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Results for “Norepinephrine”

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PubMed1992

Characterization of ATP receptor which mediates norepinephrine release in PC12 cells.

PC12 cells, a rat pheochromocytoma cell line, has been reported to release norepinephrine in response to extracellular ATP in the presence of extracellular Ca2+. The potency order of ATP analogues was adenosine 5'-O-(3-thiotriphosphate) greater than ATP greater than adenosine 5'-O-(1-thiotriphosphate) = 2-methylthioadenosine 5'-triphosphate (MeSATP) greater than 2'- and 3'-O-(4-benzoyl-benzoyl)ATP (BzATP) greater than ADP greater than 5-adenylylimidodiphosphate. Adenosine 5'-O-(2-thiodiphosphate), beta, gamma-methyleneadenosine 5'-triphosphate, AMP and adenosine were inactive. The ATP action in the absence of extracellular Ca2+, suggests a small but appreciable contribution of intracellular Ca2+ mobilization, for norepinephrine release. However, for some ATP derivatives, like BzATP, almost no contribution of the phospholipase C-Ca2+ pathway is suggested, based on their low activity in inositol phosphates production. To identify the ATP-receptor protein, PC12 cell membranes were photoaffinity-labeled with [32P]BzATP. SDS-PAGE analysis showed that a 53-kDa protein labeling was inhibited by ATP and its derivatives, as well as by P2-antagonists, suramin and reactive blue 2, which inhibit the nucleotide-induced norepinephrine release. The inhibitory activity of the nucleotides was, in parallel with their potency, to induce norepinephrine release. Despite their inability to release norepinephrine, GTP and GTP gamma S inhibited the BzATP labeling, suggesting the participation of a putative G protein in the ATP-receptor-mediated actions. We suggest that the 53-kDa protein on the PC12 cell surface is an ATP receptor, which mediates the norepinephrine release, depending, mainly, on extracellular Ca2+ gating.

Adenosine Triphosphate↗

PubMed1992

Effect of diltiazem on norepinephrine-induced acute left ventricular dysfunction.

The present study has examined the role of diltiazem as a protective agent in a canine model of norepinephrine cardiotoxicity. Effects of diltiazem, 20 micrograms/kg/min x 5 min pretreatment followed by 10 micrograms/kg/min x 90 min, or saline infusion were examined at baseline and 1 h after infusion of norepinephrine, 4 micrograms/kg/min for 90 min, in closed-chest anesthetized dogs. Left ventricular function was assessed by equilibrium radionuclide angiogram and two-dimensional echocardiogram. In 7 saline experiments, hypotension and increased heart rate were observed at 1 h post infusion. In the diltiazem-treated group (n = 7), mean arterial pressure and heart rate were unchanged. In the saline group, left ventricular ejection fraction fell from 0.50 +/- 0.04 to 0.28 +/- 0.04. Left ventricular ejection fraction was unchanged in the diltiazem-treated group: 0.52 +/- 0.03 to 0.55 +/- 0.07. Left ventricular end-diastolic volume was increased at 1 h post infusion in saline controls but not in the diltiazem-treated group. Measurement of fractional shortening from two-dimensional echocardiograms also indicated left ventricular dysfunction in the saline but not diltiazem-treated groups. Left ventricular end-systolic wall stress following norepinephrine infusion was significantly increased in the saline but not diltiazem-treated groups: 122.7 +/- 18.7 vs 67.6 +/- 19.7 g/cm2, respectively. In dogs receiving saline without norepinephrine infusion, no significant changes occurred over the course of the experiment. Histologic examination showed mild contraction band necrosis in saline controls but not in sham saline dogs. Diltiazem showed intermediate histologic evidence of injury, which was not further quantified. This study suggests that effects of norepinephrine on left ventricular function in the canine model of norepinephrine cardiotoxicity may be largely due to increased wall stress following a prolonged increase in afterload. Diltiazem pretreatment afforded significant protection of left ventricular function.

Animals↗

PubMedDate not supplied

Influence of age on norepinephrine content in arteries and veins of Fischer 344 rats.

