Showing papers on "Norepinephrine (medication) published in 1994"
TL;DR: It is suggested that dopamine may cause an uncompensated increase in splanchnic oxygen requirements in septic patients and Norepinephrine, however, may have a more favorable hemodynamic profile and improve splan Schnic tissue oxygen utilization in sepsis.
Abstract: Objective. —To compare the effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in patients with hyperdynamic sepsis. Design. —A randomized short-term, interventional study. Setting. —An intensive care unit of a university hospital. Patients. —Twenty septic patients with a cardiac index greater than 3.2 L.min -1 .m -2 and either a mean arterial pressure (MAP) less than 60 mm Hg or a systemic vascular resistance index less than 1200 dyne.s.cm -5 .m -2 . Methods and Interventions. —Patients were randomized to receive an infusion of either dopamine or norepinephrine titrated to increase the MAP to greater than 75 mm Hg. The hemodynamic profile, oxygen delivery, oxygen consumption (determined by indirect calorimetry), and gastric intramucosal pH (pHi) (determined by gastric tonometry) were determined at baseline and after 3 hours of achieving the target MAP. Results. —Dopamine increased the MAP largely by increasing the cardiac index whereas norepinephrine increased the MAP by increasing the systemic vascular resistance index while maintaining the cardiac index. Although oxygen delivery and oxygen consumption increased in both groups of patients, the pHi increased significantly in those patients treated with norepinephrine whereas the pHi decreased significantly in those patients receiving dopamine ( P Conclusions. —This study suggests that dopamine may cause an uncompensated increase in splanchnic oxygen requirements in septic patients. Norepinephrine, however, may have a more favorable hemodynamic profile and improve splanchnic tissue oxygen utilization in sepsis. ( JAMA . 1994;272:1354-1357)
363 citations
TL;DR: It is indicated that a heavy-resistance strength-training program increases RMR in healthy older men, perhaps by increasing FFM and sympathetic nervous system activity.
Abstract: Resting metabolic rate (RMR) decreases with age, largely because of an age-related decline in fat-free mass (FFM). We hypothesized that a strength-training program capable of eliciting increases in...
311 citations
Journal Article•
TL;DR: M phi-associated norepinephrine appears to regulate LPS-induced TNF production in an autocrine fashion, suggesting a role for endogenous nore Alpinephrine in M phi.
Abstract: Evidence for the extraneuronal accumulation of norepinephrine has been demonstrated to occur in macrophage (M phi), yet the physiologic role of this system remains undefined. We have assessed the response of murine peritoneal M phi to adrenergic antagonists. We have also defined a physiologic role of a M phi-associated pool of the nonspecific adrenergic agonist norepinephrine. We investigated the constitutive involvement of alpha-adrenergic and beta-adrenergic receptors in LPS-induced TNF-alpha production. CFA-elicited M phis were incubated with LPS (1 microgram/ml) in the presence or absence of adrenergic agonists and/or antagonists. Although stimulation of alpha-adrenergic receptors increased TNF production and gene expression, beta-adrenergic receptors decreased it. Interestingly, when adrenergic antagonists along with LPS alone were added to M phi, they generated the response opposite to that produced by their suitable agonist, suggesting a role for endogenous norepinephrine in M phi. Thus, although alpha 2-adrenergic antagonists attenuated TNF production, beta-adrenergic antagonists augmented TNF expression in a concentration-dependent manner. Norepinephrine and epinephrine were found in M phi as determined by HPLC and LPS stimulation induced a significant decrease in their content. M phis were also incubated with LPS or medium only, washed, and then challenged 12 h later with LPS. When given a second LPS stimulation, M phis were found to have an increased response to alpha 2-adrenergic agonists and decreased response to alpha 2-adrenergic antagonists. Therefore, M phi-associated norepinephrine appears to regulate LPS-induced TNF production in an autocrine fashion.
265 citations
TL;DR: The view that TGF-beta 1, released by myocytes and acting in an autocrine and/or paracrine manner, is involved in myocardial remodeling by hypertrophic stimuli is supported.
