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PubMed1999

Genetic approaches to studying norepinephrine function: knockout of the mouse norepinephrine transporter gene.

Norepinephrine is an important chemical messenger in the nervous system. It regulates affective states, learning and memory, endocrine and autonomic functions. It has been implicated in depression, aggression, and addiction, as well as cardiac and thermal dysregulation. The norepinephrine transporter functions by uptaking norepinephrine back into the cell for cyclic use, and is a direct target of a number of antidepressants and psychostimulants. Functional deletion (knockout) of monamine transporters results in increases in extracellular levels of neurotransmitters, thereby prolonging their actions. For the norepinephrine transporter knockout mice, this altered state of the norepinephrine system should simulate the therapeutic effects of norepinephrine selective antidepressants and some of the effects of psychostimulants. Careful use of such an animal model can hopefully provide valuable insight into the multiple roles norepinephrine plays in normal and pathological physiology.

Animals↗
PubMed1989

Direct evidence that an increase in aortic norepinephrine level in response to insulin-induced hypoglycemia is due to increased adrenal norepinephrine output.

This study reports on the major source of circulating norepinephrine that is known to increase, progressively, during sustained hypoglycemia induced by intravenous insulin administration. Plasma concentrations of epinephrine, norepinephrine, and dopamine were simultaneously determined for adrenal venous and aortic blood in dogs anesthetized with sodium pentobarbital. The model used allowed us to perform a functional adrenalectomy (ADRX), while continuously monitoring the adrenal medullary secretory function. Under basal conditions, the net output (micrograms/min) of adrenal epinephrine, norepinephrine, and dopamine were 0.169 +/- 0.074, 0.067 +/- 0.023, and 0.011 +/- 0.003, respectively. Plasma concentrations (ng/mL) of aortic epinephrine, norepinephrine, and dopamine were 0.132 +/- 0.047, 0.268 +/- 0.034, and 0.034 +/- 0.009. Following insulin injection (0.15 IU/kg, i.v.), the net output (micrograms/min) of adrenal epinephrine, norepinephrine, and dopamine increased gradually (p less than 0.05), reaching the values of 0.918 +/- 0.200, 0.365 +/- 0.058, and 0.034 +/- 0.007 30 min after insulin administration. Similarly, aortic epinephrine, norepinephrine, and dopamine concentrations (ng/mL) increased significantly (p less than 0.05) to 0.702 +/- 0.144, 0.526 +/- 0.093, and 0.066 +/- 0.024. The aortic glucose concentration (mg/dL) was diminished from 81.8 +/- 4.1 to 36.9 +/- 3.4 (p less than 0.01). After taking the blood sample at 30 min following insulin administration, ADRX was immediately performed. Five minutes after the onset of ADRX, the net output (micrograms/min) of adrenal epinephrine, norepinephrine, and dopamine increased further to 1.707 +/- 0.374 (p less than 0.05), 0.668 +/- 0.139 (p less than 0.05), and 0.052 +/- 0.017.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1971

Human norepinephrine metabolism. Its evaluation bydministration of tritiated norepinephrine.

It has become increasingly apparent that evaluation of human norepinephrine metabolism simply by assay of catecholamines in urine is inadequate for differentiation of many physiological or pathological states. In an attempt to examine norepinepherine metabolism in the human subject, tritium-labeled d,l-norepinephrine was administered to 11 normal adults and the definitive turnover rates and relative specific activities of norepinephrine and its major catabolites, vanillylmandelic acid, 3-methoxy-4-hydroxyphenylethyleneglycol, and normetanephrine, as well as the cumulative 24 hr isotope excretion were determined. The major endogenous norepinephrine catabolites were also quantitatively assayed. In order to verify the reliability of the isotope label, parallel studies were carried out in two patients to whom norepinephrine-(14)C was administered. Metabolic studies were repeated after the administration of reserpine to gain further insight into the distribution of the label.All studies demonstrated a consistent difference between the relative specific activities of the amines and their deaminated congeners, thereby indicating an uneven distribution of the labeled material. The marked decrease in the relative specific activities of the deaminated catabolites after the administration of reserpine showed that the present experimental technique succeeded in labeling, though to a limited extent, the storage or reserpine-releasable pool. A dose of reserpine known to interfere with sympathetic activity but failing to elicit a change in excretion of endogenous catecholamine catabolites, nonetheless resulted in a marked abnormality in the metabolic handling of labeled norepinephrine. It is anticipated that such studies may not only be of value in measuring sympathetic activity in the intact human subject during physiologic variations and pathologic states associated with abnormalities in catecholamine metabolism, but may serve as a technique whereby drugs that affect human norepinephrine metabolism may undergo precise pharmacologic evaluation.

