SEARCH · PubMed Health

Results for “Norepinephrine”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources

PubMed1996

Effect of endothelium on the aortic contraction induced by norepinephrine and KCl in isolated rat aorta.

Endothelium in aorta is known to contain releasable vasoactive agents. The purpose of the present study was to examine the effect of endothelium on the contraction induced by the membrane depolarizing agent KCl and by the alpha adrenoceptor agonist norepinephrine. It was found that the contraction induced by norepinephrine was bigger in denuded aorta at 1 x 10(-9) M and 1 x 10(-8) M norepinephrine, but the norepinephrine-induced contraction at 1 x 10(-7) M norepinephrine was not different between the denuded and control aortae. On the other hand, the contraction induced by KCl in denuded aorta was bigger at 10 mM KCl but smaller at 60 and 90 mM KCl in comparing with those determined in the presence of endothelium. These results indicate that the presence of endothelium alleviates the norepinephrine-induced contraction below 1 x 10(-7) M norepinephrine but potentiates the KCl-induced contraction at 60 mM KCl and above.

Adrenergic alpha-Agonists↗

PubMed1997

Comparison between alpha-1 adrenoceptor-mediated and beta adrenoceptor-mediated inotropic components elicited by norepinephrine in failing human ventricular muscle.

The purpose of our study was to investigate the inotropic response to the endogenous agonist norepinephrine mediated through alpha-1 adrenoceptors and to compare this response to that mediated through beta-adrenoceptors in failing human ventricular myocardium. We studied ex vivo the inotropic effect of norepinephrine in isometrically contracting trabecular myocardium from both ventricles of explanted hearts. By studying influence of appropriate adrenoceptor blockers, qualitative characteristics of the inotropic response and sensitivity of the inotropic response to cholinergic stimulation, it was revealed that norepinephrine evoked both alpha-1 and beta adrenoceptor-mediated inotropic effects in failing human ventricle myocardium. Quantitatively the inotropic responses to norepinephrine varied markedly between preparations, but the mean responses elicited through the respective adrenoceptor systems were of comparable magnitude. Concomitant stimulation of alpha-1 and beta adrenoceptors by norepinephrine alone revealed a contribution of an alpha-1 adrenoceptor-mediated component to the final and unopposed inotropic response. Differential sensitivity of the two adrenoceptor systems to norepinephrine depending on etiology of heart failure and possibly also thyroid status was observed. It is concluded that norepinephrine evokes an alpha-1 adrenoceptor-mediated inotropic effect comparable to that evoked through the beta adrenoceptors in failing human ventricular myocardium, and that this alpha-1 adrenoceptor-mediated inotropic effect may be of functional importance.

Adrenergic Antagonists↗

PubMed1993

Sodium- and chloride-dependent, cocaine-sensitive, high-affinity binding of nisoxetine to the human placental norepinephrine transporter.

Maternal-facing brush border membranes prepared from normal term human placentas possess the norepinephrine transporter. We investigated the interaction of nisoxetine with the human norepinephrine transporter by examining the binding of this ligand to the placental brush border membranes. Scatchard analysis revealed that nisoxetine bound with high affinity to a single class of binding sites in the membranes (dissociation constant = 13.8 +/- 0.4 nM). This value obtained from equilibrium experiments matched the value (11.2 nM) which was calculated using the association and dissociation rate constants. The maximal binding capacity (Bmax) was 5.1 +/- 0.1 pmol/mg of protein. The binding exhibited an absolute requirement for Na+ as well as Cl-. Presence of these ions enhanced the binding affinity without affecting Bmax. Kinetic analyses revealed that the coupling ratio of Na+/nisoxetine was 2, whereas the coupling ratio of Cl-/nisoxetine was 1. The binding was most potently inhibited by the ligands of the norepinephrine transporter (desipramine and nomifensine). The ligands of the serotonin transporter (imipramine, paroxetine, and fluoxetine) showed intermediate inhibitory potencies, whereas the ligands of the dopamine transporter (bupropion and GBR 12909) were the least potent. Among the monoamines, dopamine was the most potent inhibitor, followed by norepinephrine and serotonin. Though both cocaine and its analog RTI-55 were powerful inhibitors of the binding, RTI-55 was approximately 150 times more effective than cocaine. The inhibition of binding by norepinephrine, cocaine, and RTI-55 was competitive. Uptake of norepinephrine measured in membrane vesicles was found to be inhibited by treatment of the vesicles with phenylarsine oxide, a reagent specific for vicinal dithiol groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗

PubMed2005

Monoamine transporter inhibitors and norepinephrine reduce dopamine-dependent iron toxicity in cells derived from the substantia nigra.

