secretion of catecholamines infused in chronically catheterized fetal lambs in utero. Isoproterenol and epinephrine inhibited secretion, an effect which increased with gestation and, in fetuses near delivery, caused absorption of lung liquid. In 7 out of 8 experiments nor-epinephrine had no effect on secretion. This pattern of response and the fact that the inhibitory effect could be blocked by propranolol indicate a mode of action involving β-adrenergic receptors. Speculation: The observed effects on lung liquid secretion were achieved with infusion rates of epinephrine which are well within the range for endogenous production by the adrenals in response to splanchnic nerve stimulation or asphyxia. Thus the marked increase in the secretion of epinephrine which occurs during parturition may be an important factor in initiating lung liquid absorption. Permanent inhibition of lung liquid secretion postnatally may be due to greater sensitivity of the pulmonary epithelium to β-adrenergic stimulation and to the higher “resting” output of epinephrine from the adrenals of neonates compared with fetuses.

Effect of Handling and Forced Immobilization on Rat Plasma Levels of Epinephrine, Norepinephrine, and Dopamine-β-Hydroxylase

Abstract: Forced immobilization of rats triggers activation of adrenal-medullary discharge of epinephrine (EPI) and sympathetic neuronal release of norepinephrine(NE). Plasma levels of EPI reach peak values,which are about 40-fold greater than in undisturbed rats, at about 20 min and then decline to about onethird the peak levels. Plasma levels of NE are increased bout 6-fold throughout the immobilization interval. Decapitation produces an 80-fold increase in plasma levels of EPI and an 8-fold increase in NE. These striking decapitation-induced increases are potentiated ahout 3-fold by immobilization, presumably as a consequence of an immobilization-induced alteration in the “set” of responsivity of spinal cord mechanisms controlling sympathoadrenal medullary discharge. Even minor disturbances produce highly significant increases in plasma EPI and NE and special precautions must be observed when studies involving plasma atecholaminesor their effects are performed in animals

Platelet function in essential thrombocythemia. Decreased epinephrine responsiveness associated with a deficiency of platelet alpha-adrenergic receptors.

Abstract: Platelets from two patients with essential thrombocythemia failed to aggregate or release serotonin in response to concentrations of epinephrine that aggregated platelets from normal controls. Therefore, we studied their α-adrenergic receptors, using 3H-dihydroergocryptine (3H-DHE), an α-adrenergic antagonist. These platelets contained an average (mean ± S.E.) of 210±18 and 227±27 3H-DHE binding sites per platelet — less than half that found on control platelets, 464±37 (P<0.01). In contrast, platelets from two other patients with essential thrombocythemia responded to epinephrine and contained a normal number of 3H-DHE sites. Platelets in essential thrombocythemia demonstrated normal kinetics of 3H-DHE binding and normal affinities for 3H-DHE and for epinephrine. When control platelets were preincubated with a half-saturating concentration of 3H-DHE, there was a diminution of epinephrine-induced platelet function comparable to that seen in essential thrombocythemia. Thus, a deficiency of α-adren...

Plasma Noradrenaline and Adrenaline Concentrations and Dopamine-β-hydroxylase Activity in Patients With Shock Due to Septicaemia, Trauma and Haemorrhage

Abstract: Plasma adrenaline and noradrenaline concentrations and dopamine-β-hydroxylase activities were measured in patients with septicaemic, traumatic or haemorrhagic shock. Irrespective of the type of shock plasma adrenaline and noradrenaline concentrations were increased above the normal range. This is in keeping with the clinical features of increased sympathetic nervous system and adrenal medullary activity present in these patients. Plasma dopamine-β-hydroxylase activities were within the normal limits in all forms of shock indicating the poor relationship of this measurement to sympathetic nervous system activity. In patients who died plasma noradrenaline concentrations remained persistently elevated above normal while in those who survived there was a rapid decline towards the normal range.

Centrally mediated release by cocaine of endogenous epinephrine and norepinephrine from the sympathoadrenal medullary system of unanesthetized rats.

