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Results for “Norepinephrine”

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PubMed1996

Developmental characteristics in the daily rhythm of norepinephrine concentration within rabbit brainstem regions.

To examine the development of daily variations in norepinephrine levels, norepinephrine concentrations were measured within five distinct brainstem regions in 3-day-old, 21-day-old, and adult rabbits at 6-h intervals throughout the day. Norepinephrine was measured by radioenzymatic assay, and norepinephrine concentration was expressed relative to wet tissue weight. The data suggest that daily variations for norepinephrine concentrations are established by the third day of life. In the brainstem as a whole, there was an early nocturnal peak (2130 hours) for 3-day-old animals in contrast to a late nocturnal peak (0330 hours) for 21-day-old animals. Adult animals showed a late diurnal (1530 hours) peak. These gross daily variations constitute the sum of distinct region-specific patterns in the development of daily variations in norepinephrine concentration. Norepinephrine is involved in cardiorespiratory regulation and in the regulation of sleep/wake cycles. The observed developmental patterns may relate to the maturation and integration of these physiologic processes.

Animals↗

PubMed1969

Incorporation of 14C-tryptophan into 14C-protein by cultured rat pineals: stimulation by l-norepinephrine.

Organ cultures of individual rat pineals incorporate (14)C-tryptophan into proteins at a nearly constant rate for at least 48 hours. Previous studies have shown that these cultures also convert (14)C-tryptophan to serotonin, melatonin, and 5-hydroxyindoleacetic acid, and release these indoles into the media. The formation of (14)C-protein from (14)C-tryptophan is accelerated by the addition to the culture medium of l-norepinephrine or related catecholamines but is not modified by serotonin, melatonin, or 5-hydroxyindoleacetic acid. One mechanism by which norepinephrine stimulates the synthesis of (14)C-protein from (14)C-tryptophan involves increasing the uptake of the (14)C-tryptophan into pineal parenchymal cells, inasmuch as (1) norepinephrine increases the intracellular content of (14)C-tryptophan as well as its conversion to its major products, (14)C-protein and (14)C-indoles; (2) norepinephrine does not stimulate (14)C-protein synthesis in pineal organs which contain a previously fixed amount of (14)C-tryptophan; and (3) norepinephrine does not stimulate (14)C-protein synthesis from (14)C-methionine or (14)C-leucine. The finding that norepinephrine, but not serotonin, can stimulate the incorporation of (14)C-tryptophan into pineal proteins is consistent with the hypothesis that norepinephrine is the neurotransmitter substance utilized by pineal sympathetic nerve endings.

Aminoisobutyric Acids↗

PubMed1988

Norepinephrine down-regulates the activity of protein S on endothelial cells.

The adrenergic agonist norepinephrine is shown to stimulate endothelium to induce protein S release and degradation, leading to diminished anti-coagulant activity and to down-regulation of protein S cell surface-binding sites. Norepinephrine-induced release of intracellular protein S was blocked by the alpha 1-adrenergic antagonist prazosin (10(-7) M) but not by the alpha-adrenergic antagonist propranolol (10(-6) M) or the alpha 2-adrenergic antagonist yohimbine (10(-5) M) indicating that this response resulted from the specific interaction of norepinephrine with a class of alpha 1-adrenergic receptors not previously observed on endothelium. Attenuation of norepinephrine-induced release of protein S by pertussis toxin in association with the ADP-ribosylation of a 41,000-D membrane protein indicates that this intracellular transduction pathway involves a regulatory G protein. The observation that protein S was released from endothelium in response to maneuvers which elevate intracellular calcium or activate protein kinase C suggests that the response may be mediated via intermediates generated through the hydrolysis of phosphoinositides. Morphologic studies were consistent with a mechanism in which norepinephrine causes exocytosis of vesicles containing protein S. In addition to release of protein S, norepinephrine also induced loss of endothelial cell protein S-binding sites, thereby blocking effective activated protein C-protein S-mediated factor Va inactivation on the cell surface. Norepinephrine-mediated endothelial cell stimulation thus results in loss of intracellular protein S and suppression of cell surface-binding sites, modulating the anti-coagulant protein C pathway on the vessel wall. These studies define a new relationship between an anti-coagulant mechanism and the autonomic nervous system, and indicate a potential role for an heretofore unrecognized class of alpha 1-adrenergic receptors in the regulation of endothelial cell physiology.