The role of dopamine in iron uptake into catecholaminergic neurons, and dopamine oxidation to aminochrome and its one-electron reduction in iron-mediated neurotoxicity, was studied in RCSN-3 cells, which express both tyrosine hydroxylase and monoamine transporters. The mean +/- SD uptake of 100 microm 59FeCl3 in RCSN-3 cells was 25 +/- 4 pmol per min per mg, which increased to 28 +/- 8 pmol per min per mg when complexed with dopamine (Fe(III)-dopamine). This uptake was inhibited by 2 microm nomifensine (43%p < 0.05), 100 microm imipramine (62%p < 0.01), 30 microm reboxetine (71%p < 0.01) and 2 mm dopamine (84%p < 0.01). The uptake of 59Fe-dopamine complex was Na+, Cl- and temperature dependent. No toxic effects in RCSN-3 cells were observed when the cells were incubated with 100 microm FeCl3 alone or complexed with dopamine. However, 100 microm Fe(III)-dopamine in the presence of 100 microm dicoumarol, an inhibitor of DT-diaphorase, induced toxicity (44% cell death; p < 0.001), which was inhibited by 2 microm nomifensine, 30 microm reboxetine and 2 mm norepinephrine. The neuroprotective action of norepinephrine can be explained by (1) its ability to form complexes with Fe3+, (2) the uptake of Fe-norepinephrine complex via the norepinephrine transporter and (3) lack of toxicity of the Fe-norepinephrine complex even when DT-diaphorase is inhibited. These results support the proposed neuroprotective role of DT-diaphorase and norepinephrine.

Adrenergic Uptake Inhibitors↗

PubMed1984

Cerebellar norepinephrine in patients with Parkinson's disease and control subjects.

Norepinephrine was measured in postmortem cerebellar cortex of 22 non-neurological control subjects and nine patients with Parkinson's disease, using the high-performance liquid chromatography method with amperometric detection. In all control subjects, substantial amounts of norepinephrine was found in cerebellar cortex. There was a moderate negative correlation between age of control subjects and cerebellar norepinephrine concentration. In the patients with Parkinson's disease, the cerebellar cortical norepinephrine levels were significantly below normal. This is in accord with previously reported reduced norepinephrine levels in locus ceruleus and other regions of the parkinsonian brain. Although the main symptoms of Parkinson's disease are primarily caused by disturbed basal ganglia (dopamine) function, cerebellar dysfunction related to norepinephrine may contribute to some abnormalities of motor performance in this disorder.

Aged↗

PubMed1991

Norepinephrine-induced cardiac hypertrophy of the cat heart.

Norepinephrine administration causes progressive hypertrophy of the mammalian heart as measured by myocardial mass. The purpose of this study was to determine the growth response of the myocardial tissue components as well as the myocardial cell itself to norepinephrine. Young, adult cats were given low doses of norepinephrine in dextrose or dextrose alone twice daily for 15 days. On day 16, there were no changes in the animals body weight, right ventricular systolic pressure, right ventricular end-diastolic pressure, heart rate, cardiac index, or blood pressure. However, the right ventricle/body weight, the left ventricle/body weight and the total heart weight/body weight were increased significantly in the norepinephrine treated animals. The increase was on the order of 40%. The cardiac muscle cell was also significantly increased in size and both the right and left ventricular cardiac muscle cells exhibited a dramatic increase in size as measured by cross sectional area. Upon stereological examination it was found that the amount of hypertrophy as seen in the cardiac muscle cells was paralleled by the hypertrophy seen in the other tissue components of the myocardium. The volume density of the muscle cells, the interstitial components, as well as the blood vessel compartment were identical in the control and in the norepinephrine-treated groups. In conclusion, this study demonstrates that the response of the myocardium to norepinephrine is similar to that seen in response to a volume overload rather than that seen in response to pressure overload.