Adolescent↗
PubMed1993

The differential effects of circulating norepinephrine and neuronally released norepinephrine on sodium excretion in humans.

The renal effects of incremental infusions of norepinephrine (placebo, 0.025 mu/kg/min), 0.075 micrograms/kg/min, phenylephrine (placebo, 0.5 micrograms/kg/min, 2.5 micrograms/kg/min), and tyramine (placebo, 2 micrograms/kg/min, 15 micrograms/kg/min) were examined in three respective groups (n = 9, 8, and 8) of normotensive male subjects undergoing water diuresis. Tyramine is an indirect sympathetic agent that causes neuronal release of endogenous norepinephrine. Increases in mean arterial pressure during each high-dose infusion were comparable in all three groups. Both norepinephrine and phenylephrine caused a decrease in urinary sodium excretion and effective renal plasma flow, with no changes in glomerular filtration rate. Proximal tubular sodium reabsorption, as assessed by both lithium clearance and solute-free water clearance methods, was increased by pressor doses of norepinephrine and phenylephrine. In contrast, a similar pressor dose of tyramine was associated with a pressure natriuresis, an increase in effective renal plasma flow, and a decrease in proximal tubular sodium reabsorption. Our data indicate that, in normotensive humans, circulating catecholamines (norepinephrine and phenylephrine) have opposite effects on renal sodium handling from neuronally released norepinephrine (tyramine).

Adult↗
PubMed1993

Real-time monitoring of electrically stimulated norepinephrine release in rat thalamus: II. Modeling of release and reuptake characteristics of stimulated norepinephrine overflow.

As in the preceding study, electrical stimulation was used to effect release overflow of norepinephrine in the rat thalamus. Using a weak electrochemical pretreatment of a carbon fiber electrode, it was possible to "tune in" the electrochemical response signal for norepinephrine without metabolite interference. This reasonably selective signal was then used to study the degradation of norepinephrine release ability caused by prolonged stimulation. Further, the signals were modeled by the method used successfully for stimulated dopamine overflow, providing hitherto unavailable information on the temporal and spatial characteristics of norepinephrine release overflow. Pertinent comparisons between the release characteristics of the dopamine and norepinephrine systems show that the half-life for norepinephrine in the extracellular fluid space is approximately 1 s in thalamus compared with 33 ms for dopamine in caudate.

Animals↗
PubMed1991

Effect of norepinephrine on myocardial collagen gene expression and response of cardiac fibroblasts after norepinephrine treatment.

Biosynthesis of the collagen matrix of the heart has been shown to be regulated under various physiologic and pathologic conditions. Biogenic amines have known effects on myocardial function. The authors studied the effects of norepinephrine on myocardial collagen gene expression in the rat heart. Norepinephrine was administered intravenously in a sustained-release manner. Within 1 hour after treatment, the abundance of mRNA for pro alpha 2 (I) collagen increased by 212% (P = 0.05), TGF-beta 1 by 91% (P = 0.05), and cytoskeletal actin by 429% (P less than 0.01) in the ventricular myocardium of the treated rats compared with that in control untreated rats. In extended period of treatment, the abundance of mRNA for pro alpha 2 (I) collagen reached a peak (206% increase, P less than 0.01) at day 3, remained elevated through day 6, and returned to the control levels at 2 weeks after treatment. The expression of mRNA for TGF-beta 1 was coregulated with that of pro alpha 2 (I) collagen. The abundance of mRNA for cytoskeletal actin showed a sharp increase (323%, P less than 0.05) at day 1 and remained elevated through day 6 in treated hearts compared with that in control hearts and returned to the control levels at 2 weeks after treatment. Coadministration of alpha-receptor blocker, phentolamine, led to modest reversal, whereas coadministration of beta-receptor blocker, propranolol, led to about 50% reversal of norepinephrine effects on the abundance of mRNAs. At day 3 of treatment, collagen content of ventricular tissue, as determined by hydroxyproline measurement was increased by 13% (P less than 0.05) in treated hearts. Immunofluorescent light microscopy showed increased collagen deposition and focal areas of necrosis in the endocardial regions in hearts of animals treated with norepinephrine for 2 weeks. In vitro studies on cultured cardiac fibroblasts showed that although norepinephrine treatment does not lead to significant changes in the abundance of mRNA for pro alpha 2 (I) collagen, it leads to increased mRNA for cytoskeletal actin and increased (113%, P less than 0.05) 3H-thymidine incorporation into the cell nuclei of treated cells compared with that in untreated cells. The authors conclude that although norepinephrine has no direct in vitro effects on collagen type I biosynthesis, its in vivo effects may lead to a cascade of events such as induction of growth factors that ultimately result in increased expression of collagen type I in the myocardium.

