Showing papers on "Epinephrine published in 1982"
TL;DR: It is demonstrated that CRF acts within the brain to stimulate sympathetic outflow, which results in the development of hyperglycemia, which is secondary to the enhanced secretion of both epinephrine and norepinephrine.
Abstract: Corticotropin-releasing factor (CRF) injected into the brains of rats produces hyperglycemia and an increase in plasma concentrations of glucagon, epinephrine, and norepinephrine. Neither hypophysectomy nor adrenalectomy prevents CRF-induced hyperglycemia. However, a role of adrenal epinephrine release in mediating CRF-induced hyperglycemia is supported by the finding that the central nervous system-selective somatostatin analog, desAA1,2,4,5,12,13-[D-Trp8]somatostatin, totally prevents the elevation of plasma epinephrine and suppresses the rise of plasma glucose but does not alter the increase in plasma norepinephrine induced by CRF. Pretreatment with the ganglionic blocker chlorisondamine completely prevents the CRF-induced rises in plasma glucose, epinephrine, and norepinephrine. These results demonstrate that CRF acts within the brain to stimulate sympathetic outflow, which results in the development of hyperglycemia. In contrast to other peptides that act within the central nervous system, e.g. bombe...
652 citations
TL;DR: A large number of studies have shown that norepinephrine acts primarily as a neurotransmitter released from sympathetic-nerve regions of the nervous system and epinephrine acts as a “feel-good” hormone.
Abstract: THE catecholamines norepinephrine and epinephrine are key regulators of many physiologic events in human beings; norepinephrine acts primarily as a neurotransmitter released from sympathetic-nerve ...
387 citations
TL;DR: The results show that the vasomotor effects on regional flows are mediated both via adrenergic mechanisms, and in the case of skeletal muscle and kidney, via mechanisms unrelated to sympathetic stimulation.
Abstract: Cardiovascular actions of insulin were studied by intravenous infusions of insulin (4 and 8 mU/kg per min) in normal conscious dogs. This resulted in increases in cardiac output, heart rate, and left ventricular derivative of pressure with respect to time (dP/dt) and dP/dt/P, as blood glucose was reduced. The inotropic and chronotropic effects of insulin were not related to hypoglycemia, as they persisted even when blood glucose was restored to control values or when it was prevented from falling by a simultaneous infusion of glucose. These cardiac effects were accompanied by increases in plasma catecholamines, and were abolished by propranolol pretreatment. Both plasma epinephrine and norepinephrine increased during insulin hypoglycemia, but only norepinephrine increased during insulin infusion when euglycemia was maintained.
Mean arterial blood pressure did not change significantly during insulin hypoglycemia, but rose if euglycemia was maintained, probably due to the selective increase in norepinephrine in the latter condition. A pressor response also occurred in propranolol-pretreated dogs during insulin hypoglycemia, but was abolished when the animals also had been pretreated with phentolamine, indicating that the vasoconstrictor action of insulin was mediated via alpha adrenergic receptors.
Insulin infusion increased left ventricular work and myocardial blood flow in dogs with and without hypoglycemia. Myocardial blood flow, however, did not change significantly during insulin infusion in dogs pretreated with propranolol. As propranolol also diminished the inotropic response, it appears that the increase in myocardial blood flow caused by insulin in the normal dog is causally related to the increased myocardial metabolic demand.
Insulin also produced vasomotor effects on other vascular beds. In skeletal muscle, blood flow was increased under all study conditions, except during insulin hypoglycemia after propranolol-pretreatment when unopposed alpha-mediated vasoconstriction was present. The persistent increase in flow during both alpha and beta adrenergic blockade suggests that insulin has a direct dilator effect on skeletal muscle vasculature. In the adrenal gland, flow was increased except during euglycemia, when no rise in plasma epinephrine was observed, suggesting coupling between adrenal flow and catecholamine release. In the splanchnic bed, flow was decreased during euglycemia, when plasma norepinephrine rose, and during beta adrenergic blockade with propranolol, when unopposed alpha-mediated vasoconstriction also predominated. A similar pattern was found in the kidney, except that renal blood flow also fell after combined alpha and beta adrenergic blockade. The results show that the vasomotor effects on regional flows are mediated both via adrenergic mechanisms, and in the case of skeletal muscle and kidney, via mechanisms unrelated to sympathetic stimulation.
291 citations
TL;DR: Corticotropin-releasing factor administered intracerebroventricularly produces prolonged elevation of plasma concentration of epinephrine, norepinephrine and glucose, associated with an increase in motor activity and oxygen consumption.
258 citations
TL;DR: Epinephrine increased oxygen consumption and glucose uptake in both resting and electrically stimulated hindquarters and, under some conditions, it had a positive inotropic effect on contracting muscle.