Animals↗

PubMed1980

An improved method for determination of plasma norepinephrine: isolation by boric acid gel and assay by selected ion monitoring.

An accurate and time-saving method for the determination of norepinephrine in human plasma is described. The whole device focused on an improvement in the pretreatment. One ml of human plasma was applied to a boric acid gel column without deproteinization and pH adjustment, and norepinephrine was eluted with 2 ml of a 1.3 M acetic acid in methanol solution. The pentafluoropropionic derivative of norepinephrine was analysed by gas chromatography mass spectrometry using deuterated norepinephrine as an internal standard. The level of plasma norepinephrine in healthy subjects at recumbency was 297 +/- 95 pg ml-1 (mean +/- SD). The lower limit of sensitivity was 25 pg ml-1 of norepinephrine in plasma.

Adult↗

PubMed1990

Norepinephrine-induced cholestasis in the isolated perfused rat liver is secondary to its hemodynamic effects.

In this study we examined the effect of pharmacological doses of various alpha-adrenergic agents on hepatic portal perfusion, organic anion uptake and bile secretion using the isolated perfused rat liver. Addition of norepinephrine at portal perfusate concentrations ranging from 0.01 to 100 mumol/L induced a dose-related increase in portal pressure with a twofold increment at the highest concentration. This was accompanied by an inhibition of hepatocellular uptake of taurocholate by 16.8% +/- 1.8% and of sulfobromophthalein (BSP) by 32.9% +/- 3.0% compared with controls. Moreover, a 22.5% +/- 3% decrease in bile flow rate and a 22.8% +/- 4% inhibition of biliary excretion of taurocholate were observed. Addition of other alpha-adrenergic agonist (epinephrine, dopamine and phenylephrine) at similar concentrations produced the same hepatic effects as observed with norepinephrine. During infusion of these alpha-adrenergic agents, trypan blue infusion revealed a patchy perfusion pattern of the liver surface compared with the homogeneously stained organs in controls. The hemodynamic alterations could be confirmed by electron microscopy examination that demonstrated that increased portal pressure produced by norepinephrine was associated with sinusoidal shunting. All hemodynamic, metabolic and biliary changes induced by norepinephrine could be entirely prevented by concomitant infusion of the alpha-antagonist phentolamine, thus indicating that norepinephrine-induced hepatic effects were mediated by alpha-receptors. In contrast, simultaneous addition of papaverine, an unspecific vasodilator, prevented the hemodynamic and the biliary changes of norepinephrine, but failed to modify the metabolic effects of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1997

Effect of aging on norepinephrine and phenylephrine stimulated lactate production by white adipocytes.

We have recently demonstrated that adipose tissue can produce lactate independently of lipolysis in insulin-resistant rats and that lactate production depends on alpha 1-adrenergic stimulation. In this study, we have investigated the influence of aging on norepinephrine-and-phenylephrine-stimulated lactate production and glycerol production. We showed that basal and norepinephrine stimulated lactate production were significantly increased in adipocytes isolated from old vs. young rats (0.165 +/- 0.006 vs. 0.055 +/- 0.008 for basal and 0.567 +/- 0.026 vs. 0.277 +/- 0.019 mumol lactate/10(6) cells/15 minutes for norepinephrine-stimulated lactate production, respectively, p < 0.05). The sensitivity of lactate production to norepinephrine stimulation in adipocytes isolated from old rats was significantly decreased (EC50 = 523 +/- 63.7 vs. 46.7 +/- 6.34 nM, respectively, p < 0.05). Maximal lactate production obtained with norepinephrine and phenylephrine was not significantly different in either group (0.567 +/- 0.026 vs. 0.520 +/- 0.036 in old and 0.277 +/9 0.019 vs. 0 275 +/- 0.017 mumol/10(6) cell/15 minutes in young rats, respectively, ns). Lactate production by adipocytes isolated from old rats were significantly less sensitive to phenylephrine stimulation compared with young (EC50 = 3.67 +/- 1.16 vs. 0.07 +/- 0.01 nM, respectively, p < 0.05) indicating that the effects of aging on norepinephrine and phenylephrine stimulation were probably induced by a decreased number of alpha 1-adrenoceptors. The mechanism by which aging increases adipocyte responsiveness of lactate production has not yet been elucidated.