Adenosine Diphosphate Ribose↗

PubMed1999

Effects of tramadol stereoisomers on norepinephrine efflux and uptake in the rat locus coeruleus measured by real time voltammetry.

Despite its structural similarity to codeine, tramadol is an unusual analgesic whose antinociceptive efficacy is not solely a result of opioid actions but also of its apparent capacity to block monoamine uptake. Tramadol is a mixture of stereoisomers. In this study, we have examined the actions of racemic, (+)- and (-)-tramadol, in addition to O-desmethyltramadol (the main human metabolite), on electrically evoked norepinephrine efflux and uptake in the locus coeruleus brain slice, measured by fast cyclic voltammetry. Racemic tramadol and its (+)- and (-)-enantiomers (all at 5 mumol litre-1) significantly increased stimulated norepinephrine efflux (P < 0.01) by mean 66 (SEM 10)%, 57 (7)% and 64 (13)%, respectively. However, only (-)-tramadol blocked norepinephrine reuptake (P < 0.01), increasing the reuptake half-time to 499 (63)% of pre-drug values. The metabolite O-desmethyl tramadol was inactive at the concentration tested (5 mumol litre-1). In the case of (-)-tramadol, the effect on norepinephrine efflux was directly proportional to, but significantly smaller than, the effect on norepinephrine uptake (P < 0.01). This appeared to be a result of compensatory alpha 2A autoreceptor tone as the selective alpha 2A autoreceptor antagonist BRL 44408 (1 mumol litre-1) eliminated this difference when its own effects on norepinephrine reuptake were taken into account. The efficacy of (-)-tramadol on norepinephrine uptake, at clinically relevant concentrations, may contribute to its antinociceptive efficacy.

Adrenergic alpha-Antagonists↗

PubMed1980

Effects of calcium ions on the activation of gluconeogenesis by norepinephrine in perfused rat liver.

The effects of calcium ions on the activation of gluconeogenesis by norepinephrine were studied in the perfused rat liver. The norepinephrine-mediated enhancement of gluconeogenesis was accompanied by a transient increase in the reduction level of pyridine nucleotides. There was a positive correlation between the increases in the rate of glucose production and the reduction level of pyridine nucleotides induced by norepinephrine. These changes were "dose-dependent" with respect to the norepinephrine concentration from 5 nM to 1 muM and were mimicked by phenylephrine. The omission of calcium from the perfusate did not modify the basal rate of gluconeogenesis from lactate and pyruvate or the increased rate of glucose production induced by glucagon and isoproterenol. The extents of the responses to norepinephrine and phenylephrine, however, were decreased markedly in liver perfused with a calcium-free medium and/or with phentolamine. Infusion of calcium into the calcium-deficient liver caused an abrupt elevation of glucose production together with a transient reduction of pyridine nucleotides, and the original extent of the response to norepinephrine was recovered. The data presented provide evidence indicating that stimulation of gluconeogenesis by norepinephrine is mediated through an alpha-adrenergic and calcium-dependent mechanism in which redox changes of mitochondrial pyridine nucleotides are involved.

Animals↗

PubMed1998

Isoflurane and sevoflurane augment norepinephrine responses to surgical noxious stimulation in humans.