Abstract: Transforming growth factor-beta 1 (TGF-beta 1) is a peptide growth factor that may play a role in the myocardial response to hypertrophic stimuli However, the cellular distribution, mechanism of induction, and source of increased TGF-beta 1 in response to hypertrophic stimuli are not known We tested the hypothesis that the cardiac myocyte responds to hypertrophic stimuli with the increased expression of TGF-beta 1 In adult rat ventricular myocardium freshly dissociated into myocyte and nonmyocyte cellular fractions, the preponderance of TGF-beta 1 mRNA visualized by Northern hybridization was in the nonmyocyte fraction Abdominal aortic constriction (7 d) and subcutaneous norepinephrine infusion (36 h) each caused ventricular hypertrophy associated with 31-fold and 38-fold increases, respectively, in TGF-beta 1 mRNA in the myocyte fraction, but had no effect on the level of TGF-beta 1 mRNA in the nonmyocyte fraction In ventricular myocytes, norepinephrine likewise caused a 41-fold increase in TGF-beta 1 mRNA associated with an increase in TGF-beta bioactivity This induction of TGF-beta 1 mRNA occurred at norepinephrine concentrations as low as 1 nM and was blocked by prazosin, but not propranolol NE did not increase the TGF-beta 1 mRNA level in nonmyocytes, primarily fibroblasts, cultured from neonatal rat ventricle Thus, the cardiac myocyte responds to two hypertrophic stimuli, pressure overload and norepinephrine, with the induction of TGF-beta 1 These data support the view that TGF-beta 1, released by myocytes and acting in an autocrine and/or paracrine manner, is involved in myocardial remodeling by hypertrophic stimuli
193 citations
TL;DR: Norepinephrine, at plasma levels easily attained during exercise, enhances platelet aggregability and platelet secretion in vivo in healthy humans.
Abstract: BACKGROUND Epinephrine and mental stress may, via platelet stimulation, enhance the risk of thrombus formation. Norepinephrine is more likely than epinephrine to activate platelets in vivo because of higher levels in plasma but is less well studied in this respect. The antiplatelet drug of choice for patients with coronary artery disease, aspirin, may be less effective during sympathoadrenal activation. We therefore investigated platelet responses in vivo to exogenous norepinephrine with and without aspirin pretreatment. METHODS AND RESULTS Platelet aggregability in vivo was assessed in 11 healthy male subjects, by filtragometry ex vivo (which reflects platelet aggregability in vivo) and by measurements of plasma beta-thromboglobulin (beta-TG, which reflects platelet secretion). Norepinephrine infusions elevated venous plasma norepinephrine from 1.5 to 4 and 15 nmol/L, respectively, and enhanced platelet aggregability (filtragometry) concentration dependently (P < .001). Platelet secretion (beta-TG levels) increased during high-dose infusion (P < .01). Aspirin pretreatment (500 mg orally 12 hours earlier) reduced the excretion of 11-dehydrothromboxane B2 by 62 +/- 5% (P < .001) and attenuated platelet aggregability at rest (P < .05) but not the effect of norepinephrine infusion on platelet aggregability. Conversely, resting plasma beta-TG levels and the urinary excretion of high-molecular-weight beta-TG were not altered by aspirin pretreatment, whereas the norepinephrine-induced increase in plasma beta-TG was abolished. CONCLUSIONS Norepinephrine, at plasma levels easily attained during exercise, enhances platelet aggregability and platelet secretion in vivo in healthy humans. Aspirin may be less effective as an antithrombotic drug during sympathoadrenal activation in humans.
184 citations
TL;DR: Exposure of the heart to either transient exogenous norepinephrine or endogenous release of norpinephrine and/or other catecholamines by tyramine can mimic the effects of ischemic preconditioning in rabbits.
Abstract: BACKGROUNDBrief episodes of ischemia induced by proximal coronary artery occlusion can precondition the myocardium. Whether other stressful stimuli have the potential to protect the myocardium from subsequent ischemia remains controversial.METHODS AND RESULTSTo study the hypothesis that transient alpha-adrenoceptor stimulation mimics preconditioning, for 5 minutes we administered 0.25 micrograms.kg-1.min-1 norepinephrine or saline 10 minutes before a 30-minute coronary occlusion and 4 hours of reperfusion in an in vivo rabbit model. The area of necrosis (AN) and area of risk (AR) were measured. We found that norepinephrine pretreatment caused a reduction in infarct size when compared with controls (AN/AR, 0.17 +/- 0.04 versus 0.31 +/- 0.04; P < .02). Ischemic preconditioning also reduced infarct size (AN/AR, 0.22 +/- 0.03). The protection observed with norepinephrine treatment was entirely eliminated by pretreatment with alpha-adrenergic blockade using prazosin (AN/AR, 0.42 +/- 0.06). Tyramine, an agent t...
151 citations
TL;DR: In this paper, the changes of circadian blood pressure patterns after thromboembolic and hemodynamic brain infarction and evaluated the relation between the change in blood pressure variation, infarct location, and activation of the autonomic nervous system after stroke.
Abstract: We investigated the changes of circadian blood pressure patterns after thromboembolic and hemodynamic brain infarction and evaluated the relation between circadian blood pressure variation, infarct location, and activation of the autonomic nervous system after thromboembolic stroke.
Repeated 24-hour blood pressure measurements were performed in 45 patients with proven first-ever brain infarctions of different origins. Evaluation of serum norepinephrine concentration, prolongation of the QT interval, and degree of cardiac arrhythmias were used to determine the extent of sympathetic activation after thromboembolic stroke.