The norepinephrine content of blood vessels in male Fischer 344 rats aged 6, 12, 20 and 27 months was measured by electrochemical detection after alumina extraction and high-performance liquid chromatography separation. With the exception of the superior mesenteric artery which showed no age-related changes in norepinephrine content and the caudal artery which showed an increase from 12 to 27 months of age, all other arteries examined (renal, femoral, saphenous, superficial epigastric, and popliteal) showed a significant decline in norepinephrine content with advancing age. In contrast, the content of norepinephrine in the renal, femoral, saphenous and superior mesenteric veins remained constant at all ages. Since norepinephrine in the blood vessel wall is predominantly localized to sympathetic nerve endings, the decline in norepinephrine content in most arteries of old rats may reflect a selective decrease in the density of sympathetic neurons or alternatively an age-related alteration in the metabolic properties of these sympathetic nerve endings.

Aging↗

PubMed1996

Increased concentrations of plasma epinephrine and norepinephrine in patients with eclampsia.

We measured plasma catecholamine concentrations on admission (after eclamptic fit) and after 6 days of delivery in 21 eclamptic patients and on admission in 15 normotensive pregnant women in Bangladesh. Plasma epinephrine and norepinephrine concentrations in eclamptic patients were significantly higher on admission than those of normotensive pregnant women (P < 0.0001). Plasma catecholamine concentrations and mean arterial blood pressure had return to be almost normal as normotensive pregnant women after 6 days of delivery, resulting in no correlation between mean arterial blood pressure and plasma catecholamines. On admission (after eclamptic fit) mean arterial blood pressure was positively correlated with plasma epinephrine (r = 0.626, P < 0.002) and norepinephrine (r = 0.553, P < 0.008) concentrations in patients with eclampsia. The amount of proteinuria was also significantly correlated with plasma epinephrine (r = 0.515, P < 0.02) and norepinephrine (r = 0.606, P < 0.003) concentrations. Number of convulsions was significantly correlated with concentrations of plasma epinephrine (r = 0.514, P < 0.02), norepinephrine (r = 0.521, P < 0.01) and mean arterial blood pressure (r = 0.535, P < 0.01). A positive correlation was found between time passed after convulsion with plasma epinephrine (r = 0.515, P < 0.02) and norepinephrine (r = 0.570, P < 0.006) concentrations. These suggested that the increased plasma levels of epinephrine and norepinephrine in eclamptic patients were well correlated with the severity of the clinical features of eclampsia.

Adult↗

PubMed1994

The protective effect of superoxide dismutase and catalase against formation of reactive oxygen species during reduction of cyclized norepinephrine ortho-quinone by DT-diaphorase.

Norepinephrine was oxidized by the Mn(3+)-pyrophosphate complex to the corresponding o-quinone at pH 6.5. Cyclized norepinephrine ortho-quinone showed an absorption maximum at 289 and 483 nm. No oxygen consumption was observed during oxidation of norepinephrine to o-quinone by Mn3+ and subsequent cyclization. The reduction of cyclized norepinephrine ortho-quinone to the corresponding hydroquinone was catalyzed by DT-diaphorase. However, the hydroquinone formed proved to be unstable in the presence of oxygen, since reduction of cyclized norepinephrine o-quinone by DT-diaphorase was accompanied by continuous oxidation of NADH and oxygen consumption. Addition of the chelator DETAPAC or SOD to the incubation mixture during reduction of cyclized norepinephrine ortho-quinone by DT-diaphorase strongly inhibited NADPH oxidation and oxygen consumption, suggesting that manganese and superoxide radicals were involved in hydroquinone autoxidation. Elimination of the effects of superoxide radicals, manganese and H2O2 on autoxidation of hydroquinone by addition of SOD, catalase and DETAPAC to the incubation mixture resulted in a 79% inhibition of NADH oxidation, suggesting that 21% of the autoxidation is oxygen-dependent. However, the effect of these additions on oxygen consumption was even more pronounced (93% inhibition).

Animals↗

PubMed1991

Calcium antagonists inhibit contractions to norepinephrine in the rat aorta, in the absence, but not in the presence of the endothelium.