BACKGROUND: Suppression of hypertensive response to noxious stimulation by volatile anesthetics may be a result of suppression of the stimulation-induced norepinephrine response or that of the cardiovascular response to catecholamines, or both. The suppression of the cardiovascular response is established, but that of norepinephrine response has not been confirmed. The authors hypothesized that the suppression of cardiovascular response but not that of norepinephrine response plays a major role in suppressing the noxious stimulation-induced hypertensive response by volatile anesthetics. METHODS: Forty healthy donors for living-related liver transplantation were allocated to four groups: receiving 1.2% (end-tidal) isoflurane in oxygen and nitrogen, 2.0% isoflurane, 1.7% sevoflurane, or 2.8% sevoflurane. The intraoperative plasma norepinephrine and epinephrine concentrations, arterial blood pressure and pulse rate were measured for the first 15 min of surgery and were compared with the preoperative values. RESULTS: Norepinephrine and epinephrine concentrations both increased intraoperatively in all four groups. The values of maximum increase and area under the concentration-versus-time curve of norepinephrine were greater in the high dose groups of both anesthetics. The intraoperative blood pressure did not differ by different doses of anesthetics, and the degree of increase of blood pressure was not proportional to the plasma catecholamine concentrations. CONCLUSION: The effects of isoflurane and sevoflurane on the surgical noxious stimulation-induced norepinephrine response were inversely proportional to the dose. The suppression of noxious stimulation-induced blood pressure response by anesthetics that were studied may be the result of suppression of the responses of vascular smooth muscle and myocardium to catecholamines.

Adult↗

PubMed2002

Nicotinic acetylcholine receptor regulation of spinal norepinephrine release.

BACKGROUND: Neuronal nicotinic acetylcholine receptor (nAChR) agonists produce antinociception in animals. nAChRs exist almost exclusively on presynaptic terminals in the central nervous system and stimulate neurotransmitter release. This study tested whether nAChR agonists stimulate spinal release of the neurotransmitter norepinephrine either by direct actions on noradrenergic terminals or indirectly by stimulating release of other neurotransmitters to induce norepinephrine release. METHODS: Adult male rats were anesthetized and microdialysis probes inserted in the L2-L4 dermatomes of the spinal cord. Probes were perfused with artificial cerebrospinal fluid containing nicotine, the specific alpha(4)beta(2*) nAChR agonist metanicotine, or nicotine plus nAChR antagonists and norepinephrine measured in the microdialysates. The effects of specific glutamate receptor antagonists and nitric oxide synthase inhibitors were also examined. To determine direct effects on noradrenergic terminals, synaptosomes were prepared from spinal cord and incubated with nAChR agonists and antagonists. RESULTS: Both nicotine and metanicotine induced norepinephrine release in spinal microdialsyates, an effect reduced by nicotinic antagonists but not glutamate antagonists or nitric oxide synthase inhibitors. Both of the nicotinic agonists stimulated norepinephrine release in synaptosomes, and the effect of metanicotine was blocked at lower concentrations of alpha(4)beta(2*)- than alpha(7*)-preferring nAChR antagonists. CONCLUSION: These results suggest that one mechanism by which nAChR agonists act for analgesia is to stimulate spinal norepinephrine release. They do so by actions on alpha(4)beta(2*) nAChRs, and perhaps other subtypes, most likely located on noradrenergic terminals, rather than by indirectly stimulating norepinephrine release through glutamate release or nitric oxide synthesis.

Analgesia↗

PubMed1975

Effect of low dose intra-arterial reserpine on vascular wall norepinephrine content.