Abstract: The interaction of epinephrine and contractions on muscle metabolism was studied in the isolated perfused rat hindquarter. Subtetanic contractions (180/min) through 20 min elicited glycogenolysis and increased phosphorylase a activity. In the soleus, a slow-twitch red muscle, these effects were transient, but when epinephrine at a physiological concentration (2.4 X 10(-8) M) was added to the perfusate, glycogenolysis and phosphorylase activity were sustained throughout contractions. At this high frequency of contractions, the effect of epinephrine was much smaller in the fast-twitch red fibers and not significant in the fast-twitch white fibers of the gastrocnemius muscle. However, during less frequent contractions (30/min) epinephrine increased glycogenolysis and phosphorylase a activity in fast-twitch muscle. The data suggest that epinephrine and muscle contractions exert a dual control of muscle glycogenolysis during exercise: contractions principally stimulate glycogenolysis early in exercise, and a direct effect of epinephrine on muscle is needed for continued glycogenolysis. In addition, epinephrine increased oxygen consumption and glucose uptake in both resting and electrically stimulated hindquarters and, under some conditions, it had a positive inotropic effect on contracting muscle.
220 citations
TL;DR: The results suggest that hypothalamic epinephrine concentration and turnover are particularly responsive to acute and chronic stress, and may be responsible for the behavioral and endocrine changes observed in chronically stressed rats.
210 citations
TL;DR: The elimination of sympathetic recruitment by diazepam‐induced sedation, however, without concomitant reductions in heart rate or systolic pressure responses, suggests that other systems besides the sympathetic nervous system influence the circulatory response to this real‐life stress.
Abstract: We studied the circulatory, psychological, plasma catecholamine, cortisol, and lipid responses to a real-life stress--third molar extractions--in 21 patients and the effects of sedation with intravenous diazepam and of inclusion of epinephrine with the local anesthetic. Across all patients, the surgery was associated with significantly increased heart rate (25%), systolic blood pressure (13%) and cardiac output--as indicated using impedance cardiography (34%)--without a significant change in diastolic blood pressure. Plasma norepinephrine increased by 60% during the surgery in nonsedated patients. Diazepam sedation abolished the norepinephrine response to the surgery, without significantly affecting the heart rate or systolic pressure responses. Receipt of epinephrine with the local anesthetic resulted in a fivefold increase in mean plasma epinephrine 5 min after the injection, as well as increased cardiac output. The direct effect of epinephrine accounted for the cardiac output increase observed during the surgery. The results suggest the participation of the sympathetic nervous system in producing the circulatory responses to dental surgery. The elimination of sympathetic recruitment by diazepam-induced sedation, however, without concomitant reductions in heart rate or systolic pressure responses, suggests that other systems besides the sympathetic nervous system influence the circulatory response to this real-life stress.
200 citations
TL;DR: There is a disturbance in the sympathetic nervous system during exercise in patients with congestive heart failure, although norepinephrine increases in such patients to a greater extent than in normal subjects at lower levels of exercise, and the extremely high levels of norpinephrine and epinephrine generated by normal subjects during maximal upright exercise do not occur in Patients with heart failure.
Abstract: The activity of the sympathetic nervous system is increased at rest in patients with congestive heart failure. To determine whether this augmentation is carried over during dynamic upright exercise, 14 patients with congestive heart failure were stressed maximally during upright bicycle ergometry. Plasma norepinephrine and epinephrine levels were measured in the basal upright (sitting) posture before and during maximal exercise. The results were compared with those in six healthy control subjects before and during maximal exercise. Plasma norepinephrine increased during exercise from a mean (+/- standard error of the mean) of 650 +/- 95 to 1,721 +/- pg/ml in the group with heart failure. This increase was significantly less (p less than 0.001) than that in the control group (from 318 +/- 36 to 3,230 +/- 418 pg/ml). However, for equivalent levels of total body oxygen consumption (VO2), the group with heart failure had higher levels of plasma norepinephrine than the control group. Plasma epinephrine was similar in the two groups in the basal upright position (92 +/- 18 and 92 +/- 26 pg/ml), but it increased more during exercise in the normal subjects (743 +/- 210 pg/ml) than in the group with heart failure (167 +/- 67 pg/ml) (p less than 0.001). The percent increase in norepinephrine correlated with the percent change in VO2 in the group with heart failure (r = 0.62, p less than 0.02), but the percent change in epinephrine did not. There is, therefore, a disturbance in the sympathetic nervous system during exercise in patients with congestive heart failure. Although norepinephrine increases in such patients to a greater extent than in normal subjects at lower levels of exercise, the extremely high levels of norepinephrine and epinephrine generated by normal subjects during maximal upright exercise do not occur in patients with heart failure.