Actins↗
PubMed2006

Norepinephrine acts as D1-dopaminergic agonist in the embryonic avian retina: late expression of beta1-adrenergic receptor shifts norepinephrine specificity in the adult tissue.

Dopamine is the main catecholamine found in the chick retina whereas norepinephrine is only found in trace amounts. We compared the effectiveness of dopamine and norepinephrine in promoting cyclic AMP accumulation in retinas at embryonic day 13 (E13) and from post-hatched chicken (P15). Dopamine (EC(50)=10microM) and norepinephrine (EC(50)=30microM), but not the beta(1)-adrenergic agonist isoproterenol, stimulated over seven-fold the production of cyclic AMP in E13 retina. The cyclic AMP accumulation induced by both catecholamines in embryonic tissue was entirely blocked by 2microM SCH23390, a D(1) receptor antagonist, but not by alprenolol (beta-adrenoceptor antagonist). In P15 retinas, 100microM isoproterenol stimulated five-fold the accumulation of cAMP. This effect was blocked by propanolol (10microM), but not by 2microM SCH23390. Embryonic and adult retina display beta(1) adrenergic receptor mRNA as detected by RT-PCR, but the beta(1) adrenergic receptor protein was detected only in post-hatched tissue. We conclude that norepinephrine cross-reacts with D(1) dopaminergic receptor with affinity similar to that of dopamine in the embryonic retina. In the mature retina, however, D(1) receptors become restricted to activation by dopamine. Moreover, as opposed to the embryonic tissue, norepinephrine seems to stimulate cAMP accumulation via beta(1)-like adrenergic receptors in the mature tissue.

Animals↗
PubMed2003

Antagonism of the stress-induced increase in cortical norepinephrine output by the selective norepinephrine reuptake inhibitor reboxetine.

We have previously shown that long-term treatment of rats with antidepressant drugs that affect the activity of noradrenergic and serotonergic neurons by different mechanisms, inhibits the increase in cortical norepinephrine output induced by stress. With the use of microdialysis, we have now evaluated the effects of reboxetine, an antidepressant drug that selectively inhibits norepinephrine reuptake, on the increase in cortical norepinephrine output elicited in rats by exposure to foot-shock stress or by the acute administration of N-methyl-beta-carboline-3-carboxamide (FG 7142) (20 mg/kg, i.p.). Foot-shock stress and FG 7142 each induced a marked increase in the cortical extracellular concentration of norepinephrine (+200 and +90%, respectively) in control rats. Long-term treatment with reboxetine (10 mg/kg, i.p., once a day for 21 days) reduced the effect of foot-shock stress and completely antagonized the effect of FG 7142 on cortical norepinephrine output. Our results suggest that changes in the activity of noradrenergic neurons in the cortex might be relevant to the anxiolytic and antidepressant effects of reboxetine.

Adrenergic Uptake Inhibitors↗
PubMed1988

The depletion of rat cortical norepinephrine and the inhibition of [3H]norepinephrine uptake by xylamine does not require monoamine oxidase activity.

Inhibition of monoamine oxidase A through pretreatment of rats with clorgyline (10 mg/kg ip) or the pro-drug MDL 72,394 (0.5 mg/kg ip) did not block the amine-depleting action of xylamine (25 mg/kg ip). Xylamine treatment resulted in a loss of approximately 60% of the control level of norepinephrine in the cerebral cortex. A 1-hr pretreatment, but not a 24-hr pretreatment, with the monoamine oxidase B inhibitor, L-deprenyl (10 mg/kg ip), prevented the depletion of norepinephrine by xylamine. In addition, pretreatment with MDL 72,974 (1.25 mg/kg ip), a monoamine oxidase B inhibitor without amine-releasing or uptake - inhibiting effects, did not protect cortical norepinephrine levels. Inhibition of monoamine oxidase by either MDL 72,974 or MDL 72,394 did not prevent the inhibition of [3H]norepinephrine uptake into rat cortical synaptosomes by xylamine. These data indicate that monoamine oxidase does not mediate the amine-releasing or uptake inhibiting properties of xylamine. The protection afforded by L-deprenyl following a 1-hr pretreatment most probably was due to accumulation of its metabolite, L-amphetamine, which would inhibit the uptake carrier. A functional carrier is required for depletion since desipramine (20 mg/kg ip) administered 1 hr prior to xylamine, was also able to prevent depletion of norepinephrine.