Whereas circadian blood pressure variation was significantly increased after hemodynamic infarction compared with a control group (diastolic, -25.2 +/- 4.5% versus -13.8 +/- 6.5%; p < .005), a clearly reduced variation was observed after thromboembolic infarction (diastolic, -5.2 +/- 6.9%). Blood pressure variation was positively related to serum norepinephrine concentration (r = .79; P < .01) after thromboembolic infarction. Patients with involvement of the insular cortex showed a nocturnal rise of blood pressure significantly more frequently (66.7% versus 11.8%; P < .005) and had higher norepinephrine levels (66.7 +/- 110 pg/mL versus 290 +/- 178 pg/mL; P < .01) than patients without insular cortex infarction, indicating increased sympathetic activity. This was associated with a significantly more frequent occurrence of QT prolongation and cardiac arrhythmias.
The observed differences in circadian blood pressure patterns may (1) help to distinguish the pathophysiological basis of the stroke, (2) help to explain worsening in some cases of hemodynamic stroke, (3) confirm the importance of the insular cortex for sympathetic activation, and (4) identify subgroups of patients with increased risk of myocardial infarction and arrhythmia.
142 citations
TL;DR: The present study confirms the onset of a dramatic increase in cardiac norepinephrine release from myocardial nerve endings following brain death, and demonstrates the utility of the new cardiac microdialysis technique to assess changes in interstitial fluid content.
Abstract: Brain death is a pathophysiological condition associated with major hemodynamic changes, temporary myocardial ischemia, and histological damage of the heart. These modifications could be related to a major local release of norepinephrine from myocardial sympathetic nerve endings leading to norepinephrine cardiotoxicity. This study was designed to evaluate the utility of cardiac microdialysis to measure interstitial myocardial norepinephrine release resulting from brain death. The dialysis probe consisted in a 10 x 0.20-mm dialysis fiber with a 18,000 mol wt cutoff. Dialysis probes were implanted into the right and left ventricular walls of the beating heart in anesthetized pigs and perfused with Ringer solution at 2 microliters/min. Dialysate norepinephrine concentration was measured using HPLC with electrochemical detection. The relative recovery rate of norepinephrine in vivo was 34 +/- 4%. Interstitial fluid concentrations were obtained using the following formula: [C]interstitium = [C]dialysate/Recovery in vivo. After brain death, a transient increase in interstitial norepinephrine concentration was observed (from 0.74 +/- 0.20 to 4.50 +/- 0.60 ng/ml and 0.76 +/- 0.20 to 6.2 +/- 0.9 ng/ml in left and right ventricle, respectively, P < 0.01) which far exceeded plasma level increase (from 0.50 +/- 0.10 ng/ml to 0.91 +/- 0.20 ng/ml, P < 0.05). This increase in myocardial norepinephrine was, moreover, biphasic, with a second peak occurring 40 min after brain death. The present study confirms the onset of a dramatic increase in cardiac norepinephrine release from myocardial nerve endings following brain death, and demonstrate the utility of the new cardiac microdialysis technique to assess changes in interstitial fluid content.
138 citations
TL;DR: In this paper, background subtracted cyclic voltammetry at a scan rate of 800 V/s with carbon fiber microelectrodes has been used to detect and differentiate between epinephrine and norepinephrine.
Abstract: : Background-subtracted cyclic voltammetry at a scan rate of 800 V/s with carbon fiber microelectrodes has been used to detect and differentiate between epinephrine and norepinephrine. At very positive potentials (>l V vs. SSCE) in pH 7.4 aqueous buffer, a second oxidation wave is observed for epinephrine, a secondary amine. In contrast, the second oxidation wave is not observed for norepinephrine, a primary amine. The amplitude of the second wave for epinephrine is enhanced when the waveform employed does not allow reduction of the electrogenerated o-quinone back to epinephrine. This indicates that the oxidation process at the second wave must be preceded by adsorption of the o- quinone at the electrode surface. The temporal response of the method was investigated by iontophoretic ejection of catecholamine onto an electrode. The response time was found to be limited by the repetition rate of the cyclic voltammograms (16.7 ms in this work). This electrochemical technique was used to resolve catecholamine release from individual vesicles of cultured bovine adrenal medullary cells. Most of the adrenal medullary cells released either epinephrine or norepinephrine but 17% of the cells released mixtures of these two compounds. In these cells, each secretory vesicle appeared to contain either epinephrine or norepinephrine.
128 citations
TL;DR: Results are not consistent with the hypothesis of segmental sympathetic hyperactivity in the affected limb in sympathetically maintained pain and support a hypothesis of peripheral receptor upregulation with pathologic response to circulating catecholamines.