179 citations
TL;DR: It is shown that two thirds of patients with diabetic autonomic neuropathy have moderate to severe deficits in epinephrine secretion and that these patients have diminished or delayed subjective responses to low blood sugar and are at risk for developing severe hypoglycemia and its neurologic consequences.
Abstract: The cause of the susceptibility of certain diabetic patients to severe hypoglycemia is not known. Because the awareness of hypoglycemia is heightened by catecholamine-mediated physiologic ...
171 citations
TL;DR: Although the hemodynamic responses to lidocaine plus epinephrine in these healthy young adults were small, the significant increase of systemic plasmaEpinephrine concentrations suggests that high-risk patients who receive this type of anesthesia should be monitored carefully.
Abstract: Effects of dental injection of local anesthetic on arterial plasma epinephrine concentrations and cardiovascular function were assessed. High-risk patients receiving local anesthetic with epinephrine should be monitored carefully.
148 citations
TL;DR: The data suggest that the increased numbers of β-adrenergic receptors in canine LV ischemic tissue are capable of translating physiological responses when they are activated with an appropriate agonist in vivo.
Abstract: In the present study, we evaluated the physiological responsiveness of the increased numbers of beta-adrenergic receptors in ischemic canine myocardium to in vivo stimulation by (-)-isoproterenol and epinephrine. After 1 hour of temporary proximal left anterior descending coronary artery occlusion and during a 15-minute period of reflow, dogs received (1)-isoproterenol intravenously at a rate sufficient to increase their heart rates 20--40 beats/min. Following the infusion of isoproterenol, myocardial tissue was obtained from the LV ischemic and nonischemic regions for measurement of beta-adrenergic receptor numbers, cyclic AMP content, and phosphorylase b to a conversion. beta-Adrenergic receptor numbers were significantly increased in the left ventricular (LV) ischemic tissue. The administration of (-)-isoproterenol was associated with significant increases in cyclic adenosine monophosphate content and phosphorylase b to a conversion in the LV ischemic tissue. Also, the administration of (-)-epinephrine significantly increased the phosphorylase b to a conversion in ischemic tissue over the nonischemic tissue and this conversion was blocked by pretreatment with (+/-)-propranolol. These data suggest that, in this experimental model, the increased numbers of beta-adrenergic receptors in canine LV ischemic tissue are capable of translating physiological responses when they are activated with an appropriate agonist in vivo.
TL;DR: A receptor-mediated mechanism for the fine regulation of secretion from the adrenal medulla is suggested, which involves an in situ collagenase perfusion affecting only the connective tissue matrix of the medulla while leaving the cortex intact.
Abstract: The regulation of secretion of catecholamines from bovine adrenal medulla cells was investigated by use of an improved and highly efficient method for isolating viable and responsive cells from this tissue. The method involves an in situ collagenase perfusion affecting only the connective tissue matrix of the medulla while leaving the cortex intact. The cells released both epinephrine and norepinephrine in response to stimulation by 100 μM acetylcholine. The ratio of epinephrine to norepinephrine in the medium following non-stimulated (basal) release, was similar to that found in the intact cells. On the other hand, a lower ratio of epinephrine to norepinephrine was found in the medium following stimulation by acetylcholine due mainly to preferential secretion of norepinephrine. This release ceased after 15 min of incubation and consisted of 15–20% of the catecholamines initially present in the cells. Exogenous epinephrine was found to inhibit total catecholamine secretion; however, it stimulated norepinephrine release. Addition of isoproterenol caused a stimulation of release while propranolol was inhibitory. Norepinephrine inhibited total release not favoring any specific catechol. Other α-agonists, such as clonidine, also had an inhibitory effect. These results suggest a receptor-mediated mechanism for the fine regulation of secretion from the adrenal medulla.
TL;DR: The mammary glands of mammals from the platypus to man are identical in fine structure, and consist of alveolar tissue within which milk is continuously secreted during lactation; the establishment of a nervous link between the nipple and the oxytocinergic neurones of the hypothalamus allows milk ejection from the alveolars to be co-ordinated with the sucking of the young.