Allyl Compounds↗
PubMed1987

Effects of insulin and norepinephrine on glucose transport and metabolism in rat brown adipocytes. Potentiation by insulin of norepinephrine-induced glucose oxidation.

Glucose is an important fuel for rat brown adipose tissue in vivo and its utilization is highly sensitive to insulin. In this study, the different glucose metabolic pathways and their regulation by insulin and norepinephrine were examined in isolated rat brown adipocytes, using [6-14C]glucose as a tracer. Glucose utilization was stimulated for insulin concentrations in the range of 40-1000 microU/ml. Furthermore, the addition of adenosine deaminase (200 mU/ml) or adenosine (10 microM) did not alter insulin sensitivity of glucose metabolism. The major effect of insulin (1 mU/ml) was a respective 7-fold and 5-fold stimulation of lipogenesis and lactate synthesis, whereas glucose oxidation remained very low. The 5-fold stimulation of total glucose metabolism by 1 mU/ml of insulin was accompanied by an 8-fold increase in glucose transport. In the presence of norepinephrine (8 microM), total glucose metabolism was increased 2-fold. This was linked to a 7-fold increase of glucose oxidation, whereas lipogenesis was greatly inhibited (by 72%). In addition, norepinephrine alone did not modify glucose transport. The addition of insulin to adipocytes incubated with norepinephrine, induced a potentiation of glucose oxidation, while lipogenesis remained very low. In conclusion, in the presence of insulin and norepinephrine glucose is a oxidative substrate for brown adipose tissue. However the quantitative importance of glucose as oxidative fuel remains to be determined.

Adipose Tissue, Brown↗
PubMed1992

Norepinephrine-containing glomus cells in the rabbit carotid body. I. Autoradiographic and morphometric study after tritiated norepinephrine uptake.

Rabbit carotid bodies were investigated by autoradiography at both the light and electron microscope levels following tritiated norepinephrine administration either in vivo or in vitro. Two kinds of labelled structures were found: nerve fibres (absent in sympathectomized carotid bodies) and some type I glomus cells. Desipramine (a specific norepinephrine uptake inhibitor) prevented labelling. Most of the labelled cells differed from unlabelled ones by the presence of (i) large dense-cored vesicles characterized by a large halo between the membrane and an eccentric dense core; (ii) a nucleus showing a more electron dense chromatin and a more irregular shape; and (iii) relatively abundant glycogen particles. A new weakly-labelled cells were characterized by a pyknotic nucleus and very swollen dense-cored vesicles, and were presumed to be degenerating. Dense core diameters of dense-cored vesicles were distributed according to a unimodal distribution in labelled cells as in unlabelled ones but with an extension towards both large and very small diameters in labelled cells. The mean diameter was higher in labelled cells than in unlabelled ones (127 nm versus 113 nm, P less than 0.01). The labelling intensity (as estimated by the number of silver grains per unit of cytoplasmic area) was maximum in cells having dense-cored vesicles whose mean diameter was between 130 and 170 nm, but decreased for cells with mean diameter of dense cores smaller than 130 nm, or larger than 170 nm. Thus, in the rabbit carotid body, some glomus cells differ from others by their ability to take up tritiated norepinephrine and by the presence of larger dense-cored vesicles. However, this distinction is not clearcut and there are many intermediates. The observations suggest a phenomenon of evolution deriving from a unique cell type and typified by both metabolic norepinephrine uptake ability, glycogen accumulation) and morphologic changes (increase in diameter of dense-cored vesicles). It seems, therefore, more appropriate to consider these results in terms of different functional states rather than different types of glomus cells.

Animals↗
PubMed1979

Diagnosis and localization of pheochromocytoma. Detection by measurement of urinary norepinephrine excretion during sleep, plasma norepinephrine concentration and computerized axial tomography (CT-scan).