Abstract: Objective: To test the hypothesis that there is relative sympathetic hyperactivity in the affected limb in patients with sympathetically maintained pain syndromes by measuring serum norepinephrine and epinephrine in the affected versus the unaffected sides. Design: Venous pool samples were drawn just proximal to the affected area and from an identical site on the unaffected side. Serum norepinephrine and epinephrine were measured by high-pressure liquid chromatography with electrochemical detection. Subjects: Sixteen women and seven men with a mean age of 44.4 years diagnosed as having sympathetically maintained pain on the basis of a positive response to paravertebral block and a criteria-based diagnostic scheme. Results: The serum norepinephrine level was significantly lower in the affected limbs than the unaffected limbs (p = 0.024). The serum epinephrine level was not significantly different. Conclusions: These results are not consistent with the hypothesis of segmental sympathetic hyperactivity in the affected limb in sympathetically maintained pain and support a hypothesis of peripheral receptor upregulation with pathologic response to circulating catecholamines. Other possible explanations are discussed.
124 citations
TL;DR: Baseline preference significantly influenced dietary selection after all six experimental procedures studied in regimen I and after NPY, NE, 48 h food deprivation, and chronic dietary restriction in regimen II (covariate P < 0.05).
Abstract: The orexigenic agents morphine, neuropeptide Y (NPY), and norepinephrine (NE) and deprivation have been reported to induce selection of specific macronutrients: fat, carbohydrate (CHO), CHO, and fa...
TL;DR: The results imply that it is predominantly or solely the beta 3-receptor that is coupled to thermogenesis, and it is via this beta-adrenergic receptor that not only norepinephrine but also CGP-12177 and BRL-37344 induce thermogenesis.
Abstract: The possible significance of the coexisting beta 1-, beta 2-, and beta 3-adrenoceptors in brown adipose tissue for the thermogenic response was investigated. Oxygen consumption of isolated hamster brown fat cells was analyzed as a measure of thermogenesis. Thermogenesis could be evoked not only by the physiological agent norepinephrine but also by BRL-37344 and CGP-12177. No evidence for biphasic inhibition curves was found with either the selective beta 1-antagonist ICI-89406, the beta 2-antagonist ICI-118551, or the beta 1/beta 2-nonselective beta-antagonist propranolol against 1 microM norepinephrine; pI50 (the negative logarithm of the inhibitory constant for an antagonist, as estimated from the dose-response curve for an antagonist vs. a constant agonist concentration) values for ICI-89406 and ICI-118551 were very low (4-5), implying nonselective inhibition; the pI50 for propranolol was approximately 6 (as expected for the beta 3-receptor). Even with suboptimal norepinephrine, no biphasic inhibition was found. CGP-12177 at concentrations where it is primarily an antagonist to the beta 1-receptor did not influence the dose-response curve for either norepinephrine or BRL-37344. BRL-37344- or CGP-12177-induced thermogenesis was inhibited by the beta-antagonists in a manner similar to norepinephrine-induced thermogenesis. Schild plots for propranolol inhibition of norepinephrine-, isoprenaline-, BRL-37344- and CGP-12177-induced thermogenesis yielded similar pA2 (the negative logarithm of the inhibitory constant for an antagonist, as calculated from a series of agonist dose-response curves at different antagonist concentrations) (approximately 5.5), for interaction with either agonist, implying that the same receptor was stimulated by all agonists. Thus, despite the fact that different beta-receptor subtypes coexist in the tissue, we find no evidence for the participation of beta 1- or beta 2-receptors in the thermogenic response. Within the resolution of the experiments, the results therefore imply that it is predominantly or solely the beta 3-receptor that is coupled to thermogenesis, and it is via this beta-adrenergic receptor that not only norepinephrine but also CGP-12177 and BRL-37344 induce thermogenesis.
TL;DR: The hypothesis that active muscle movement in lightly anesthetized subjects has an effect on the brain that is mediated in part by muscle afferent receptors is supported.