Abstract: The mammary glands of mammals from the platypus to man are identical in fine structure, and consist of alveolar tissue within which milk is continuously secreted during lactation. An alveolar structure increases enormously (perhaps by 10 000-fold) the surface area for secretion relative to the external size of the gland, but at the same time complicates the problem of milk removal. Small ducts generate substantial surface tension forces that oppose the movement of fluids: suction is therefore a relatively ineffective method for removal of alveolar milk. The problem has been overcome by investing the alveoli in a basket-like reticulum of myoepithelium which contracts in response to oxytocin released from the posterior pituitary. When stimulated by oxytocin the alveoli are compressed and milk is expelled into the larger collecting ducts for removal by the sucking of the young. Further, the establishment of a nervous link between the nipple and the oxytocinergic neurones of the hypothalamus allows milk ejection from the alveolar tissue to be co-ordinated with the sucking of the young. Thus is formed the most classical of neuroendocrine reflexes. Our analysis of this reflex would, if we adopted a traditional approach, commence with the sensory input to the hypothalamus (afferent limb) and conclude with a study of the motor response, i.e. the release of oxytocin and milk ejection (efferent limb). There are however sound reasons for reversing this procedure. The process of milk ejection is remarkably uniform in all mammals, but the same cannot be said of the afferent limb of the reflex arc. Two of the laboratory animals make a good comparison in this respect (Text-fig. 1).
TL;DR: The results are consistent with the co-storage of opioid peptides and opiate receptor-inactive peptides containing enkephalin sequences in chromaffin vesicles and with the all- or-none exocytotic secretion of chromaff in vesicle content in response to stimulation of the adrenal medulla.
Abstract: Bovine adrenal medullary chromaffin cells were used to study the relationship between opioid peptide and catecholamine secretion from the adrenal medulla. Stimulation of chromaffin cells by acetylcholine, nicotine, veratridine, barium, or Ionomycin produced secretion of opioid peptides and catecholamines which was proportional to the cellular content of these substances. Nicotine-evoked secretion of opioid peptides and catecholamines was dependent on extracellular calcium and was blocked by d-tubocurarine. Increased cellular content of opioid peptides and decreased catecholamine content induced by treatment of chromaffin cells with reserpine or tetrabenazine were reflected in the secretion of proportionally larger amounts of opioid peptides and smaller amounts of catecholamines when compared with secretion of these substances from untreated cells. Peptides of up to 25,000 daltons that express opiate activity only following digestion with enzymes, such s trypsin and carboxypeptidase B, also are secreted from chromaffin cells in the same proportion of their cellular content as are catecholamines and opioid peptides. Opioid peptides were secreted in proportion to total catecholamines but not in proportion to either epinephrine or norepinephrine alone, suggesting that the peptides are secreted from both epinephrine- and norepinephrine- containing cells in the cultures. The results are consistent with the co-storage of opioid peptides and opiate receptor-inactive peptides containing enkephalin sequences in chromaffin vesicles and with the all- or-none exocytotic secretion of chromaffin vesicles content in response to stimulation of the adrenal medulla.
TL;DR: It is concluded that, in females, epinephrine utilizes both alpha- and beta-adrenergic pathways which activate phosphorylase by calcium or cAMP, respectively, while, in adult male rats,Epinephrine increases phosphoryLase alpha activity by an alpha-mediated, calcium-dependent and cAMP-independent pathway.
TL;DR: Data suggest that circulating epinephrine, originating in the adrenal medulla, is taken up by sympathetic nerve terminals innervating blood vessels and acts like a classical neurotransmitter, producing vasodilation in skeletal muscle and vasoconstriction in splanchnic and renal vascular beds.
Abstract: We examined the neurohumoral mechanisms underlying the hindlimb vasodilator response produced by electrical stimulation of the anteroventral region of the third ventricle (AV3V). Hindlimb blood flow velocity was recorded using a pulsed Doppler flow probe. The vasodilator response to AV3V stimulation was greater than that obtained after inhibition of neurogenic vasoconstrictor tone with sympathectomy and was, therefore, in part an active process. The hindlimb vasodilator response was not affected by cholinergic or histaminergic receptor blockade but was reduced by bilateral adrenalectomy (ADX) or adrenal demedullation (ADM) and was further reduced by beta-adrenergic receptor blockade with propranolol in ADX rats. In ADX or ADM rats the vasodilator response was attenuated by repeated AV3V stimulations and restored by epinephrine infusion. Moreover, restoration of the response after epinephrine infusion was completely blocked by the neuronal uptake blocker desmethylimipramine. As was observed with vasodilation, constrictor responses to AV3V stimulation in the renal and mesenteric vascular beds were also attenuated by adrenal demedullation and were restored by epinephrine infusion. These data suggest that circulating epinephrine, originating in the adrenal medulla, is taken up by sympathetic nerve terminals innervating blood vessels. The catecholamine is then released from these nerves and acts like a classical neurotransmitter, producing vasodilation in skeletal muscle and vasoconstriction in splanchnic and renal vascular beds.
TL;DR: Conclusions are concluded that circulating epinephrine can stimulate pituitary-adrenocortical activity, this action is mediated by a beta-ADrenergic receptor mechanism, and such a mechanism may be involved in the response of the pituitsary- adrenal axis during certain forms of stress.