A number of reports in recent years have indicated that the administration of low dose intra-arterial reserpine has resulted in significant clinical improvement in patients with symptomatic vasospasm, with the benefits presumably resulting from regional vascular wall norepinephrine depletion with resultant vasodilatation. However, to date, there has been no evidence that such low dose reserpine actually alters vascular wall norepinephrine content. This study was performed to determine both regional and systemic effects of low dose intra-arterial reserpine on vascular-wall norepinephrine content, and the duration of any alterations. Twenty-four mongrel dogs had vascular segments excised and assayed for norepinephrine content, before and for up to 4 weeks following a single injection of reserpine, 0.01 mgm/kg, into one femoral artery. The results indicate a pronounced norepinephrine depletion in the injected femoral arterial system, with the reduction persisting for 2-4 weeks, at which time complete norepinephrine recovery occurred. The visceral vessels sampled also showed considerable norepinephrine depletion, indicating systemic spill-over of the drug from the injected peripheral arterial tree. The visceral vessels, however, showed maximal depletion at 24 hours, with recovery by 7 days.

Animals↗

PubMed1998

Effect of norepinephrine on proliferation, migration, and adhesion of SV-40 transformed human corneal epithelial cells.

PURPOSE: To determine the ability of norepinephrine to modulate proliferation, adhesion, and migration of SV-40 transformed human corneal epithelial cells. METHODS: Assays were performed using SV-40 transformed human corneal epithelial cells. For proliferation assays, cells were plated in 96-well plates coated with fibronectin and collagen (FNC). A dose-response curve was generated for norepinephrine in concentrations of 100 nM-100 microM. The cell number in each well was evaluated using the fluorochrome Calcein AM (an intracellular esterase cleavage substrate), and fluorescence was determined using an automated fluorescent plate reader. For cell adhesion, 25 x 10(-3) cells were plated onto FNC-coated 96-well plates, incubated in 10 nM-100 microM norepinephrine for 90 min, gently irrigated, and the remaining adherent cells quantitated. Cell migration was measured using blind-well migration chambers with a 10-microm pore size and FNC-coated filters. Cells (250 x 10(3)) were added to the upper chamber, incubated for 18 h in the presence of factors, after which time the cells that had migrated through the filter were quantitated. The toxicity of norepinephrine was evaluated using a standard Live/Dead assay employing the combined fluorochromes of ethidium homodimer (to indicate dead cells) and Calcein AM (to indicate viable cells). Varying concentrations of norepinephrine were added, and the cells incubated for 3 h and the fluorometric assay performed. RESULTS: Norepinephrine stimulated corneal epithelial cell proliferation and migration over a wide range of concentrations. It did not modulate cell adhesion and demonstrated cell toxicity only at the highest (supraphysiologic) concentration tested. CONCLUSIONS: Norepinephrine is normally found in the cornea and may be important in the maintenance of normal corneal homeostasis and in wound-healing processes.

Antigens, Polyomavirus Transforming↗

PubMed1994

Effects of dobutamine and norepinephrine on oxygen availability in tamponade-induced stagnant hypoxia: a prospective, randomized, controlled study.