Abstract: Background: Afferentation theory predicts that agents or maneuvers that stimulate muscle stretch receptors (i.e., muscle afferents) will produce cerebral stimulation. From this theory it follows that, regardless of the source (e. g., drug effect, active muscle movement), increases in stretch receptor activity should result in a similar effect on the brain. The present study tested the hypothesis that active muscle movement in lightly anesthetized subjects would result in cerebral stimulation. Methods: Studies were conducted in six dogs who were lightly anesthetized with halothane (0.70% end-expired). The following physiologic variables were quantified before and for 6 min after the initiation of a standardized (1-min duration) noxious stimulus to the trachea and the skin overlying the hind limb: cerebral blood flow, cerebral metabolic rate for oxygen (CMRO 2 ), cerebral perfusion pressure, cerebral vascular resistance, electroencephalogram activity, electromyogram activity, arterial carbon dioxide partial pressure (PaCO 2 ), central venous Pressure, and serum epinephrine and norepinephrine concentrations. Response to stimulation was evaluated initially in unparalyzed dogs and later was evaluated in the same dogs after they were paralyzed with intravenous Pancuronium (0.2 mg/kg). Results: in unparalyzed dogs, stimulation produced episodes of coughing plus head and limb movement during the 6-min study period. Accompanying the movement was activation of the electromyogram, an increase in electroencephalogram frequency, and a reduction in electroencephalogram amplitude. There also was a 35% increase in cerebral blood flow, a 25% decrease in cerebral vascular resistance, and a 7% increase in CMRO 2 versus the baseline values for each variable. There were no significant increases in either cerebral perfusion pressure, central venous pressure, PaCO 2 , or serum norepinephrine concentration to account for the cerebral effects; however, serum epinephrine concentrations increased by 61%. In pancuronium-paralyzed dogs, noxious stimulation resulted in a 5% increase in cerebral blood flow, a 7% decrease in cerebral vascular resistance, and an 5% increase in CMRO 2 versus baseline levels. Electroencephalogram frequency was increased, but amplitude was unchanged. Central venous pressure, electromyogram activity, and serum norepinephrine concentration were unaffected. The serum epinephrine response was similar to that observed when the dogs were not paralyzed. Conclusions: These data support the hypothesis that active muscle movement in lightly anesthetized subjects has an effect on the brain that is mediated in part by muscle afferent receptors. This cerebral response was manifested as electroencephalogram activation, cerebral vasodilation unrelated to central venous pressure changes, and an increase in cerebral blood flow greater than that required to meet metabolic demands. Paralysis with pancuronium abolished movement induced by stimulation (and, thus, the muscle afferent response) and also attenuated the cerebral blood flow, cerebral vascular resistance, and electroencephalogram responses
TL;DR: In this article, the ontogeny of THRH and NE potentiation of inspiratory-related hypoglossal (XII) motor nerve discharge was studied in medullary slices from P0-3.1.
Abstract: 1. The ontogeny of thyrotropin-releasing hormone (TRH) and norepinephrine (NE) potentiation of inspiratory-related hypoglossal (XII) motor nerve discharge was studied in medullary slices from P0–3,...
TL;DR: D dorsal hand vein responses to local infusion of endothelin-1 and norepinephrine in 12 patients with essential hypertension who had never received treatment and in 12 age and sex matched normotensive control subjects are investigated.
Abstract: Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide. Although circulating concentrations are not increased in essential hypertension, enhanced sensitivity to endothelin-1 has been observed in animal models of hypertension. We investigated dorsal hand vein responses to local infusion of endothelin-1 and norepinephrine in 12 patients with essential hypertension who had never received treatment and in 12 age and sex matched normotensive control subjects. The maximal venoconstriction and the geometric mean of the dose of norepinephrine that caused 50% of maximal venoconstriction were similar in hypertensive (mean +/- SE; 80 +/- 4%; 31 +/- 8 pmol/min) and normotensive subjects (87 +/- 5%, 22 +/- 9 pmol/min). In contrast, mean venoconstriction to endothelin-1 was significantly greater in hypertensive (49 +/- 5%) than in normotensive subjects (27 +/- 2%; P = 0.004). Sympathetically mediated venoconstriction elicited by deep breath was substantially potentiated by endothelin-1 in hypertensive (67 +/- 7% at 90 min) but not normotensive subjects (11 +/- 3% at 90 min; P = 0.001). Venoconstriction to endothelin-1 correlated positively with mean arterial pressure in the hypertensive subjects (r = 0.82; p = 0.001) but negatively in the normotensive subjects (r = -0.58; p = 0.047). Endothelin-1 may contribute to the reduction of venous compliance occurring in the early stages of essential hypertension and to the altered systemic hemodynamics in this condition.
Journal Article•
TL;DR: It is found that prejunctional histamine H3-receptors modulate the depolarization-dependent norepinephrine release from sympathetic nerve endings in the guinea pig myocardium.
Abstract: Discovered as inhibitory autoreceptors in central histaminergic pathways, histamine H3-receptors may also modulate peripheral cholinergic and central adrenergic function. Recently, H3-receptors were reported to inhibit adrenergic inotropic responses in guinea pig atria, possibly at prejunctional sites. We have assessed whether the H3-mediated modulation of cardiac adrenergic activities results from a reduction in norepinephrine release. We have found that (R) alpha-methylhistamine, the selective histamine H3-receptor agonist, attenuates the inotropic and chronotropic response of isolated guinea pig atria to transmural stimulation of adrenergic nerve endings. This attenuation was associated with a marked reduction in endogenous norepinephrine release. In contrast (R) alpha-methylhistamine did not modify the chronotropic effect of exogenous norepinephrine. The attenuation of adrenergic responses by (R) alpha-methylhistamine was 1) prevented by thioperamide, the selective H3-receptor antagonist; 2) attenuated by pertussis-toxin pretreatment and 3) potentiated by the N-type Ca(++)-channel blocker omega-conotoxin, which also potentiated the sympathetic modulatory effects of adrenergic-alpha 2 and adenosine-A1 receptor agonists. Our findings indicate that prejunctional histamine H3-receptors modulate the depolarization-dependent norepinephrine release from sympathetic nerve endings in the guinea pig myocardium. These receptors are probably coupled to a pertussis-toxin-sensitive Gi/Go protein and probably effect a reduction in Ca++ current. We have previously reported that sympathetic stimulation elicits a frequency-dependent release of cardiac histamine, whereas others had found that adrenergic activity regulates histamine's rapid turnover pool. Accordingly, presynaptic H3-receptors are likely to serve a modulatory role in cardiac adrenergic function.