1. To compare the effect of diltiazem and verapamil on the responsiveness of vascular smooth muscle to norepinephrine in the presence and absence of the endothelium, rings of rat aorta were studied in organ chambers. 2. The removal of the endothelium decreased the ED50 to norepinephrine and augmented the maximal response to the catecholamine. 3. The contraction to norepinephrine consisted of a rapid initial (phasic) and a (tonic) part. The tonic part was reduced in the presence of the endothelium. 4. Diltiazem shifted the concentration-response curve to norepinephrine to the right only in rings without endothelium and reduced the difference in maximal response between rings with and without endothelium. 5. Verapamil abolished the difference in sensitivity (ED50) between rings with and without endothelium. 6. Oxyhemoglobin prevented the inhibitory effect of the endothelium on the response to norepinephrine, and unmasked a shift of the ED50 to the catecholamine to the right by diltiazem in rings with endothelium. 7. These experiments suggest that spontaneously released endothelium-derived relaxing factor(s) is a functional antagonist of norepinephrine-induced contractions, presumably by reducing the stimulated influx of extracellular Ca2+.

Animals↗

PubMed1986

Simultaneous secretion of catecholamines from the adrenal medulla and of [3H]norepinephrine from sympathetic nerves from a single test preparation: different effects of agents on the secretion.

The uptake and release of catecholamines was investigated in the isolated perfused adrenal gland of the rat after preloading the preparation with [3H]norepinephrine, and the effects of various agents were examined on the stimulation-evoked secretion of catecholamines and total tritium. Large quantities of tritium were found in the adrenal medulla after either intravenous injection of [3H]norepinephrine to the rat, or perfusion of the isolated adrenal gland with Krebs-bicarbonate solution containing [3H]norepinephrine. The retention of the tritium was inhibited 90% by desipramine. Acute treatment with guanethidine and chronic treatment with 6-hydroxydopamine abolished the secretion of tritium without affecting the secretion of catecholamines evoked at 1 Hz. Nicotine, muscarine and acetylcholine enhanced the secretion of catecholamines but not tritium, whereas tyramine and ephedrine enhanced the secretion of tritium but not catecholamines. It is concluded that chromaffin cells do not possess the norepinephrine uptake mechanism and that the uptake of [3H]norepinephrine occurs mainly in sympathetic nerve terminals present in the adrenal gland and the surrounding blood vessels (adrenal and renal veins). The differential localization of [3H]norepinephrine and catecholamines allowed us to test the effects of a variety of pharmacological agents that alter neurotransmitter release by acting on receptors on the neuronal membrane, acting on sodium and potassium channels, or acting to alter the intracellular concentrations of adenosine 3',5'-cyclic monophosphate and protein kinase C. Transmural stimulation (1 Hz for a total of 300 pulses) markedly enhanced the release of catecholamines and tritium which was blocked by tetrodotoxin (sodium channel-blocker) and potentiated by tetraethylammonium and gallamine (potassium channel-blockers). Phentolamine, an alpha adrenergic blocking agent which acts on both alpha-1 and alpha-2 receptors, caused a 3- to 4-fold facilitation of the tritium secretion while inhibiting catecholamine secretion by 45%. [Met]enkephalin almost completely inhibited the evoked-secretion of tritium but had very little effect on the secretion of catecholamines. Forskolin inhibited the tritium secretion by 80% but produced more than a 2-fold facilitation of catecholamine secretion. Phorbol 12,13-dibutyrate caused facilitation of evoked secretion of both catecholamines and tritium. A combination of phorbol ester and forskolin had a synergistic effect on stimulation-evoked secretion of catecholamines, whereas phorbol ester partially reversed the inhibitory effects of forskolin on the tritium secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Medulla↗

PubMed1990

Propranolol-sensitive and phenoxybenzamine-insensitive binding of norepinephrine to endogenous lipid droplets from rat adipocytes.