OBJECTIVES: To explore the effects of dobutamine and norepinephrine on the global cardiovascular response and on the relationship between oxygen uptake (VO2) and oxygen delivery (DO2) during an acute reduction in blood flow associated with tamponade. DESIGN: Prospective, randomized, controlled acute intervention study. SETTING: University intensive care unit (ICU) laboratory. SUBJECTS: Twenty healthy, anesthetized mongrel dogs, weighing 19 to 28 kg. INTERVENTIONS: Six dogs served as control, seven dogs were given 10 micrograms/kg/min of dobutamine and another seven dogs were given 1 microgram/kg/min of norepinephrine. Data were collected at graded incremental levels of intrapericardial pressure. MEASUREMENTS AND MAIN RESULTS: VO2 was derived from expired gas analysis and DO2 was calculated from the product of thermodilution cardiac index and arterial oxygen content. In each animal, two catheters were inserted into the pericardium to induce tamponade by saline infusion and to measure the intrapericardial pressure. The critical Do2 value, below which VO2 decreased, was found at 9.4 +/- 1.3 mL/kg/min in the control animals. When DO2 decreased to below this critical value, lactic acidosis developed. Dobutamine and norepinephrine, at the dose that was administered, significantly increased cardiac index and DO2. Critical DO2 was slightly higher in the treated than in the control animals (12.1 +/- 1.6 mL/kg/min in dobutamine and 13.2 +/- 0.9 mL/kg/min in norepinephrine, NS). VO2 at critical DO2 was significantly higher in the treated groups than in the control group (7.7 +/- 1.1 mL/kg/min in the dobutamine group and 7.9 +/- 0.9 mL/kg/min in the norepinephrine group vs. 5.4 +/- 0.4 mL/kg/min in control, both p < .01). There was no significant difference in the critical oxygen extraction ratio and the slope of the supply-dependent line between the three groups. In dobutamine-treated animals, cardiac index, DO2, and VO2 were better maintained for any intrapericardial pressure than in the other groups. Critical intrapericardial pressure, at which VO2 started to decrease, was significantly higher in the dobutamine-treated group than in the control group (13.8 +/- 2.3 vs. 9.3 +/- 1.2 mm Hg, p < .05). At critical DO2, the mean blood lactate concentration was also lower in the dobutamine-treated animals than in the other animals (2.1 +/- 0.3 vs. 4.1 +/- 0.7 mmol/L in control and 3.8 +/- 0.4 mmol/L in the norepinephrine group, both p < .05). CONCLUSIONS: During low-flow states associated with tamponade, both dobutamine and norepinephrine at the dose used increased cardiac index, DO2, and VO2, but dobutamine delayed the onset of tissue hypoxia by further increasing blood flow and oxygen availability. In the conditions of the present study, neither agent significantly influenced the oxygen extraction capabilities of the body.

Animals↗

PubMed2002

Effect of increasing norepinephrine dosage on regional blood flow in a porcine model of endotoxin shock.

OBJECTIVE: To evaluate the effect of a norepinephrine-induced differential increase in mean arterial pressure on splanchnic and renal perfusion in a porcine model of volume-resuscitated endotoxic shock. DESIGN: Prospective, controlled, acute interventional study. SETTING: Animal research laboratory. SUBJECTS: Fourteen landrace pigs, seven treated with norepinephrine and seven used as endotoxemic controls. INTERVENTIONS: In an acute endotoxic shock model, norepinephrine was used to reverse hypotension in seven fluid-resuscitated pigs, anesthetized with alpha-chloralose and equipped with flow probes around the portal vein and renal artery, renal and jejunal mucosal laser Doppler flowmetry, and jejunal tonometry. Mean arterial pressure was increased by 10 and then 20 mm Hg above the shock level with norepinephrine. Seven shocked, fluid-resuscitated only animals served as the comparison group. MEASUREMENTS AND MAIN RESULTS: Measurements were performed before 2-hr endotoxin infusion and at the end of each increased level of mean arterial pressure. Raising mean arterial pressure with norepinephrine by 10 mm Hg significantly increased cardiac output, systemic oxygen extraction, and portal vein blood flow; stabilized metabolic acidosis; and tended to restore renal and jejunal mucosal flows to preshock levels. Increasing mean arterial pressure by 20 mm Hg further increased cardiac output and oxygen delivery but without improving portal vein, renal artery, and jejunal mucosal blood flows. CONCLUSIONS: Norepinephrine, administered to increase mean arterial pressure by 10 mm Hg in an acute model of volume-resuscitated endotoxic shock, improved systemic and regional perfusion. The administration of norepinephrine to increase mean arterial pressure 20 mm Hg above shock did not increase renal and splanchnic blood flows, despite an enhanced cardiac output.

Animals↗

PubMed1988

Aortic pulsatile pressure and diameter response to intravenous perfusions of angiotensin, norepinephrine, and epinephrine in conscious dogs.