Journal Article•
TL;DR: Diaspirin cross-linked hemoglobin (DCLHB) is a promising hemoglobin-based oxygen-carrying resuscitative solution that alters the responsiveness of peripheral vascular adrenoceptors and the effect of DCLHb pretreatment on the blood pressure and heart rate responses of adrenergic agonists was studied.
TL;DR: The results suggest that the intraperitoneal injection of IL-1 beta facilitates noradrenaline release in the spleen through activation of the sympathetic nerve, and the increased sympathetic activity is, at least in part, due to the excitation of neurons containing CRF in the brain.
Abstract: The purpose of this study was to investigate whether an intraperitoneal injection of interleukin-1β (IL-1β) affects noradrenaline release in the spleen through its action on the brain of conscious rats. An in vivo microdialysis technique consisting of highperformance liquid chromatography with electrochemical detection was used for chronic monitoring of the splenic noradrenaline. The perfusion of a high concentration of K+ Ringer solution through the microdialysis probe significantly increased the concentration of noradrenaline in the spleen, while a perfusion of either Ca2+-free or tetrodotoxin-containing Ringer solution decreased the noradrenaline level in the dialysate. These results indicate that the noradrenaline recovered in the splenic dialysate is mainly derived from the nerve terminals of the splenic sympathetic nerve. The intraperitoneal injection of IL-1β (100 ng/kg) produced an immediate and significant increase in the noradrenaline levels in the spleen. The increased level reached a maximum level 40 min after injection and then gradually returned to the basal level. An intracerebroventricular (ICV) injection of a corticotropin-releasing factor (CRF) antagonist (α-helical CRF9-41, 30 μg) significantly attenuated the IL-1β-induced increase in the noradrenaline release. An ICV injection of CRF (2 μg) also caused a significant increase in splenic noradrenaline, which showed two distinct peaks at 20 and 140 min, respectively. These results suggest that the intraperitoneal injection of IL-1β facilitates noradrenaline release in the spleen through activation of the sympathetic nerve, and the increased sympathetic activity is, at least in part, due to the excitation of neurons containing CRF in the brain.
TL;DR: The arteriolar wall thickness and left ventricular mass as well as the vascular response to norepinephrine and acetylcholine in spontaneously hypertensive rats (SHR), before and after the development of hypertension, as compared to age-matched normotensive Wistar-Kyoto rats (WKY).
Journal Article•
TL;DR: In this paper, the changes of circadian blood pressure patterns after thromboembolic and hemodynamic brain infarction were investigated and the relation between the changes and infarct location and activation of the autonomic nervous system was evaluated.
Abstract: We investigated the changes of circadian blood pressure patterns after thromboembolic and hemodynamic brain infarction and evaluated the relation between circadian blood pressure variation, infarct location, and activation of the autonomic nervous system after thromboembolic stroke.Repeated 24-hour blood pressure measurements were performed in 45 patients with proven first-ever brain infarctions of different origins. Evaluation of serum norepinephrine concentration, prolongation of the QT interval, and degree of cardiac arrhythmias were used to determine the extent of sympathetic activation after thromboembolic stroke.Whereas circadian blood pressure variation was significantly increased after hemodynamic infarction compared with a control group (diastolic, -25.2 +/- 4.5% versus -13.8 +/- 6.5%; p < .005), a clearly reduced variation was observed after thromboembolic infarction (diastolic, -5.2 +/- 6.9%). Blood pressure variation was positively related to serum norepinephrine concentration (r = .79; P < .0...
TL;DR: The results suggest that Ang-(1-7), like Ang II, could have a neuromodulatory function in rat atria via activation of specific angiotensin receptor subtypes, which could be the subtype 1 angiotENSin receptor for Ang II and subtypes 1 and 2 for Ang-( 1-7).