Norepinephrine, epinephrine, and isoproterenol at concentrations of 5.5 x 10(-8) M were found to elicit lipolysis in a cell-free system containing lipid droplets from fat cells and lipase solution. In the cell-free system, the beta-blockers propranolol and dichloroisoproterenol at concentrations of 1 microM inhibited lipolysis induced by norepinephrine, whereas similar concentrations of the alpha-blockers phenoxybenzamine and yohimbine did not inhibit lipolysis. The binding of norepinephrine to endogenous lipid droplets was inhibited by propranolol, but not by phenoxybenzamine. We concluded that the propranolol-sensitive, phenoxybenzamine-insensitive binding of norepinephrine to endogenous lipid droplets is involved in lipolysis in fat cells. Treatment of endogenous lipid droplets with phospholipase C, but not phospholipase D, trypsin, chymotrypsin, or neuraminidase, inhibited the propranolol-sensitive binding of norepinephrine to the droplets. These results suggest that the phosphate group of phospholipid in endogenous lipid droplets may be the site of propranolol-sensitive binding of norepinephrine. The physiological significance of the propranolol-sensitive binding is discussed.

Adipose Tissue↗

PubMed1992

Norepinephrine-induced Ca2+ current inhibition in adult rat sympathetic neurons does not require protein kinase C activation.

Experiments were performed to investigate if protein kinase C is involved in the norepinephrine-induced alpha 2-adrenoceptor-mediated inhibition of the Ca2+ current in adult rat superior cervical ganglion neurons. Ca2+ currents were recorded from dispersed superior cervical ganglion neurons, acutely isolated from adult rats, using the whole-cell patch-clamp technique. Both norepinephrine and the protein kinase C activator, 1,2-dioctanoylglycerol (diC8) decreased the Ca2+ current induced by step depolarizations to +10 mV from a holding potential of -80 mV. In the presence of norepinephrine, the Ca2+ current rising phase was adequately fit by a double exponential with a second time constant much larger than control, whereas in the presence of diC8 the rising phase became mono-exponential and the current displayed a prominent decay. Control tail current activation curves were described by the sum of two Boltzmann functions. Both norepinephrine and diC8 reduced peak tail current amplitude. Norepinephrine preferentially reduced the component activated at more hyperpolarized potentials, while diC8 preferentially reduced the component activated at more depolarized potentials. Intracellular application of three protein kinase C inhibitors: protein kinase C pseudosubstrate (PKC-19-36) (2 microM), staurosporine (1 microM) and 1-(5-isoquinolinylsulonyl)-2-sulfonylpiperazine (H-7) (50 microM), failed to affect norepinephrine-induced Ca2+ current inhibition. In addition, these protein kinase C inhibitors did not decrease the Ca2+ current inhibition induced by diC8.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

In vitro measurement of endogenous norepinephrine release from small blood vessels with short stimulation trains.

We have previously developed a low-volume perfusion-superfusion system for studying neurotransmitter release in small blood vessels. We now extend this technique to allow for the measurement of neurotransmitter release with short stimulation trains in order to examine modulating factors such as activation of prejunctional receptors or the effects of altered external calcium. Segments of rat tail artery were perfused in the presence of deoxycorticosterone and cocaine (10(-5) M). For short trains, nerves were activated with five sequential trains, each 4 sec in length (total of 160 pulses) at 8 Hz. For long trains, nerves were activated continuously for 3 min for a total of 1440 pulses. Norepinephrine in the perfusate and tissue norepinephrine were quantitated with high-performance liquid chromatography (HPLC) and electrochemical detection. Fractional norepinephrine release was significantly greater with short as compared to long trains when extracellular calcium was maintained at 1.6 mM. When nerves were stimulated with short trains, fractional norepinephrine release was very sensitive to altered extracellular calcium, with a significant decline when extracellular calcium was reduced to 1 mM and a significant increase when extracellular calcium was increased to 5 mM. In contrast, with long-stimulation trains increases or decreases in calcium had no effect on fractional norepinephrine release. This unique method facilitates the study of norepinephrine release with short trains or low-frequency activation and will also make it easier to study presynaptic receptor function as well as interactions between extracellular calcium and presynaptic effectiveness.

Animals↗

PubMed2004

Norepinephrine transporter function and desipramine: residual drug effects versus short-term regulation.