The aortic elastic behavior has been studied in conscious dogs chronically instrumented with a pressure microtransducer and two ultrasonic crystals. Pressure and diameter measurements were analyzed in terms of their mean values and systolic-diastolic variations, enabling calculation of Peterson elastic modulus, and were displayed in the x-y form to obtain pressure diameter hysteresis loops. After recovery from surgery and under autonomic blockade, intravenous perfusions of angiotensin, norepinephrine, and epinephrine were made at incremental steps of doses until steady-state pressure-diameter changes were achieved. The slopes of the positive pressure-diameter correlations obtained at each dose of the same vasoactive substance were higher for angiotensin than norepinephrine (p less than 0.01) and epinephrine (p less than 0.001) and were higher for norepinephrine than epinephrine (p less than 0.05). Similarly, the slopes of the elastic modulus to mean pressure relation were significantly lower for angiotensin than for norepinephrine (p less than 0.05) and epinephrine (p less than 0.001) and were significantly lower for norepinephrine than epinephrine (p less than 0.001). Thus, at the same transmural pressure, the distension and stiffness of the aorta were lower and higher with epinephrine than with norepinephrine, respectively, and with norepinephrine than with angiotensin suggesting different potencies of these drugs in terms of smooth muscle activation in the aorta.

Angiotensin II↗

PubMed1998

Differences in responses to norepinephrine and adenosine triphosphate in isolated, perfused mesenteric vascular beds between normotensive and spontaneously hypertensive rats.

The responses to norepinephrine and adenosine 5' triphosphate (ATP) of isolated, perfused mesenteric vascular beds were compared between spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. Norepinephrine (0.01-100 nmol) dose-dependently increased perfusion pressure in the intact bed and the arteries, but not in the veins. The maximal responses in SHRs were larger than those in WKY rats. ATP (0.1-3,000 nmol) increased perfusion pressure in all preparations. The responses of the intact bed and the veins were larger in SHRs, whereas there was no strain difference in the arteries. Indomethacin (5 x 10(-6) M) enlarged the norepinephrine responses of both strains only in the intact beds and did not affect the ATP responses, except the veins in SHRs, where it was reduced. N(G)-nitro-L-arginine methyl ester (5 x 10(-6) M), in combination with indomethacin, potentiated the responses, except the arterial response to high doses of norepinephrine in SHRs, which was not affected. Endothelium denudation in the arteries produced similar changes to those after the combined treatment. UK14,304-induced and ADPbetaS-induced decreases in perfusion pressure at increased tone were similar between the strains. Thus neither the vasodilation induced by the stimulation of alpha2-adrenoceptors nor of P2y receptors seems to affect the response to norepinephrine or to ATP, respectively. These results demonstrate that the intact mesenteric vascular bed of SHRs shows potentiated responses not only to norepinephrine, but also to ATP, as compared with WKY rats, and that the critical regions for determining the strain differences for norepinephrine are overall arteries, and that for ATP are the vessels downstream from arterioles. In the intact beds, neither regulation by endogenous prostanoids nor that by endothelium-derived relaxing factors (EDRFs) is implicated in the strain difference. However, these two types of regulation differ markedly between different kinds of vessels.

Adenosine Triphosphate↗

PubMed2003

Presynaptic regulation of norepinephrine release in a model of nonfailing hypertrophied myocardium.

Dysregulation of cardiac norepinephrine release in heart failure has been linked to an impairment of presynaptic regulation. Although myocardial hypertrophy is a key finding in the development of heart failure, there are no data available regarding prejunctional modulation of sympathetic transmitter release in nonfailing hypertrophied myocardium. This study investigated norepinephrine release, induced by electrical field stimulation, in isolated rat hearts obtained from animals pretreated by suprarenal aortic banding (AB) or sham operation. Seven weeks following operation, substantial myocardial hypertrophy was observed in AB rats without evidence of cardiac decompensation. Cardiac norepinephrine release was negatively correlated with heart weight/body weight ratio in rats with AB. No such correlation was found in sham rats. Function of presynaptic alpha(2)-adrenoceptors and AT(1) receptors was tested utilizing specific receptor agonists and antagonists. UK 14,304 (alpha(2)-adrenoceptor stimulation) suppressed norepinephrine release in sham and AB hearts without difference between the groups. Conversely, rauwolscine (alpha(2)-adrenoceptor blockade) enhanced norepinephrine release in sham and AB hearts. Again, no difference between the groups was observed. The same was true for stimulation and blockade of AT(1) receptors with angiotensin II and candesartan. Presynaptic modulation of norepinephrine release via alpha(2)-adrenoceptors and AT(1) receptors is functional in nonfailing hypertrophied myocardium. Reduced norepinephrine release in hypertrophy may therefore indicate structural rather than functional alterations.