Abstract: We examined the effects of angiotensin II (Ang II) and Ang-(1-7) on the release of [3H]norepinephrine elicited by nerve stimulation (2 Hz, 0.5 millisecond, for 2 minutes) in rat atria isolated with their cardioaccelerans nerves. The stimulation-induced release of [3H]norepinephrine was increased 50% by 3 x 10(-8) mol/L of either peptide. No further increase in [3H]norepinephrine release was observed with peptide concentrations up to 3 x 10(-7) mol/L. This effect was completely blocked by the nonselective angiotensin receptor antagonist saralasin (1 x 10(-7) mol/L). The type 1 angiotensin receptor antagonist DuP 753 (1 x 10(-6) mol/L) entirely prevented the increases in [3H]norepinephrine caused by Ang II and Ang-(1-7). On the other hand, the type 2 angiotensin receptor antagonist PD 123319 (1 x 10(-6) mol/L) prevented the increase in [3H]norepinephrine release elicited by Ang-(1-7) but not by Ang II. These results suggest that Ang-(1-7), like Ang II, could have a neuromodulatory function in rat atria via activation of specific angiotensin receptor subtypes, which could be the subtype 1 angiotensin receptor for Ang II and subtypes 1 and 2 for Ang-(1-7).
Journal Article•
TL;DR: It is reported that in the presence of H1- and H2- receptor blockers, histamine significantly inhibits the tachycardia and norepinephrine release elicited by sympathetic nerve stimulation is isolated guinea pig hearts, an effect prevented by the H3 antagonist, thioperamide.
Abstract: We had previously found that histamine H3- receptors are negatively coupled to norepinephrine exocytosis in atrial tissue. We report here that in the presence of H1- and H2- receptor blockers, histamine significantly inhibits the tachycardia and norepinephrine release elicited by sympathetic nerve stimulation is isolated guinea pig hearts, an effect prevented by the H3 antagonist, thioperamide. Sympathetic nerve stimulation also caused a 1.5-fold increase in histamine overflow, which was insufficient to activate H3 receptors because thioperamide affected neither the tachycardia nor the norepinephrine release. Hence. We questioned whether H3 receptors become activated when adrenergic activity is greatly enhanced, as in myocardial ischemia. Guinea pig hearts underwent 10-min global ischemia. At reperfusion, norepinephrine exocytosis was markedly augmented and was associated with a 3.5-fold increase in histamine overflow. (R)alpha-methylhistamine, an H3 agonist, did not modify norepinephrine release, whereas thioperamide doubled it. Thus, in physiologic conditions, cardiac H3 receptors are quiescent, yet available for activation by exogenous ligands. In contrast, in the ischemic myocardium, H3 receptors appear to be fully activated by an endogenous ligand, probably histamine. Hence, cardiac H3 receptors may play an important role by negatively modulating exocytotic norepinephrine release associated with ischemic states.
Journal Article•
TL;DR: A more favorable pharmacological profile is suggested for HEP as a potential drug for Alzheimer disease, as compared to PHY, because of its longer lasting inhibition of cholinesterase and more prolonged elevation of ACh in cerebral cortex than PHY.
Abstract: A microdialysis technique was used to investigate the effect of physostigmine (PHY) and heptylphysostigmine (HEP), administered systemically or locally, on the extracellular levels of acetyl-choline (ACh), norepinephrine, dopamine and 5-hydroxytryptamine in the cerebral cortex of the rat. Levels of these neurotransmitters in dialysates were assayed simultaneously with two different high pressure liquid chromatography systems. No cholinesterase inhibitor was added into the probe to increase detection of ACh after systemic administration. Cholinesterase inhibition and its relation to ACh levels were also studied. Systemic administration of two doses of cholinesterase inhibitor [PHY (30 and 300 micrograms/kg) and HEP (2 and 5 mg/kg)] produced a dose-dependent increase in ACh levels. Local perfusion of these drugs through the probe elicited a strong increase in extracellular ACh. HEP produced a longer lasting inhibition of cholinesterase and a more prolonged elevation of ACh in cerebral cortex than PHY. After systemic administration of PHY (both doses), we observed a significant increase of norepinephrine levels. This effect was weaker after HEP. Local administration through the probe did not modify norepinephrine concentration. Dopamine levels were also increased after systemic administration. ONly HEP perfused into the probe elicited a significant increase in extracellular dopamine. Systemic or local administration did not modify 5-hydroxytryptamine levels. These observations suggest a more favorable pharmacological profile for HEP as a potential drug for Alzheimer disease, as compared to PHY.
TL;DR: TNF-induced regulation of [3H]norepinephrine release appears to be associated with an alteration of alpha 2-adrenergic receptor responsiveness, and the reversal in presynaptic TNF responsiveness after 14 days of tricyclic antidepressant drug administration is described.
TL;DR: Enzymes The core-specific lysosomal a(1-6)-mannosidase activity depends on aspartamidohydrolase activity and substrate analogues as probes of the catalytic mechanism of L-mandelate dehydrogenase from Rhodotorula graminis are studied.