Previous research has shown that exposure of norepinephrine transporter (NET)-expressing cells to desipramine (DMI) downregulates the norepinephrine transporter, although changes in the several transporter parameters do not demonstrate the same time course. Exposures to desipramine for <1 day reduces only radioligand binding and uptake capacity while transporter-immunoreactivity is unaffected. Recent demonstration of persistent drug retention in cells following desipramine exposures raises the possibility that previous reported changes in the norepinephrine transporter may be partly accountable by residual drug. In this study, potential effects of residual desipramine on norepinephrine transporter binding and uptake were re-evaluated following exposures of PC12 cells to desipramine using different methods to remove residual drug. Using a method that minimizes residual drug, exposure of intact PC12 cells to desipramine for 4h had no effect on uptake capacity or [(3)H]nisoxetine binding to the norepinephrine transporter, while exposures for > or =16 h reduced uptake capacity. Desipramine-induced reductions in binding to the transporter required >24 h or greater periods of desipramine exposure. This study confirms that uptake capacity of the norepinephrine transporter is reduced earlier than changes in radioligand binding, but with a different time course than originally shown. Special pre-incubation procedures are required to abolish effects of residual transporter inhibitor when studying inhibitor-induced transporter regulation.

Adaptation, Physiological↗

PubMed2004

Desensitization of the inhibitory effect of norepinephrine on insulin secretion from pancreatic islets of exercise-trained rats.

The effect of exercise training (9 weeks of running) on norepinephrine-induced inhibition of insulin secretion was examined in rat islets. Insulin secretions from islets in the presence of glucose (> or =5.5 mmol/L) were significantly lower in trained (TR) than in control rats (CR). Norepinephrine inhibited 5.5 mmol/L glucose-stimulated insulin secretions and cyclic adenosine monophosphate (cAMP) contents in a dose-dependent manner in CR. Norepinephrine (10 micromol/L)-induced inhibition of insulin secretion was reversed by the blockade of the alpha(2)-adrenergic receptor in CR, but not in TR. Exercise training substantially shifted the dose-dependent curve for clonidine-induced inhibition of insulin secretions and that of cAMP contents to the right. Exercise training did not alter the density of the alpha(2)-adrenergic receptor either per islet or per protein of islet crude membrane. However, exercise training significantly reduced the protein expression of G alpha i-2 without change in G alpha i-2 mRNA. In CR but not in TR, norepinephrine significantly inhibited insulin secretions elicited by a combination of high glucose, a protein kinase C activator, and an adenylate cyclase activator under Ca(2+)-free conditions. Thus, exercise training appears to provoke a decreased expression of G alpha i-2 protein. This, at least in part, results in loss of the inhibitory effect of norepinephrine either on cAMP content or on insulin secretion at the post-calcium events in stimulus-secretion coupling, which, in turn, leads to the blunted inhibitory effects of norepinephrine on insulin secretion.

Adrenergic alpha-Agonists↗

PubMed2005

Nitric oxide from the laterodorsal tegmental neurons: its possible retrograde modulation on norepinephrine release from the axon terminal of the locus coeruleus neurons.

Nitric oxide released from the cholinergic neurons in the pons may play important roles in sleep-wake regulation. However, there are few reports demonstrating the mechanisms of nitric oxide release in the cholinergic neurons in the pons. The present study investigated the effects of drug delivery of N-methyl-D-aspartic acid on nitric oxide and the neurotransmitters released in the laterodorsal tegmental nucleus (LDT), one of the major cholinergic cell groups in the pons, in rats by in vivo microdialysis with a view to clarifying nitric oxide functions in the cholinergic system. The application of N-methyl-D-aspartic acid (1 mM) into the LDT induced a significant increase in NO(2)and NO(3) for 40 min (P<0.001). Furthermore the same dose of N-methyl-D-aspartic acid induced a significant increase in cyclic GMP for 30 min (P<0.05), as well as in acetylcholine (P<0.001) and norepinephrine for 15 min (P<0.001). 3-(4-Morpholinyl)-sydonone imine hydrochloride (a nitric oxide donor, 5 mM) also induced significant increase in norepinephrine (P<0.05). Pretreatment with 1 mM 2-amino-5-phosphonopentanoic acid (an antagonist of N-methyl-D-aspartic acid receptor) prevented the N-methyl-D-aspartic acid-induced increase in cyclic GMP (P<0.01), acetylcholine and norepinephrine (P<0.01), while that with 1 mM N(G)-nitro-L-arginine (an inhibitor of nitric oxide synthase) prevented the increase in cyclic GMP (P<0.01) and norepinephrine (P<0.01) but not in acetylcholine. These results suggested that nitric oxide release in the LDT induced by activation of the N-methyl-D-aspartic acid receptor on the cholinergic neurons of the LDT, then through the cyclic GMP system, facilitates norepinephrine release from the terminals of noradrenergic neurons in the locus coeruleus. Based on these findings, we propose a possible role of nitric oxide in the LDT is as a retrograde regulator of norepinephrine release from the locus coeruleus.