Adipocytes↗

PubMed2002

Chronic treatment with imipramine or mirtazapine antagonizes stress- and FG7142-induced increase in cortical norepinephrine output in freely moving rats.

The effect of repeated administration of imipramine or mirtazapine, two antidepressant drugs with different mechanisms of action, was studied on the stress-induced increase in the extracellular concentration of norepinephrine in the prefrontal cortex of freely moving rats. Exposure to footshock in control rats induced a marked increase in extracellular norepinephrine concentrations in the prefrontal cortex (+120%). Long-term administration with imipramine or mirtazapine (10 mg/kg, i.p., twice or once a day, respectively, for 14 days) reduced (+50%) the effect of stress on basal norepinephrine output. Acute administration of FG7142 (30 mg/kg, i.p.), an anxiogenic benzodiazepine receptor inverse agonist, induced a marked increase in norepinephrine output (+90%) in control rats. In rats chronically treated with imipramine or mirtazapine this effect was completely antagonized. On the contrary, acute administration of these antidepressant drugs failed to reduce stress- and FG7142-induced increase in norepinephrine output. The plastic changes in the sensitivity of norepinephrine neurons to footshock stress and drug-induced anxiogenic stimuli may reveal a new important neuronal mechanism involved in the long-term modulation of emotional state. This action might be relevant for the anxiolytic and antidepressant effect of antidepressant drugs.

Animals↗

PubMed1999

The influence of kynurenine, neopterin, and norepinephrine on tubular epithelial cells and alveolar fibroblasts.

We have examined the effect of kynurenine, neopterin and norepinephrine on epithelial cells and fibroblasts: the total DNA synthesis (by adding 3H-thymidine), the mitotic index, the amount of pathological mitosis and apoptosis. We have observed that kynurenine, neopterin and norepinephrine induce pathological mitosis and apoptosis of epithelial cells of kidney. The total DNA synthesis increases by the incubation of the epithelial cells with neopterin and norepinephrine. We have found an increase of pathological mitosis after addition of kynurenine, neopterin and norepinephrine to fibroblast cell culture. The total DNA synthesis is promoted by neopterin and norepinephrine, while kynurenine does not alter it. These data allow us to suggest that kynurenine, neopterin and norepinephrine promote epithelial cell damage leading to cell death through apoptosis, and can therefore be added to the factors, which promote the pathological mitosis of fibroblasts.

Animals↗

PubMed1983

The effect of experimentally induced myocardial ischemia on the norepinephrine metabolism of the dog heart.

Myocardial ischemia is known to provoke an excess in circulating norepinephrine and thus be related to an increased irritability of the heart. In the present experiments, we studied the norepinephrine and potassium content, oxygen tension, and pH values of the effluent of coronary sinus after thoracotomy and catheter placement into the coronary sinus. Once a steady state was reached, the measurements were repeated in the fifth, tenth, 20th, and 60th minutes of experimental myocardial ischemia provoked by coronary ligation of the left anterior descending coronary artery. The parameters obtained were compared to the corresponding values measured in the peripheral vessels. The results indicate an increased release and probably an increased turnover of norepinephrine in the ischemic myocardium. The role of metabolism acidosis in the changes in norepinephrine metabolism was suggested. It is assumed that intracellular acidosis is involved in the enhanced accumulation and release of norepinephrine in the damaged myocardium and that an increase of norepinephrine concentration in the myocardium may be considered a risk factor in supporting heart function.

Animals↗

PubMed2002

Norepinephrine is superior to dopamine in increasing cortical perfusion following controlled cortical impact injury in rats.