Animals↗

PubMed2005

Effects of dopamine and norepinephrine on systemic and hepatosplanchnic hemodynamics, oxygen exchange, and energy balance in vasoplegic septic patients.

Dopamine is widely used to improve systemic and hepatosplanchnic hemodynamics and oxygenation during sepsis. However, some studies have suggest that norepinephrine may have beneficial effects on regional blood flow and metabolism, whereas dopamine might have deleterious effects related to redistribution of blood flow away from the intestinal mucosa or by decreasing directly the cell redox state. In 12 vasoplegic septic patients, we compared the effects of norepinephrine and dopamine on systemic and hepatosplanchnic hemodynamics, oxygenation, and energy metabolism. Catecholamines were administered in a crossover randomized order to maintain mean arterial pressure (MAP) at 80 mmHg. Hepatosplanchnic blood flow (Qspl) was determined using a continuous infusion of indocyanine green dye. Despite a similar MAP, the cardiac index was higher with dopamine than with norepinephrine (6.3 [5.3-7.3] vs. 4.3 [3.8-4.9] L.min.m) (P <0.001). Qspl was similar with both catecholamines, but the ratio of Qspl to cardiac output was significantly lower with dopamine (23.9% [17.5-33.5]) than with norepinephrine (33.5% [25.8-37]) (P <0.05). Although global O2 delivery and O2 consumption were higher with dopamine (782 [707-859] vs. 553 [512-629] mL.min.m, P <0.001 and 164 [134-192] vs. 128 [111-149] mL.min.m, P <0.001, respectively), hepatosplanchnic O2 delivery and consumption were not different. Hepatic lactate uptake was lower (0.47 [0.3-0.89] vs. 1.01 [0.69-1.34] mmol.min) (P <0.01), and hepatic venous lactate-to-pyruvate ratio was higher (15.3 [7.6-21.1] vs. 11.2 [6.6-15.1], P <0.05) with dopamine than with norepinephrine. In vasoplegic septic patients, maintaining mean arterial pressure, hepatosplanchnic hemodynamics, and oxygen exchange with dopamine requires a consequent increased cardiac output, which is responsible for an increased global oxygen demand when compared with norepinephrine. In addition, dopamine impairs the hepatic energy balance. Its position as a preferential treatment compared with norepinephrine in this context may therefore be questionable.

Adult↗

PubMed2006

Norepinephrine modulates the inflammatory and proliferative phases of wound healing.