Abstract: A radioenzymatic-paper chromatographic method for a simultaneous assay of catecholamines was used to study the effect of cocaine on the release of endogenous catecholamines from the sympathoadrenal medullary system into the blood of unanesthetized rats. Twenty-four hours after arterial cannulation, the "basal" levels of norepinephrine (NE) and epinephrine (EPI) in blood obtained through the catheter from conscious, undisturbed rats were 0.48 +/- 0.06 and 0.36 +/- 0.06 ng/ml, respectively. Administration, via the arterial catheter, of cocaine (0.4-10 mg/kg) produced dose-related increases in NE (0.59 +/- 0.03 to 1.58 +/- 0.34 ng/ml) and EPI (1.15 +/- 0.16 to 6.67 +/- 0.46 ng/ml). Inhibition of catechol O-methyltransferase by tropolone (40 mg/kg) enhanced by 5- to 10-fold the maximal response to cocaine without altering significantly the basal plasma levels of EPI or NE. Bilateral splanchnic denervation reduced the cocaine-tropolone-induced release of EPI and NE by 75 and 50%, respectively. Desipramine (10 mg/kg) failed to alter significantly plasma levels of NE or EPI, even after tropolone. Thus, the increment in plasma levels of NE and EPI in conscious rats given cocaine is mainly the result of a centrally mediated adrenal medullary discharge of catecholamines, rather than inhibition of catecholamine uptake.

The effect of epinephrine on tracheal fluid flow and surfactant efflux in fetal sheep.

Abstract: A marked decrease in fetal tracheal fluid flow and an increase in pulmonary surfactant efflux were found after infusion of epinephrine into fetal sheep. The data suggest that endogenous catecholamines may play a role in preparing the fetal lung for birth.

The Role of Cyclic Adenosine Monophosphate in Adrenergic Effects on Ventricular Vulnerability to Fibrillation in the Isolated Perfused Rat Heart

Abstract: The relation between myocardial tissue cyclic AMP (cAMP) and the vulnerability to ventricular fibrillation was assessed in the isolated perfused rat heart by measurement of ventricular fibrillation threshold (VFT) and vulnerable period duration (VP). Exogenous dibutyryl cyclic AMP (DBcAMP) reduced VFT and increased VP by a concentration-related action whereas exogenous cAMP did not. Theophylline (1.0 mmol/liter) increased the tissue content of cAMP by 58% (P < 0.001) and caused a leftward shift in the concentration-response curve to DBcAMP. An effect of cAMP on VFT and VP could be shown in the presence of phosphodiesterase inhibition by theophylline. β-1-Adrenergic receptor blockade with atenolol did not alter the concentration-response curve for VFT when DBcAMP was administered. Epinephrine (100 nmol/liter to 1 μmol/liter) also increased vulnerability to VF; this effect was accompanied by a concentration-related increase in tissue cAMP, but inconsistent changes in tissue ATP, phosphocreatine and potassium. The concentration-response curve of VFT to epinephrine was shifted leftward by theophylline and rightward by atenolol. The increases in vulnerability to fibrillation in the isolated perfused rat heart, in response to DBcAMP, theophylline or epinephrine, could be related more closely to changes of tissue cAMP than to effects on tissue high energy phosphates or potassium. The effect of epinephrine and theophylline on vulnerability to ventricular fibrillation is mediated via alterations in the intracellular level of cAMP in the isolated perfused rat heart.

Biological Properties of Islets-Activating Protein (IAP) Purified from the Culture Medium of Bordetella pertussis

Abstract: The biological activities were studied of a new protein, islets-activating protein (IAP), purified from the culture medium of Bordetella pertussis. Rats injected intravenously with 1 microgram of purified IAP exhibited markedly enhanced insulin secretory responses to glucose, glucagon, epinephrine, and sulfonylureas over a period from 3 to 10 days after the injection. The degree and duration of the enhancement were proportional to the dose of IAP; the maximal effect induced by 1-2 microgram of IAP persisted for as long as 2 months. There was a highly significant correlation between the enhancement of insulin secretion and suppression of epinephrine hyperglycemia over a wide range of doses of IAP, indicating that suppression of epinephrine hyperglycemia resulted from hypoglycemic action of insulin secreted in response to epinephrine challenge. Additional actions of IAP were observed in mice; mice treated with higher doses of IAP showed symptoms were observed when lower doses of IAP were injected into mice. Thus, it is concluded that IAP is a protein primarily possessing a unique action to potentiate insulin secretory responses of experimental animals to nutritional and hormonal stimuli.

Efficacy of dopamine, dobutamine, and epinephrine during emergence from cardiopulmonary bypass in man.