Abstract: Epinephrine or isoproterenol was infused into a lateral tail vein of female Wistar rats under Nembutal anesthesia. After 20 min of diffusion, trunk blood was collected for the determination of plasma corticosterone (B) and ACTH immunoreactivity (ACTHi). Infusion of l-epinephrine resulted in a dose-related increase in plasma ACTHi and B. Maximal levels were similar to those observed during ether stress. The pituitary-adrenal system appeared more sensitive than the cardiovascular system to epinephrine, since the ED50 values of epinephrine for its effects on ACTHi and heart rate were 165 and 840 ng/kg . min, respectively. The effect of epinephrine on pituitary-adrenal activity could be mimicked by the beta-adrenergic agonist l-isoproterenol and could be blocked by the beta-adrenergic antagonist l-propranolol, whereas d-propranolol was ineffective. The response of the pituitary-adrenal system to epinephrine was not caused by effects on peripheral parameters such as the distribution or clearance of ACTH or B but was mediated by an increase in ACTH release. The pituitary-adrenal response to epinephrine and isoproterenol was not related to changes in heart rate, blood pressure, or vasopressin secretion. Infusion of epinephrine at a dose that induced a maximal increase in plasma ACTHi and B (1000 ng/kg . min) resulted in a circulating epinephrine concentration of 11 pmol/ml, which is within the physiological range. From these data we conclude that 1) circulating epinephrine can stimulate pituitary-adrenocortical activity, 2) this action is mediated by a beta-adrenergic receptor mechanism, and 3) such a mechanism may be involved in the response of the pituitary-adrenal axis during certain forms of stress.
TL;DR: The continued study of drugs affecting epinephrine neurons should be useful in elucidating functions of these neurons, which may be of use in the treatment of hypertension, psychiatric disorders, neuroendocrine dysfunction, and possibly other diseases.
Abstract: Neurons that contain PNMT, the epinephrine-forming enzyme, have their cell bodies in brain stem regions in rat brain and send projections mainly into other brain stem areas, hypothalamus, and spinal cord. These neurons can be affected pharmacologically by various kinds of drugs. Epinephrine neuronal systems might play a part in some pharmacologic actions of MAO inhibitors and uptake inhibitors as well as alpha and beta agonists and antagonists. PNMT inhibitors currently represent the only means of modifying epinephrine neurons pharmacologically without also altering norepinephrine or dopamine neurons in brain. The continued study of drugs affecting epinephrine neurons should be useful in elucidating functions of these neurons. Drugs that affect epinephrine neurons may be of use in the treatment of hypertension, psychiatric disorders, neuroendocrine dysfunction, and possibly other diseases.
TL;DR: Results indicate that central nervous system glucose metabolism may mediate diet-induced changes in SNS activity, which is independent of adrenal medullary catecholamine release.
Abstract: In rats and mice, fasting suppresses and sucrose overfeeding stimulates sympathetic nervous system (SNS) activity. Fasting hypoglycemia in rats suppresses SNS activity while stimulating adrenal medullary catecholamine release. Administration of 2-deoxy-D-glucose (2-DG), an inhibitor of intracellular glucose metabolism, also stimulates the adrenal medulla. The studies reported here were undertaken to determine the SNS response to chronic 2-DG administration and to test the hypothesis that diet-induced changes in SNS activity are related to central nervous system glucose metabolism. Ingestion of 2-DG caused an increase in urinary epinephrine excretion and significant depletion of adrenal epinephrine content, both indices of adrenal medullary stimulation. Chronic sc injections of 2-DG in animals with normal or increased food consumption caused simultaneous suppression of cardiac sympathetic nerve activity, as evidenced by diminished cardiac [3H]norepinephrine turnover, and stimulation of adrenal medullary epinephrine release. Parenteral 2-DG administration to adrenalectomized rats also caused suppression of cardiac sympathetic activity. Thus, this response to neuroglycopenia is independent of adrenal medullary catecholamine release. These results indicate that central nervous system glucose metabolism may mediate diet-induced changes in SNS activity.
TL;DR: The results indicate that epinephrine has profound effects on contracting muscle, and that these effects are elicited through different combinations of alpha- and beta-adrenergic receptor stimulation.