BACKGROUND: Injury results in the massive release of norepinephrine (NE) into the peripheral circulation. Recent investigations have demonstrated functional adrenoreceptors on the cellular mediators of cutaneous wound healing and NE-induced phenotypic alterations in immune cells have been demonstrated in vitro. Despite this, there is little description of how NE might alter the phases of wound healing in vivo. The purpose of this study was to compare cutaneous wound healing in norepinephrine-intact and norepinephrine-depleted mice. METHODS: Norepinephrine-depleted (NED) mice were generated by chemical axotomy with 6-hydroxydopamine and compared with norepinephrine-intact (NEI) animals (n = 6-12 per group, per time point). Using an excisional wound model, neutrophil recruitment was measured by myeloperoxidase assay. Macrophage recruitment and angiogenesis were measured by immunohistochemistry and re-epithelialization was determined histologically. The development of incisional wound disruption strength was determined over time. Finally, macrophage scavenger function was assessed by an in vitro latex bead phagocytosis assay. RESULTS: Wounds from NEI mice demonstrated greater neutrophil infiltration than NED wounds (24, 72 hours; p < 0.05). Wound macrophage recruitment was initially higher in NEI animals (24 hours, p < 0.05), but was eventually surpassed by that of NED animals (120 hours, p < 0.05). Angiogenesis was decreased while re-epithelialization was accelerated in NEI animals (p < 0.05). Wound disruption strength and macrophage scavenger function were unaltered between NED and NEI mice. CONCLUSIONS: Norepinephrine modulates the inflammatory and proliferative phases of wound healing in a temporally defined, cell-specific manner. By increasing recruitment of innate immune cells and expediting wound closure, norepinephrine appears to play a protective role in defense against infection.

Animals↗

PubMed1979

Norepinephrine-stimulated fatty-acid release and oxygen consumption in isolated hamster brown-fat cells. Influence of buffers, albumin, insulin and mitochondrial inhibitors.

Brown fat cells isolated from adult golden hamsters have earlier been found to respond to addition of the physiological agonist norepinephrine with an increased rate of oxygen consumption and with fatty acid release. Working with these cells, we found the following. 1. The presence of albumin in the incubation medium (phosphate buffer) increases norepinephrine-induced fatty acid release and tends to stabilize the rate of oxygen consumption; bubbling of phosphate buffer with 5% CO2 in air has only a slight effect on fatty acid release. 2. In the presence of albumin, the norepinephrine-induced rate of oxygen consumption is also stable in bicarbonate buffer; it is higher than in the phosphate + CO2 buffer and the brown fat cells have a higher sensitivity to norepinephrine. 3. 20 mM phosphate (as e.g. present in a phosphate buffer) inhibits both fatty acid release and oxygen consumption. 4. Insulin inhibits the rate of oxygen consumption, but only at suboptimal concentrations of norepinephrine. 5. Atractylate inhibits submaximal norepinephrine-induced respiration, indicating that some oxidative phosphorylation takes place in norepinephrine-stimulated brown fat cells. 6. Fatty acid export from brown fat should be regarded as physiologically important.

Adipose Tissue, Brown↗

PubMed1986

Stimulatory effect of ascorbic acid on norepinephrine biosynthesis in digitonin-permeabilized adrenal medullary chromaffin cells.

The regulatory role of ascorbic acid in norepinephrine biosynthesis was studied using digitonin-permeabilized chromaffin cells. When permeabilized chromaffin cells were incubated with [3H]3,4-dihydroxyphenylethylamine ([3H]dopamine) in calcium-free medium, the amounts of radioactive dopamine and norepinephrine measured in the cell fraction were increased as a function of incubation time and dopamine concentration. Both the accumulation of dopamine and the formation of norepinephrine were shown to require the presence of Mg-ATP in the medium. These results indicate that the permeabilization of chromaffin cells by digitonin treatment does not disrupt the functions of chromaffin granules, including dopamine uptake, norepinephrine formation, and storage of these amines. Using this permeabilized cell system, the effect of ascorbic acid on the rates of dopamine uptake and hydroxylation was investigated. The formation of norepinephrine was stimulated by ascorbic acid at concentrations of 0.5-2 mM in the presence of Mg-ATP. By contrast, dopamine uptake was not affected by the presence or absence of ascorbic acid in the medium. These findings provide evidence that ascorbic acid may stimulate the conversion of dopamine to norepinephrine by increasing dopamine beta monooxygenase activity rather than by increasing the substrate supply of dopamine. These observations also suggest that the rate of norepinephrine biosynthesis in adrenal medullary cells may be regulated by the concentration of ascorbic acid within the cell cytoplasm.

Adenosine Triphosphate↗