Abstract: Hemodynamic effects of dobutamine and dopamine (both 5, 10, 15 microgram/kg/min) and epinephrine (0.04 microgram/kg/min) were studied immediately following cessation of cardiopulmonary bypass in 34 patients with preoperative evidence of left ventricular dysfunction. Significant increases in mean cardiac index were seen with dobutamine (15, 25, and 26% respectively), and epinephrine (30%). The largest increases occurred with dopamine (44, 53, and 64 percent respectively). Responses varied from patient to patient, however. Seven patients developed marked output increases without concomitant increases in arterial pressure, whereas seven others showed "satisfying" increases in arterial pressure without appreciable output increases. Heart rate increases were small and few arrhythmias were noted. We conclude that dopamine, epinephrine, and dobutamine all are effective inotropic agents during the immediate post-bypass period, with variations discussed in detail. None possess the disturbing chronotropic and arrhythmogenic effects of isoproterenol (previously studied). Efficacy of administration of inotropic drugs seems best assessed by serial output measurements during this period.

Sympathetic nervous system activity in patients with subarachnoid hemorrhage.

Abstract: In patients with subarachnoid hemorrhage there were increased concentrations of plasma epinephrine and norepinephrine when compared with those concentrations in a group of patients admitted to hospital with other illness. Reassessment after a variable period showed that in patients whose eventual clinical result was poor the plasma epinephrine and norepinephrine concentrations increased further while in those with a good result those concentrations showed a decline. No such changes were evident in plasma dopamine-beta-hydroxylase activities which were within normal range. In a sub-group of patients who had neurosurgery after admission for clipping an aneurysm, the post-operative changes of plasma epinephrine and norepinephrine concentrations were related to the clinical condition of the patients.

Comparison of the pharmacological effects of epinephrine administered by the intravenous and endotracheal routes.

Abstract: Epinephrine in various dosages was administered to anesthetized dogs by intravenous and endotracheal routes. Both methods produced measurable effects on heart rate, blood pressure, and respiration. Tachycardia occurred more rapidly after endotracheal administration than after intravenous administration. Respiration appeared to be supported more advantageously with the larger endotracheal dosages. The maximum blood pressure rise was delayed only 60 seconds by the endotracheal route. With an endotracheally administered dose of ten times the intravenous dose, equal responses in blood pressure were obtained. However, when equal doses are compared, there is only a two to three fold increase with the intravenous route. Pharmacological effects were dose-related with both modes of administration. The endotracheal route may be less toxic at higher doses, affording greater safety when large amounts of epinephrine are used. It is concluded that endotracheally administered epinephrine produces significant pharmacologic effects in anesthetized dogs.

Influences on the density of beta-adrenergic receptors in the cornea and iris--ciliary body of the rabbit.

Abstract: By measurement of the specific binding of 3H-dihydroalprenolol, the densities of beta-adrenergic receptors on membranes prepared from homogenized corneas and iris--ciliary bodies of rabbits were studied. Sympathetic denervation, as a result of subconjunctival treatment with 6-hydroxydopamine, causes an increase in the density of beta-adrenergic receptors in membranes prepared from the ipsilateral iris--ciliary body but not the cornea. Topical treatment with epinephrine for 5 days causes a decrease in the density of beta-adrenergic receptors in membranes prepared from cornea and iris-ciliary body, whereas similar treatment with timolol causes an increase in the density of beta-adrenergic receptors. In the cornea, the decrease in receptor density that occurs following in vivo treatment with epinephrine is associated with a decreased ability to synthesize cyclic AMP, whereas the increase in receptor density that occurs following in vivo treatment with timolol is not associated with an altered ability to synthesize cyclic AMP. Our results indicate that the density of beta-adrenergic receptors in the anterior segment of the eye is inversely related to the level of adrenergic stimulation to the tissue but that the ability of a tissue to synthesize cyclic AMP does not necessarily parallel the change in receptor density.

Glucose, insulin, and somatostatin infusion for the determination of insulin sensitivity in vivo.

Abstract: Shen et al.1 and Reaven et al.2 have recently reported increased insulin resistance in adult-onset type diabetes based on the steady state plasma glucose (SSPG) method. In this method, epinephrine and propranolol were used to suppress endogenous insulin secretion. Epinephrine and propranolol themselves elevate SSPG levels.3 Also, plasma levels of growth hormone (HGH) and glucagon may not be suppressed under these conditions, since paradoxical rises or less suppressibility of HGH4 and glucagon5 following glucose loads have been reported in diabetic subjects. We have therefore used somatostatin, which has been shown to have no direct effect on glucose and lipid metabolism,6 to suppress endogenous secretion of insulin, glucagon, and HGH. Using the newly revised method, we have assessed insulin sensitivity in diabetics treated with diet alone, sulfonylureas, or insulin, and in obese nondiabetic subjects with hyperinsulinism.