Acetylcholine↗

PubMed2005

Management of septic shock with a norepinephrine-based haemodynamic algorithm.

UNLABELLED: Management of septic shock (SS) with a norepinephrine (noradrenaline)-based haemodynamic algorithm. INTRODUCTION: The choice of the best vasopressor for haemodynamic management of septic shock is controversial. Nevertheless, very few studies have been focused on evaluating different management algorithms. The aim of this study was to evaluate the performance of a norepinephrine (NE)-based management protocol. Experience with NE as the initial vasopressor, even if not comparative, could bring relevant data for planning future trails. We also wanted to evaluate the compliance of critical care physicians and nurses with haemodynamic management protocol. PATIENTS AND METHOD: A norepinephrine-based algorithm for the management of septic shock that commands different sequential interventions according to its requirements, was applied prospectively to 100 consecutive septic shock patients. RESULTS: Norepinephrine was used as the first vasoactive drug in all patients with a maximum dose of 0.31+/-0.3 microg kg(-1)min(-1) and an ICU mortality of 33%. Physicians applied correctly all the steps of the algorithm in 92% of the patients. Applying the algorithm, avoided the use of pulmonary artery catheter in 31 patients and led to use of lower doses of vasoactive agents than in many other clinical experiences. CONCLUSION: In conclusion, our data support extended use of an algorithm based on norepinephrine for treating septic shock patients. This is the first clinical study that uses NE as the initial vasopressor drug systematically, and although not comparative, the mortality rates adjusted to APACHE II, are comparable to other studies. It also gives support for future clinical trials comparing norepinephrine with dopamine in this setting.

Aged↗

PubMed1988

Relative significance of dopamine receptors, beta adrenoceptors and norepinephrine uptake inhibition in the cardiovascular actions of dopexamine hydrochloride.

Studies in our laboratory have confirmed that dopexamine hydrochloride is a potent beta 2-adrenoceptor and DA1-dopamine receptor agonist. We examined the effects of dopexamine hydrochloride on both cardiac contractile force, determined by use of a Walton-Brodie strain-gauge arch sutured to the right ventricle, and heart rate in anesthetized dogs. Dopexamine hydrochloride increased cardiac contractile force and heart rate and decreased blood pressure. After administration of the ganglionic blocking agents, hexamethonium and atropine, or the selective beta 1-adrenoceptor antagonist, atenolol, the positive inotropic and chronotropic effects of dopexamine hydrochloride were reduced or eliminated, demonstrating that the drug had little or no direct beta 1-adrenoceptor action and that a myocardial beta 2-adrenoceptor action was not involved in its cardiac effects. During these investigations, dopexamine hydrochloride was found to be an inhibitor of norepinephrine uptake, potentiating the cardiac effects of both exogenously administered norepinephrine and norepinephrine released from sympathetic nerves. These results led to the following conclusions: Dopexamine hydrochloride stimulates the heart by 2 mechanisms--(1) baroreceptor-mediated release of norepinephrine resulting from hypotension produced by beta 2 adrenoceptor and DA1 dopamine receptor-mediated vasodilatation, and (2) potentiation of the released norepinephrine due to prevention of norepinephrine uptake by sympathetic nerves. The latter mechanism may be involved in the cardiac stimulation observed in patients with congestive heart failure and shock, since excessive sympathetic activity and elevated catecholamine levels are present in these conditions.