Abstract: The role of alpha- and beta-adrenergic receptor stimulation for the effect of epinephrine on muscle glycogenolysis, glucose- and oxygen uptake and muscle performance was studied in the perfused rat hindquarter at rest and during electrical stimulation (60 contractions/min) Adrenergic stimulation was obtained by epinephrine in a physiological concentration (24 X 10(-8) M) and alpha- and beta-adrenergic blockade by 10(-5) M phentolamine and propranolol, respectively Epinephrine enhanced net glycogenolysis during contractions most markedly in slow-twitch red fibers In these fibers the effect was mediated by alpha- as well as by beta-adrenergic stimulation, the latter involving production of cAMP, phosphorylase activation and synthase inactivation In contrast, in fast-twitch fibers only beta-adrenergic mechanisms were involved in the glycogenolytic effect of epinephrine Moreover, inactivation of synthase was less in these fibers Epinephrine also increased the net release of lactate from the hindquarter, an effect abolished by combined alpha- and beta-adrenergic blockade but by neither alpha- nor beta-adrenergic blockade alone Epinephrine increased uptake of oxygen and glucose by stimulation of alpha-adrenergic receptors and had a positive inotropic effect during contractions which was abolished by alpha- as well as by beta-adrenergic blockade The results indicate that epinephrine has profound effects on contracting muscle, and that these effects are elicited through different combinations of alpha- and beta-adrenergic receptor stimulation
Journal Article•
TL;DR: Urethane inhibits cardiovascular responses that are mediated by peripheral and central alpha-2 adrenoceptors and decreases the pressor responses evoked by clonidine, oxymetazoline and norepinephrine which stimulate both alpha-1 and alpha- 2 adrenoceptor agonists.
Abstract: Clonidine and oxymetazoline (4.0 microgram/kg i.v. or i.a.) evoked a marked bradycardia in either methylatropine-pretreated conscious or pentobarbital-anesthetized (55 mg/kg i.p.), vagotomized rats. Urethane (1.2 g/kg i.p.) inhibited by more than 50% this effect which is mediated through the stimulation of peripheral and/or central neuronal alpha-2 adrenoceptors. However, in adrenalectomized rats only the inhibition of oxymetazoline by urethane was significantly less pronounced. In pithed rats in which the adrenal glands were either left untouched or surgically removed, urethane significantly attenuated the clonidine or oxymetazoline-induced decreases in experimental neural sympathetic tachycardia although it neither changed the base-line nor the experimentally elevated heart rate. Urethane, in contrast to pentobarbital, increased plasma epinephrine concentrations in intact but not in adrenalectomized or in pithed rats. Elevation of plasma epinephrine did not result from the low arterial pressure level associated with urethane anesthesia since the increase of this parameter with vasopressin did not abolish the effect of urethane. Furthermore, guanethidine-pretreated rats, when anesthetized with urethane, exhibited a higher heart rate and plasma adrenaline value than those anesthetized with pentobarbital. The elevated heart rate was decreased by either propranolol or adrenalectomy. The bradycardia produced by injecting clonidine into the lateral cerebral ventricles of either intact or adrenalectomized rats was markedly less in urethane- than in pentobarbital-anesthetized animals. Whereas in pentobarbital-anesthetized rats the peak heart rate effects of i.v. or i.c.v. clonidine were similar, in urethane-anesthetized animals the effects of clonidine were more inhibited when it was given centrally than when it was given peripherally. In pithed rats, the cumulative dose-pressor response curves elicited by the relatively selective alpha-2 adrenoceptor agonists, B-HT 930 and M-7, were depressed by urethane significantly more than those produced by the relatively selective alpha-1 adrenoceptor agonists, phenylephrine and cirazoline, or by angiotensin II. Urethane also decreased the pressor responses evoked by clonidine, oxymetazoline and norepinephrine which stimulate both alpha-1 and alpha-2 adrenoceptors. However, the extent of this inhibition was less than that of B-HT 920 and M-7 but greater than that of cirazoline and phenylephrine. These results show that urethane inhibits cardiovascular responses that are mediated by peripheral and central alpha-2 adrenoceptors. Furthermore, urethane increases the central drive to the adrenal medulla and this leads to the secretion of epinephrine. This may be partly responsible for the inhibitory activity of urethane on oxymetazoline-induced bradycardia. Although the basic mechanism by which urethane impairs responses mediated by alpha-2 adrenoceptors remains to be determined, it is advised that urethane anesthesia should be avoided, particularly for cardiovascular studies.
Journal Article•
TL;DR: In this article, the authors measured umbilical arterial plasma norepinephrine and epinephrine using a sensitive radioenzymatic assay and found significant correlations with fetal heart rate tracings, durations of labor, duration of rupture of the membranes, and fetal sex.
Journal Article•
TL;DR: The receptors involved in the pressor and tachycardic effects of catecholamines applied systemically or released from sympathetic nerve endings were compared and alpha-1, alpha-2, beta-1 and beta-2 adrenoceptors activated as demonstrated in pithed rats were compared.