Abstract: Enzymes The core-specific lysosomal a(1-6)-mannosidase activity depends on aspartamidohydrolase activity Phosphorylation of adenosine in renal brush-border membrane vesicles by an exchange reaction catalysed by adenosine kinase Purification and characterization of phosphatidylinositol synthase from human placenta NADPH-cytochrome c reductase from human neutrophil membranes: purification, characterization and localization The amino acid sequence of the small monomeric phosphoglycerate mutase from the fission yeast Schizosaccharomyces pombe Substrate analogues as probes of the catalytic mechanism of L-mandelate dehydrogenase from Rhodotorula graminis
TL;DR: The results show that IL-6 exerts a dual effect on norepinephrine release, and there is synergism between IL-1 beta andIL-6 resulting in suppression of nore Alpinephrine release.
TL;DR: The data imply that changes in concentrations of circulating catecholamines cannot be unequivocally labeled as indexes of an altered sympathoadrenal involvement in short-term cardiovascular control.
Abstract: Spectral analysis of fluctuations in heart rate (HR) and arterial blood pressure (BP) during a 6-h infusion of epinephrine (15 ng.kg-1.min-1) or norepinephrine (30 ng.kg-1.min-1) in 10 normotensive...
TL;DR: Plasma norepinephrine concentration increases with altitude exposure while maximal heart rate (HR) and chronotropic response to isoproterenol (IP) are blunted and downregulation of cardiac beta-adrenergic receptors (beta-AR) has been evoked to explain this phenomenon.
Abstract: Plasma norepinephrine (NE) concentration increases with altitude exposure while maximal heart rate (HR) and chronotropic response to isoproterenol (IP) are blunted. Downregulation of cardiac beta-a...
TL;DR: It is demonstrated that sensitivity to exogenous norepinephrine is not different in essential hypertension but that there is defective endothelium-dependent dilatation, suggesting a contributory role for endot Helium dysfunction in human essential hypertension.
Abstract: To simulate in vivo conditions as closely as possible to in vitro conditions, we examined the morphological and functional characteristics of isolated human subcutaneous small arteries from 17 essential hypertensive patients and 14 normotensive control subjects using a perfusion myograph. Vessel segments were cannulated and exposed to conditions of constant flow and pressure. The ratio of media thickness to lumen diameter in arteries from hypertensive patients increased significantly. With the endothelium intact, sensitivity to extraluminally applied norepinephrine was not different, and this was not affected by inhibition of neuronal amine uptake with cocaine. After removal of the endothelium, sensitivity to norepinephrine was augmented in normotensive vessels to a greater extent than in hypertensive vessels. Endothelium-dependent relaxation to acetylcholine was significantly reduced in arteries from hypertensive patients, but endothelium-independent relaxation to sodium nitroprusside was not different from that observed in vessels from normotensive control subjects. These data demonstrate that sensitivity to exogenous norepinephrine is not different in essential hypertension but that there is defective endothelium-dependent dilatation, suggesting a contributory role for endothelium dysfunction in human essential hypertension.
Journal Article•
TL;DR: Evidence is extended that duloxetine inhibits serotonin and norepinephrine transporters in vivo, actions that may lead to therapeutic efficacy in mental depression.
Abstract: Duloxetine, (+)-N-methyl-3-(1-naphthalenyloxy)-2-thiophenepropanamine, is an inhibitor of the serotonin and norepinephrine neuronal transporters (Wong et al., 1993). In mice, duloxetine antagonized the depletion of brain serotonin by p-chloroamphetamine (ED50 = 2.5 mg/kg, i.p.) and the depletion of heart norepinephrine by 6-hydroxydopamine (ED50 = 1.1 mg/kg, i.p.). Brain concentrations of 5-hydroxyindoleacetic acid were decreased by duloxetine at 2 hr after doses of 1, 3 and 10 mg/kg and at 1 to 8 hr (but not 24 hr) after a 10 mg/kg i.p. dose of duloxetine. Duloxetine antagonized norepinephrine depletion in frontal cortex, but not dopamine depletion in striatum, after treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In rats, duloxetine decreased brain 5-hydroxyindoleacetic acid dose-dependently for up to 8 hr and decreased serotonin turnover measured by the accumulation of 5-hydroxytryptophan in rat hypothalamus after decarboxylase inhibition. In rats, duloxetine antagonized the depletion of brain serotonin by p-chloramphetamine and the depletion of norepinephrine and epinephrine in hypothalamus after i.c.v. injection of 6-hydroxydopamine. In vitro, duloxetine had little effect on either type A (serotonin as substrate) or type B (phenylethylamine as substrate) monoamine oxidase, IC50 concentrations being above 10(-5) M. These data extend evidence that duloxetine inhibits serotonin and norepinephrine transporters in vivo, actions that may lead to therapeutic efficacy in mental depression.