The feasibility of differentiating patients with pheochromocytoma from other hypertensive patients by measuring urinary excretion rates of norepinephrine during sleep, a period of physiologic suppression of norepinephrine release, was investigated. The mean excretion rates of norepinephrine in 248 normal subjects and in 109 patients with essential hypertension were 1.03 +/- 0.03 and 1.12 +/- 0.06 (SEM) micrograms/hour, respectively, whereas the lowest excretion rate among the six patients with pheochromocytoma was about seven times higher. Plasma norepinephrine concentration in patients with pheochromocytoma was also consistently above the range observed in both normotensive and hypertensive subjects. CT scan correctly identified the same tumors visualized by selective arteriography. It is suggested that the usefulness of these approaches will provide simpler means of screening and detecting pheochromocytoma.

Adolescent↗
PubMed1990

Effect of a synthetic norepinephrine precursor, L-threo-3,4- dihydroxyphenylserine on the total norepinephrine concentration in the cerebrospinal fluid of parkinsonian patients.

We studied the effect of a synthetic norepinephrine precursor, L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on the total (conjugated and unconjugated) norepinephrine concentrations in the cerebrospinal fluid (CSF) of 6 parkinsonian patients with freezing phenomenon. The total norepinephrine concentrations in the CSF increased from 5- to 75-fold after treatment with L-threo-DOPS. The degree of increase in the norepinephrine (NE) concentrations was closely correlated to the dosage of L-threo-DOPS. The freezing phenomenon improved in 3 out of 6 patients.

Carbidopa↗
PubMed1990

Phorbol Ester Interferes with [3H]Norepinephrine Accumulation into Monolayers of PC 12 Cells by Stimulating the Release of Endogenous Norepinephrine.

In this study we have observed an inhibition of the [3H]norepinephrine ([3H]NE) accumulation into rat phaeochromocytoma PC 12 cells by phorbol 12-myristate 13-acetate (PMA), whereas a biologically inactive phorbol ester was without effect. The inhibition was no longer observed when the PC 12 cells were preincubated with 10 microM reserpine, which inhibits the uptake of norepinephrine into the storage vesicles. This suggested a role of the intact vesicles in the inhibitory phenomenon. Subsequently we could show that PMA increased the efflux of [3H]NE from PC 12 cells in a dose dependent manner. It seemed likely, therefore, that the increased release of endogenous norepinephrine from PC 12 cells by the phorbol ester competed with exogenous [3H]NE for uptake by the plasma membrane NE (uptake1) carrier into the cells. Two observations were in agreement with such a model: (i) an increase in the external NE concentration decreased the effect of PMA on the [3H]NE uptake; and (ii) desensitization of the protein kinase C by long term treatment of the PC 12 cells with phorbol ester abolished the PMA effect on both [3H]NE efflux and [3H]NE uptake.

Journal Article↗
PubMed1995

Sodium-dependent norepinephrine-induced currents in norepinephrine-transporter-transfected HEK-293 cells blocked by cocaine and antidepressants.

Transport of norepinephrine (NE+) by cocaine- and antidepressant-sensitive transporters in presynaptic terminals is predicted to involve the cotransport of Na+ and Cl-, resulting in a net movement of charge per transport cycle. To explore the relationship between catecholamine transport and ion permeation through the NE transporter, we established a human norepinephrine transporter (hNET) cell line suitable for biochemical analysis and patch-clamp recording. Stable transfection of hNET cDNA into HEK-293 (human embryonic kidney) cells results in lines exhibiting (1) a high number of transporter copies per cell (10(6)), as detected by radioligand binding and hNET-specific antibodies, (2) high-affinity, Na(+)-dependent transport of NE, and (3) inhibitor sensitivities similar to those of native membranes. Whole-cell voltage-clamp of hNET-293 cells reveals NE-induced, Na(+)-dependent currents blocked by antidepressants and cocaine that are absent in parental cells. In addition to NE-dependent currents, transfected cells posses an NE-independent mode of charge movement mediated by hNET. hNET antagonists without effect in non-transfected cells abolish both NE-dependent and NE-independent modes of charge movement in transfected cells. The magnitude of NE-dependent currents in these cells exceeds the expectations of simple carrier models using previous estimates of transport rates. To explain our observations, we propose that hNETs function as ion-gated ligand channels with an indefinite stoichiometry relating ion flux to NE transport. In this view, external Na+ and NE bind to the transporter with finite affinities in a cooperative fashion. However, coupled transport may not predict the magnitude or the kinetics of the total current through the transporter. We propose instead that Na+ gates NE transport and also the parallel inward flux of an indeterminate number of ions through a channel-like pore.

Adrenergic alpha-Agonists↗
PubMed2004

Uptake and release of norepinephrine by serotonergic terminals in norepinephrine transporter knock-out mice: implications for the action of selective serotonin reuptake inhibitors.