Animals↗

PubMed1999

Plasma norepinephrine and prediction of outcome in major depressive disorder.

BACKGROUND: Several epidemiologic and clinical factors have been shown to predict long term outcome in major depressive disorder (MDD). The value of biological predictors has not been extensively studied. This study examined whether plasma norepinephrine may be useful in predicting outcome in MDD. METHODS: Forty patients were followed up 8 years after an index major depressive episode. Three outcome variables were assessed: time to first recurrence (the primary outcome measure), the Lee and Murray criteria and the Depression Outcome Scale (DOS). The results were examined against plasma norepinephrine value, at the index episode, using survival analysis and linear regression. RESULTS: High plasma norepinephrine at the index episode was positively and significantly associated with time to first recurrence for patients with nonpsychotic MDD (n = 31, chi 2 = 8.38, on 1 df, p < .01). Similarly, plasma norepinephrine was significantly associated with good global outcome, both using Lee and Murray criteria (n = 34, adjusted R2 = .24, p < .01) and DOS criteria (n = 31, adjusted R2 = .17, p < .01) for this group of patients. In contrast, plasma norepinephrine was not significantly related to outcome for MDD with psychotic features. CONCLUSIONS: Plasma norepinephrine at index episode seems to be a predictor of outcome in MDD.

Adult↗

PubMed2000

Systemic angiotensin II and volume expansion release norepinephrine in the preoptic recess.

The periventricular tissue surrounding the anteroventral portion of the third cerebral ventricle (AV3V) of the preoptic recess is critical for several responses evoked by central and peripheral angiotensin II (ang II), and the natriuresis produced by extracellular fluid volume expansion. In addition, several other studies have suggested that the pressor and natriuretic responses evoked by these stimuli are regulated by activation of noradrenergic systems in AV3V tissue. The purpose of the present experiments was to directly determine if i.v. infusion of ang II and volume expansion increase norepinephrine release in the AV3V area using in vivo microdialysis. Male, Sprague-Dawley rats were implanted with microdialysis probes in the AV3V and were tested conscious and unrestrained. Dialysate was collected before, during, and following i.v. administration of ang II or phenylephrine which raised blood pressure 40-50 mmHg, or volume expansion with isotonic saline. Dialysate norepinephrine concentrations from these rats were compared to dialysate norepinephrine content from animals which received no treatment. Both i.v. infusion of ang II and isotonic volume expansion significantly increased dialysate norepinephrine concentration, while infusion of phenylephrine did not alter norepinephrine release in AV3V tissue. These data demonstrate that peripheral ang II and volume expansion selectively increase norepinephrine release in the AV3V region, and are consistent with the conclusion that activation of noradrenergic systems in the AV3V region contribute to cardiovascular and drinking responses evoked by peripheral ang II and to natriuresis following volume expansion.

Angiotensin II↗

PubMed1999

Sensitization of norepinephrine release in medial prefrontal cortex: effect of different chronic stress protocols.

Previously, we demonstrated that continuous exposure of rats to cold (5 degrees C) for 2-3 weeks potentiates the increase in extracellular norepinephrine in the medial prefrontal cortex produced by acute tail shock. In the present study, we used in vivo microdialysis to examine whether this sensitization of evoked norepinephrine release also occurs in the medial prefrontal cortex following exposure to other chronic stress protocols. Rats exposed to 30 min of intermittent foot shock (0.6 mA) each day for 14 days, did not exhibit a greater increase in extracellular norepinephrine in response to acute tail shock. To determine whether this discrepancy between cold exposure and foot shock might be related to differences in the nature or the pattern of exposure to the chronic stressor, we also examined the effect of intermittent exposure to cold or continuous exposure to a foot shock protocol on tail shock-evoked norepinephrine release. Sensitized norepinephrine release did not develop following either intermittent exposure to cold (5 degrees C; 4 h/day for 14 days) or continuous exposure to a foot shock protocol (0.6 mA trains at random intervals 24 h/day for 14 days), suggesting that both the nature of the stressor as well as the pattern of exposure to the chronic stressor play a role in the development of sensitized norepinephrine release.

Animals↗