Following traumatic brain injury catecholamines are routinely applied to increase cerebral perfusion. To date, it remains controversial if infusion of catecholamines is associated with diminished cerebral perfusion due to catecholamine-mediated vasoconstriction. The aims of the present study were to investigate the effects of norepinephrine and dopamine on cortical perfusion and brain edema following controlled cortical impact injury (CCII) in rats. Four hours after CCII, rats (n = 22) received either norepinephrine or dopamine with the aim of increasing MABP to 120 mm Hg for 90 minutes. Control rats were given NaCl. Cortical perfusion was measured before, during, and after catecholamine infusion using Laser Doppler flowmetry. Brain swelling was determined directly after the study period (8 hrs after CCII). Following CCII cortical perfusion was reduced by 40% compared to pre-trauma values in all rats. Parallel to the increases in MABP, cortical perfusion was significantly elevated under norepinephrine and dopamine, respectively (p < 0.05). Despite similar MABP values this increase was mostly sustained under norepinephrine. In control rats cortical perfusion remained diminished. Brain swelling was similar in all groups. Both norepinephrine and dopamine significantly increased cortical perfusion following CCII. Norepinephrine, however, was superior to dopamine in CBF. Based on increased CBF and unchanged brain swelling catecholamine-mediated vasoconstriction does not seem to occur under the present study design.

Animals↗

PubMed1980

Effect of increased pancreatic islet norepinephrine, dopamine and serotonin concentration on insulin secretion in the golden hamster.

The purpose of this study was to determine if increased concentrations of pancreatic islet norepinephrine, dopamine, or serotonin after insulin secretion. Golden hamsters received intraperitoneal injections of the norepinephrine precursor DL-threo-dihydroxyphenylserine, the dopamine precursor L-3,4-dihydroxyphenylalanine, or the serotonin precursor 5-hydroxytryptophan with and without pretreatment of the hamsters with the monoamine oxidase inhibitor tranylcypromine. Administration of the monoamine precursors to animals pretreated with tranylcypromine resulted in a mean increase in plasma glucose of 192% and a mean decrease in plasma insulin of 58%. Using a collagenase isolation technique, islets from control and treated animals were evaluated for monoamine content and insulin secretory capacity. The monoamine concentrations in control islets, in mumol/kg wet weight, were: norepinephrine 42 +/- 8; dopamine 8 +/- 2; and serotonin 26 +/- 9. Administration of the appropriate precursor to control hamsters resulted in a 1.9-fold (norepinephrine), 6-fold (dopamine), and 22-fold (serotonin) increase in monoamines. There was no alteration in the glucose (16.3 mmol/l)-stimulated in vitro insulin secretion from islets obtained from these hamsters. Administration of the precursors to hamsters pretreated with tranylcypromine resulted in a 3.5-fold (norepinephrine), 22-fold (dopamine), and 59-fold (serotonin) increase in monoamines. Glucose-stimulated in vitro insulin secretion from islets obtained from these hamstes was completely blocked. This study suggest that high concentrations of norepinephrine, dopamine, and serotonin in the pancreatic islets can decrease glucose-stimulated insulin secretion.

5-Hydroxytryptophan↗

PubMed1983

The effects of intravenous norepinephrine on the local coupling between glucose utilization and blood flow in the rat brain.

Norepinephrine was infused intravenously in two groups of normal, awake rats. In one group local cerebral glucose utilization (LCGU) was measured by the deoxyglucose method (Sokoloff et al. 1977b); in the other group local cerebral blood flow (LCBF) was determined by the iodoantipyrine method (Sakurada et al. 1978). The experiments were performed during a stable state in which the heart rate was reduced between 36% (LCGU experiments) and 27% (LCBF experiments). Norepinephrine infusion reduced LCGU in all 39 structures measured between - 18 and - 37% from control values obtained in a group of normal non-infused rats. The decrease in LCGU was significant (P less than 0.05) in 38 of the 39 structures tested. LCBF was increased but not statistically significantly in most of the structures examined. When the LCGU values of the various structures during norepinephrine infusion were correlated with their corresponding LCBF values, a tight correlation (r = 0.94) was found indicating a close coupling between LCGU and LCBF during norepinephrine infusion. When compared to the relationship between LCGU and LCBF in a normal, non-infused control group, the slope of the regression line was increased significantly (P less than 0.01) by the norepinephrine infusion, indicating a resetting of the coupling mechanism. This means that, at a given metabolic rate, a higher blood flow is needed to perfuse a brain structure during norepinephrine infusion than during control conditions.