Catecholamine response to intracranial hypertension

Abstract: Pulmonary congestion, hemorrhage, and edema, produced in the experimental animal by various methods of disturbing the central nervous system, have led to the concept that such neurogenically-initiated changes are mediated through the autonomic nervous system. Blocking the sympathetic nervous mechanisms prevents these changes. Little is found concerning the expected role of catecholamines. In this study, using a standard model of increasing intracranial pressure (ICP), intense cardiovascular changes, with blood pressure rising above 320 mm Hg and heart rate of 180 beats per minute, were noted. Within seconds, plasma catecholamine levels rose as much as 1200 times the highest normal values for epinephrine, 145 times for norepinephrine, and 35 times for dopamine. These changes occurred only when raised ICP was sustained and spatial compensation of the brain was exceeded. It is not unlikely that these events are related not only to increased ICP, but also to the effects of physical distortion of the brain stem with structural, functional, and vascular alterations within it.

Stimulation of in vitro activation and the acrosome reaction of hamster spermatozoa by catecholamines.

Abstract: Capacitation and the acrosome reaction of mammalian spermatozoa are essential for fertilization. In vitro results are presented that demonstrate that catecholamines stimulate activation (a whiplash flagellar movement characteristic of capacitated hamster spermatozoa) and the acrosome reaction. Protein-free ultrafiltrates of bovine adrenal cortex and medulla preparations stimulated motility, activation, and acrosome reactions of hamster spermatozoa in the presence of bovine serum albumin. The medulla preparation was more effective than the cortex preparation in the stimulation of activation and acrosome reactions. Epinephrine (0.5-50 μM) and norepinephrine (50.0 μM) in the presence of bovine serum albumin and a partially purified protein-free cortex preparation also stimulated activation and the acrosome reactions. Both activation and acrosome reactions in the presence of epinephrine were inhibited by the adrenergic antagonists phentolamine and propranolol, suggesting the involvement of α- and β-adrenergic receptors in the stimulation of capacitation and the acrosome reaction. In addition, phenylephrine, an α-adrenergic agonist, was as potent as epinephrine in the stimulation of acrosome reactions, but activation was reduced. Isoproterenol, a β-adrenergic agonist, was as potent as epinephrine in the stimulation of activation, but acrosome reactions were reduced. High percentages of both activation and acrosome reactions were observed only in the presence of epinephrine, norepinephrine, or phenylephrine and isoproterenol together.

Role of brainstem and spinal noradrenergic and adrenergic neurons in the development and maintenance of hypertension in spontaneously hypertensive rats.

Abstract: In young and adult spontaneously hypertensive rats (SHR), dopamine β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) activities in discrete areas of the brainstem and spinal cord were measured as indices of noradrenergic and adrenergic neuronal activities. In young SHR, the DBH activities were elevated in the locus coeruleus (LC), A2 cell area and thoracic intermediolateral cell area (IML). The elevation disappeared at adult SHR. In young SHR, no significant change of PNMT activity was observed in the A1, A2, nucleus tractus solitarii (NTS), LC and IML areas, while, in adult SHR, the PNMT activity in the A1 cell area and DBH activity in the NTS were elevated. Lowering of blood pressure by hydralazine decreased the PNMT activity elevated in the A1 cell area and elevated it in the NTS. Plasma levels of norepinephrine and epinephrine, as measured in blood samples collected via aortic cannula at resting state, were much lower than many reported values in blood collected from the decapitated trunk. In young SHR, a significant elevation of plasma norepinephrine and DBH levels was confirmed as signs of peripheral sympathetic nervous activation. The elevation disappeared at adult SHR. Plasma epinephrine levels raised under restraint stress were much higher in SHR at all ages than in normotensive controls. In young SHR, the selective activation of noradrenergic neurons of the IML, A2 and LC areas, accompanied by activation of the peripheral sympathetic nervous system, initiates the hypertension. In adult SHR, the activation of adrenergic neurons in the A1 cell area including the nucleus reticularis lateralis may not be involved in the maintenance of hypertension but may be the results of hypertension.

Effects of ketamine on brain monoamine levels in rats.