Abstract: The receptors involved in the pressor and tachycardic effects of catecholamines applied systemically or released from sympathetic nerve endings were compared. Intravenously administered (-)-epinephrine activated alpha-1, alpha-2, beta-1 and beta-2 adrenoceptors as demonstrated in pithed rats, using the alpha-1 sympatholytic drug prazosin, the alpha-2 adrenoceptor blocking substance rauwolscine, the beta-1 and beta-2 sympatholytic agent(-)-propranolol, the predominantly beta-1 adrenoceptor antagonist atenolol and the selective beta-2 adrenoceptor blocking agent ICI 118,551 as tools. (-)-Norepinephrine given i.v. proved to be an alpha-1, alpha-2 and beta-1 adrenoceptor agonist. 1,1-Dimethyl-4-phenylpiperazine iodide (DMPP) releases catecholamines from noradrenergic neurons and the adrenal medulla. The i.v. injection of DMPP into pithed rats caused an increase in diastolic pressure and heart rate by this indirect effect, which has been confirmed by pretreatment with reserpine and removal of the adrenals. After bilateral adrenalectomy, there occurred a release of mainly norepinephrine, only from the neurons. Catecholamines liberated by DMPP activated alpha-1 and beta-1 receptors and, at high doses of DMPP, alpha-2 and beta-2 adrenoceptors as well. Removal of both adrenal glands abolished the alpha-2 and beta-2 adrenoceptor-mediated effects. (-)-Norepinephrine released from neurons stimulated alpha-1 and beta-1 adrenoceptors only, although after i.v. administration of this catecholamine alpha-2 adrenoceptors were also activated. There was no indication for a beta-2 adrenoceptor-mediated vasodilation by neuronally released catecholamines. A beta-2 adrenoceptor-mediated effect, however, could be demonstrated by i.v. injection of (-)-epinephrine. The results can be explained by the presence of predominantly alpha-1 and beta-1 adrenoceptors in the postganglionic sympathetic synapses and an extrasynaptic location of alpha-2 and beta-2 adrenoceptors. The extrasynaptic receptors are possibly controlled by epinephrine from the adrenals.
TL;DR: Arterial levels of both epinephrine and norepinephrine exceeded venous levels significantly, suggesting the adrenal medulla as a major source of these substances during hypoxemia, and similar qualitative relations between catecholamines and PO2 were evident at all gestational ages.
Abstract: Changes in peripheral plasma catecholamines were studied during varying degrees of hypoxemia in fetal lambs of 95–140 days gestation. Epinephrine and norepinephrine concentrations were measured by radioenzymatic assay in plasma obtained simultaneously from the distal aorta and inferior vena cava in 15 chronically catheterized fetuses with the mother breathing 20, 10, or 8% oxygen mixtures. Levels of both epinephrine and norepinephrine increased significantly after 5 min of hypoxemia and showed a strong inverse exponential correlation with PO2 (P less than 0.001). Plasma norepinephrine always exceeded epinephrine concentrations (P less than 0.01). Resting arterial and venous catecholamine levels were not different, but during hypoxemia arterial levels of both epinephrine and norepinephrine exceeded venous levels significantly, suggesting the adrenal medulla as a major source of these substances. Hypoxemia led to fetal bradycardia, the degree of which moderated somewhat with extremely low oxygen tensions and associated very high catecholamine levels. Fetal blood pressure increased initially in proportion to norepinephrine levels but reached a plateau at concentrations higher than 10 ng/ml. Although concentrations of catecholamines were lower in the earlier gestation fetuses studied, similar qualitative relations between catecholamines and PO2 were evident at all gestational ages.
TL;DR: It is concluded that proximity to the adrenal cortex is not necessary for initial expression of PNMT, and initial expression was not dependent on high local concentrations of glucocorticoids, whereas subsequent development did require high levels of the hormones.
TL;DR: A few selected areas of active research where radioligand binding techinques have been applied to the study of adrenergic receptors in the heart are discussed.
Abstract: Introduction Catecholamines, acting through alphaand beta-adrenergic receptors, modulate a variety of physiological responses in the heart. Most impor tantly catecholamines increase the rate and force of cardiac contraction. These actions occur mainly as a consequence of the binding of the endoge nous substances norepinephrine and epinephrine to specific adrenergic receptors on the plasma membrane of cells in the heart. Whereas the effects of sympathetic nervous stimulation on the heart have been examined for many years (reviewed in 57), oIlly recently has it become possible to mea sure directly the properties of the receptors for catecholamines in the heart. Here we discuss a few selected areas of active research where radioligand binding techinques have been applied to the study of adrenergic receptors in the heart.
TL;DR: Rat adrenal chromaffin cells undergo age-related changes in both structural and functional plasticity and appear to be previously unreported NGF targets which require NGF for survival or process outgrowth.