Our aim was to investigate the functional properties of the noradrenergic system in genetically modified mice lacking the norepinephrine transporter (NET). We measured the uptake and release of [(3)H]norepinephrine ([(3)H]NE) from hippocampal and cortical slices of NET(-/-) knock-out (KO) and NET(+/+) wild-type (WT) mice and investigated the presynaptic alpha2-adenoceptor-mediated modulation of NE release in vitro and in vivo. The [(3)H]NE uptake was reduced to 12.6% (hippocampus) and 33.5% (frontal cortex) of WT control in KO mice. The neuronal component of this residual uptake was decreased by 79.4 and 100%, respectively, when a selective serotonin reuptake inhibitor (SSRI) citalopram was present during the loading. The more preserved neuronal release of [(3)H]NE (hippocampus, 28.1%; frontal cortex, 74.4%; compared with WT) almost completely disappeared in both regions (94.1 and 95.3% decrease compared with KO, respectively) in the presence of citalopram, suggesting that [(3)H]NE was taken up and released by serotonergic varicosities. This was further supported by the finding that the release of [(3)H]NE from hippocampal slices of KO mice was not modulated by the alpha2-adrenoceptor antagonist 7,8-(methylenedioxy)-14-alpha-hydroxyalloberbane HCl, whereas the endogenous release of NE measured by microdialysis was even more efficiently enhanced by this drug in NET-deficient mice. These experiments indicate that serotonergic varicosities can accumulate and release NE as a result of the heterologous uptake of transmitters. Because the diffusion of NE may be spatially limited by serotonin transporters, the SSRIs, despite their selectivity, might enhance not only serotonergic but also noradrenergic neurotransmission, which might contribute to their antidepressant action.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed2002

Effect of differently induced plasma norepinephrine increments on norepinephrine sulfate formation.

We investigated whether similar increments in venous plasma norepinephrine (NE) concentration caused by exercise and by intravenous NE infusion will elevate plasma norepinephrine sulfate (NES) to similar concentrations. In randomized order venous plasma NE concentration was elevated to similar concentrations by bicycle exercise (BE; 65% VO(2)max) and by intravenous NE infusion at rest (INF; 0.14 microg/min/kg). N = 11 subjects participated in the study. Increments in plasma NE and the area under curve of plasma NE were similar during BE (11.2 +/- 1.3 nM; 411 +/- 23 nM/min; means +/- S.E.) and INF (12.6 +/- 1.9 nM; 429 +/- 27 nM/min). Plasma NES was significantly elevated to similar concentrations with BE (from 5.7 +/- 1.0 to 8.5 +/- 1.3 nM) and with INF (from 5.6 +/- 0.9 to 8.9 +/- 1.0 nM). Plasma NE and NES concentration during control conditions remained unchanged. Heart rate decreased significantly to 43 +/- 1 beats/min with INF and increased significantly to 162 +/- 3 beats/min with BE. Systolic blood pressure increased with both, INF and BE (155 +/- 3 mmHg; 179 +/- 6 mmHg, respectively). Present findings firstly show that intravenously infused NE is sulfoconjugated in humans, indicating that a major part of NE is sulfoconjugated in blood or at sites easily accessible from blood. Secondly, plasma NE may be a useful additional marker for NES release.

Adult↗
PubMed1983

Blood pressure and plasma norepinephrine concentrations after endogenous norepinephrine release by tyramine.

To determine whether small changes in sympathetic activity would cause detectable changes in plasma norepinephrine (NE) levels, and whether the effects of endogenously released and exogenous NE differ, we injected tyramine infusions and l-norepinephrine (l-NE), into six healthy subjects, and the changes in blood pressure (BP) and plasma NE were related. The mean increase in systolic BP was approximately 17 mm Hg with both infusions; diastolic BP increased with l-NE but did not rise significantly with tyramine. Heart rate fell more with l-NE than with tyramine infusions. The maximum increase in plasma NE levels was more than 500% during l-NE infusions but less than 200% with tyramine. There was no correlation between plasma NE and absolute levels of systolic BP when individual data were plotted for tyramine infusions, whereas mean group changes in systolic BP correlated strongly with mean group plasma NE, both during tyramine and l-NE infusions. The slope of the relationship was much steeper for tyramine than for l-NE. We conclude that the use of plasma NE to measure small differences in sympathetic activity among individuals is limited by interindividual variability, whereas changes in sympathetic activity within groups are more likely to be detected.

Adult↗