Abstract: The effects of ketamine (50 mg/kg i.p.) on brain monoamines, including epinephrine, norepinephrine, dopamine, serotonin and its metabolite 5-hydroxy indoleacetic acid, were studied in three groups of male Sprague-Dawley rats. A rapid, simple, accurate, and sensitive spectrophotoflurometric method was developed to determine monoamines extracted from rat brain. Ketamine significantly increased brain epinephrine (25%), serotonin (28%) and 5-hydroxy indoleacetic acid (32%) in rats. In contrast, norepinephrine (43%) and dopamine (58%) levels were significantly reduced at 30 minutes. The increase in epinephrine (13%) and decrease in norepinephrine (31%) and dopamine (38%) levels remained significant 12 hours after ketamine injection. Serotonin and 5-hydroxy indoleacetic acid levels returned to almost normal in ketamine pretreated animals after 12 hours. Thus, the ability of ketamine to interfere with monoamine metabolism was revealed.

Parathyroid Hormone Responses to Catecholamines and to Changes of Extracellular Calcium in Cows

Abstract: Modifications of the plasma level of immunoreactive parathyroid hormone (PTH) in cattle were induced by changes of the plasma concentrations of epinephrine, isoproterenol, or calcium. During abrupt hypocalcemia, PTH, obtained by infusions with ethylene glycol-bis (β-aminoethylether) N, N′-tetraacetate (EGTA), increased during the first 4-8 min. After a transient decline, the hormone levels rose again and remained elevated. Infusions of calcium suppressed the hypocalcemia-induced augmentation of PTH levels within a few minutes. Prolonged epinephrine (and isoproterenol) infusions also rapidly increased PTH levels, however, in this case, they returned to basal concentrations after 50-60 min. Additional epinephrine infusions could not further raise PTH values. Moreover, three short-lasting infusions of epinephrine (7 min each), given at 30-min intervals, increased PTH levels to the same extent, whereas additional infusions were much less effective. The PTH response to epinephrine was completely restored, when the interval after a prolonged epinephrine infusion had been prolonged to > 100 min. During moderate hypocalcemia, occurring at the end of EGTA infusions and lasting for 90 min, the PTH response to a short-lasting epinephrine infusion (7 min) was more pronounced than in normocalcemic animals. During severe hypocalcemia, in which superimposed short-lasting infusions of EGTA (7 min) led to an additional abrupt fall of plasma calcium concentrations but not to a corresponding additional rise of the PTH levels, epinephrine rapidly and further increased PTH concentrations. On the other hand, at the end of prolonged infusions of epinephrine, when additional infusions of epinephrine were ineffective in raising PTH levels, EGTA-induced hypocalcemia consistently increased PTH concentrations. The EGTA-induced augmentation of PTH levels was enhanced by epinephrine and isoproterenol but not by propranolol. The present findings indicate, that variations of the extracellular calcium concentrations and β-adrenergic agonists modify PTH levels by two different and independent mechanisms. On the other hand, it appears that the magnitude of change of the PTH levels to either stimulus is partially modulated by exposure to the other.

α-Adrenergic Inhibition of Adenosine 3′,5′-Monophosphate Accumulation and Parathyroid Hormone Release from Dispersed Bovine Parathyroid Cells

Abstract: The possibility of alpha-adrenergic modulation of cAMP accumulation and parathyroid hormone (PTH) release was investigated in dispersed bovine parathyroid cells. cAMP accumulation due to the mixed alpha- and beta-adrenergic agonists, (-)epinephrine and (-)norepinephrine, was significantly enhanced by the alpha-adrenergic inhibitor phentolamine; that due to the "pure" beta-adrenergic agonist, (-)isoproterenol, was not altered significantly. Direct inhibition of agonist-stimulated cAMP accumulation was effected by adding increasing concentrations of (-)epinephrine to concentrations of (-)isoproterenol maximally stimulating cAMP accumulation. A 50-75% inhibition of cAMP was observed which was specifically blocked by phentolamine. This inhibition was not specific for beta-adrenergic stimulation, as (-)epinephrine also inhibited dopamine-stimulated cAMP accumulation. The inhibition of (-)isoproterenol-stimulated cAMP accumulation by (-)epinephrine was unaffected by ambient calcium concentration. Stimulation of PTH release by (-)epinephrine and (-)norepinephrine was potentiated by phentolamine and inhibited by the beta-adrenergic blocker, (-)propranolol, demonstrating alpha-adrenergic modulation of hormone release and confirming the close relationship between cAMP accumulation and PTH release previously shown in this system. These results demonstrate the presence of an alpha-adrenergic receptor in dispersed bovine parathyroid cells which inhibits agonist-stimulated cAMP accumulation and PTH release by a mechanism independent of extracellular calcium.