Abstract: Normal postnatal rat chromaffin cells and rat pheochromocytoma cells are known to show extensive Nerve Growth Factor (NGF)-induced process outgrowth in culture, and this outgrowth from the postnatal chromaffin cells is abolished by the corticosteroid dexamethasone. To determine whether adult rat chromaffin cells respond to NGF and dexamethasone, dissociated adrenal medullary cells from 3-month-old rats were cultured for 30 days in the presence or absence of these agents. Such cultures contained typical chromaffin cells, chromaffin cells with processes, and neurons. Fewer than 2 % of normal adult chromaffin cells formed processes under any of the conditions studied, and statistically significant changes in this proportion were not detectable in the presence of NGF or dexamethasone. Adrenal medullary neurons, however, were observed only in the presence of NGF, in cultures with or without dexamethasone, and thus appear to be previously unreported NGF targets which require NGF for survival or process outgrowth. Dexamethasone markedly increased total catecholamine content, total content of epinephrine, and tyrosine hydroxylase activity in cultures with or without NGF. In contrast, postnatal rat chromaffin and rat pheochromocytoma cells which have been studied in culture do not produce epinephrine under any of these conditions. It is concluded that rat adrenal chromaffin cells undergo age-related changes in both structural and functional plasticity. The in vitro characteristics of rat pheochromocytoma cells more closely resemble those of postnatal than of adult rat chromaffin cells, but may not entirely reflect the properties of the majority of chromaffin cells in either age group.
TL;DR: There is no general correlation between the phosphate potential and the mitochondrial respiratory rate in the perfused rat heart, according to calculations of the concentration of free ADP assuming equilibrium in the creatine phosphokinase reaction.
TL;DR: It is concluded that the observed increased activity of the sympathetic nervous system in hypercalcemia could account for the elevation in blood pressure and the enhanced vascular reactivity could explain the hypertension in some patients with primary hyperparathyroidism.
Abstract: To elucidate the pathophysiology of elevated blood pressure in hypercalcemic patients, we studied the plasma concentration of catecholamines and their major metabolites (as an index of sympathetic function) and the blood pressure response to norepinephrine infusion (vascular reactivity) in patients with primary hyperparathyroidism, in patients with primary hypertension, and in normal controls. In addition, we evaluated the hemodynamic response to calcium infusion in normotensive and hypertensive subjects. Plasma levels of both norepinephrine and epinephrine and the metabolites normetanephrine and dihydroxyphenyl-glycol were significantly higher in the hypercalcemic group than in the other two groups. Norepinephrine infusion increased blood pressure by 8.5 +/- 1.4 mm Hg in the control group, by 19 +/- 2 mm Hg in the hypercalcemic group and by 29 +/- 3 mm Hg in the primary hypertensive group. Infusion of calcium produced a significant rise in both systolic and diastolic blood pressures and in peripheral resistance in the hypertensives, whereas in the normotensive group only systolic blood pressure increased, associated with a rise in cardiac output. We conclude that the observed increased activity of the sympathetic nervous system in hypercalcemia could account for the elevation in blood pressure and the enhanced vascular reactivity could explain the hypertension in some patients with primary hyperparathyroidism.
TL;DR: The uptake and excretion of endogenous dopa, dopamine, norepinephrine, and epinephrine by the kidney were studied and the important relationship between renal function and the peripheral sympathetic nervous system was emphasized.
Abstract: The uptake and excretion of endogenous dopa, dopamine, norepinephrine, and epinephrine by the kidney were studied. Blood samples were taken from the aorta at the origin of the renal artery and from the renal vein during a timed urine collection in each of six anesthetised greyhound dogs. Arterial plasma dopa (1,043 +/- 129 pg/ml) and epinephrine (218 +/- 96 pg/ml) were consistently higher than venous levels of dopa (591 +/- 80) and epinephrine (54 +/- 16 pg/ml), showing extraction of these by the kidney, whereas arterial plasma norepinephrine (329 +/- 89 pg/ml) and dopamine (64 +/- 9 pg/ml) were lower than the venous levels of norepinephrine (695 +/- 161 pg/ml) and dopamine (239 +/- 45 pg/ml), indicating secretion of these catecholamines into the circulation. The dopa extracted did not appear in the urine. Norepinephrine (7.2 +/- 1.7 ng/min), epinephrine (4.5 +/- 1.7 ng/min), and dopamine (3.2 +/- 0.7 ng/min) were excreted in the urine. These rates of urinary excretion could be accounted for by glomerular filtration and tubular secretion of the three catecholamines. The kidney extracts circulating dopa. It extracts and excretes epinephrine, norepinephrine, and dopamine, and, in addition, secretes both dopamine and norepinephrine into the circulation. These observations emphasize the important relationship between renal function and the peripheral sympathetic nervous system.