Animals↗

PubMed1986

Depression of neuron responses to acetylcholine by combined application of norepinephrine and substrates of the tricarboxylic acid cycle.

The possible relationship between the function of nicotinic acetylcholine receptors in Lymnaea stagnalis neurons and energy metabolism was studied. Oxidative phosphorylation was activated by treatment of neurons with substrates of the tricarboxylic acid cycle and norepinephrine. Transmembrane currents induced by acetylcholine in isolated neurons were measured by voltage clamp. Succinate dehydrogenase activity was determined histochemically in the same neurons. Cyclic adenosine monophosphate concentration in ganglia were assayed by the protein saturation method of Gilman (1970). When used alone, succinate depressed the responses of about 50% of neurons to acetylcholine. Norepinephrine did not affect the acetylcholine-induced currents but almost doubled the inhibitory action of succinate. The mixture of norepinephrine and isocitrate also diminished the responses to acetylcholine but to a lesser extent than norepinephrine with succinate. A short-term exposure of the ganglia to succinate with norepinephrine led to the activation of succinate dehydrogenase in neurons and a threefold increase in cyclic adenosine monophosphate concentrations in ganglia. When used alone, norepinephrine doubled the cyclic adenosine monophosphate concentration. The results obtained suggest energy-dependent regulation of acetylcholine receptors.

Acetylcholine↗

PubMed1986

Effect of glucose and fat feeding on norepinephrine turnover in rats.

The norepinephrine turnover in organs of glucose-fed and fat-fed rats were compared to those of starved rats. Rats fed only glucose had higher rates of norepinephrine turnover than starved rats in heart, pancreas, kidney, liver, and lung. The effect of glucose-feeding on norepinephrine turnover was most pronounced in heart (+197%) and pancreas (+120%), which were examined in the fat feeding study. Rats fed only fat showed the same suppression of insulin levels as fasting rats, and a greater reduction in plasma glucose levels. However, their norepinephrine turnover in heart (+182%) and pancreas (+173%) was similar to that of glucose-fed rats. Thus glucose and fat increase norepinephrine turnover in the absence of any other nutrients. If these nutrients increase norepinephrine turnover via the same intermediate signal, it cannot be insulin or increased glucose metabolism.

Animals↗

PubMed1994

Effects of norepinephrine on right ventricular function in septic shock patients.

OBJECTIVE: To study the effects of norepinephrine on right ventricular function in patients with hyperdynamic septic shock. DESIGN: Prospective, open study. SETTING: A 15 bed ICU in a university hospital. PATIENTS: 9 patients with hyperdynamic septic shock (SBP < 90 mmHg, Cl > or = 4 l.min-1.m-2, SVRI < or = 850 dynes.s.cm-5m-2 and oliguria). INTERVENTIONS: Plasma volume expansion was used to correct a suspected volume deficit and then, norepinephrine infusion was started and titrated to restore systemic blood pressure to the normal range (mean infusion rate: 1.1 +/- 0.2 mcg.kg-1.min-1). Norepinephrine was the only vasoactive agent used in these patients. MEASUREMENTS AND RESULTS: A modified Swan-Ganz catheter mounted with a fast response thermistor was inserted in each patient, allowing repeated measurements of RVEDVI and RVEF. At time of inclusion to the study, all but one patient had elevated MPAP (23 +/- 4 mmHg) and RVEF < or = 50%, and all patients had RVEDVI > or = 90 ml.m-2. During norepinephrine infusion, MAP increased from 51 +/- 9 to 89 +/- 10 mmHg (p < 0.0001), PVRI increased from 204 +/- 35 to 286 +/- 63 dynes.s.cm-5.m-2 (p < 0.05), and despite this increase in right ventricular afterload, no detrimental effect in RVEF (36 +/- 11 to 36 +/- 10%) or in RVEDVI (116 +/- 30 to 127 +/- 40 ml.m-2) was observed. A Frank-Starling relationship for the right ventricle was constructed by plotting an index of ventricular performance (RVSWI) against an index of ventricular preload (RVEDVI). A significant upward shift to the right of the relationship was observed during norepinephrine infusion. CONCLUSION: It was concluded that norepinephrine exerted a favourable effect on right ventricular function.

Adult↗