scholarly journals Blockade of the sympathetic nervous system degrades ligament in a rat MCL model

2004 ◽  
Vol 96 (2) ◽  
pp. 711-718 ◽  
Author(s):  
Kelley W. Dwyer ◽  
Paolo P. Provenzano ◽  
Peter Muir ◽  
Wilmot B. Valhmu ◽  
Ray Vanderby
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Plasma Concentrations ◽  
Cathepsin K ◽  
Cysteine Proteases ◽  
Collagenolytic Activity ◽  
Tartrate Resistant Acid Phosphatase ◽  
Real Time Quantitative Pcr ◽  
Osmotic Pumps ◽  
Sympathetic Nervous

We hypothesize that blockade of the sympathetic nervous system degrades ligament. We tested this hypothesis in a rat medial collateral ligament (MCL) model. Fifteen animals were treated for 10 days with the sympathetic chemotoxin guanethidine using osmotic pumps, whereas 15 control rats received pumps containing saline. A reduction in plasma concentrations of norepinephrine in the guanethidine rats indicated a significant decrease in sympathetic nerve activity. Vasoactive intestinal peptide and neuropeptide Y were decreased in MCLs from guanethidine animals, as quantified by radioimmunoassays. Tissue vascularity was substantially increased in guanethidine MCLs, whereas mechanical properties were significantly decreased. Proteases, such as matrix metalloproteinases (MMP) and cysteine proteases, play a major role in ligament degradation. The proteases MMP-13, cathepsin K, and tartrate-resistant acid phosphatase (TRAP) have collagenolytic activity and have been shown in rat ligament tissues. To determine whether the degradation seen in this study was due to protease activity, we determined the expression of these enzymes in control and treated MCLs. Real-time quantitative PCR revealed that guanethidine treatment increased expression of MMP-13 and cathepsin K mRNAs, although overall expression levels of MMP-13 and TRAP were relatively low. Histology also identified increases in TRAP and cathepsin K, but not MMP-13, in guanethidine-treated tissues. Results support our hypothesis that blockade of the sympathetic nervous system substantially degrades ligament.

scholarly journals Interleukin-1 receptor antagonist treatment in acute ischaemic stroke does not alter systemic markers of anti-microbial defence

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1039
Author(s):  
Laura McCulloch ◽  
Stuart M. Allan ◽  
Hedley C. Emsley ◽  
Craig J. Smith ◽  
Barry W. McColl
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Receptor Antagonist ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Plasma Concentrations ◽  
Classical Pathway ◽  
Stroke Patients ◽  
Complement Components ◽  
Sympathetic Nervous

Background: Blockade of the cytokine interleukin-1 (IL-1) with IL-1 receptor antagonist (IL-1Ra) is a candidate treatment for stroke entering phase II/III trials, which acts by inhibiting harmful inflammatory responses.  Infection is a common complication after stroke that significantly worsens outcome and is related to stroke-induced deficits in systemic immune function thought to be mediated by the sympathetic nervous system.  Therefore, immunomodulatory treatments for stroke, such as IL-1Ra, carry a risk of aggravating stroke-associated infection. Our primary objective was to determine if factors associated with antibody-mediated antibacterial defences were further compromised in patients treated with IL-1Ra after stroke. Methods: We assessed plasma concentrations of immunoglobulin isotypes and complement components in stroke patients treated with IL-1Ra or placebo and untreated non-stroke controls using multiplex protein assays. Activation of the sympathetic nervous system (SNS) was determined by measuring noradrenaline, a major SNS mediator. Results:  There were significantly lower plasma concentrations of IgM, IgA, IgG1 and IgG4 in stroke-patients compared to non-stroke controls, however there were no differences between stroke patients treated with placebo or IL-1Ra. Concentrations of complement components associated with the classical pathway  were increased and those associated with the alternative pathways decreased in stroke patients, neither being affected by treatment with IL-1Ra.  Noradrenaline concentrations were increased after stroke in both placebo and IL-1Ra-treated stroke patients compared to non-stroke controls.  Conclusion: These data show treatment with IL-1Ra after stroke does not alter circulating immunoglobulin and complement concentrations and is therefore unlikely to further aggravate stroke-associated infection susceptibility through reduced availability of these key anti-microbial mediators.

Oxygen consumption after massive sympathetic nervous system discharge

1989 ◽  
Vol 256 (3) ◽  
pp. E345-E351 ◽  
Author(s):  
S. A. Lang ◽  
M. B. Maron ◽  
S. A. Signs
Keyword(s):  
Nervous System ◽  
Oxygen Consumption ◽  
Sympathetic Nervous System ◽  
Plasma Concentrations ◽  
Neurogenic Pulmonary Edema ◽  
O2 Consumption ◽  
Anesthetized Dogs ◽  
Sympathetic Nervous ◽  
O2 Supply ◽  
Alpha Chloralose

We evaluated the possibility that massive, sympathetic nervous system (SNS) activation [as may precede the development of neurogenic pulmonary edema (NPE)] increases O2 demand. O2 consumption (VO2) and plasma concentrations of the calorigenic agents, epinephrine (EPI) and norepinephrine (NE) were measured in alpha-chloralose-anesthetized dogs under control conditions and for 3 h after the administration of either 1) intracisternal (ic) veratrine to activate the SNS, 2) intravenous (iv) veratrine, 3) ic saline, or 4) ic veratrine, after clamping the adrenal blood vessels. VO2 increased 31.7 +/- 3.6% (SE), and EPI and NE increased to, respectively, 30,853 +/- 8,347 and 8,176 +/- 2,104 pg/ml in the ic veratrine group. No increases in VO2 and EPI and attenuated increases in NE were observed in the ic veratrine animals with clamped adrenals. No significant increases in VO2 or catecholamine concentrations were observed after ic saline or iv veratrine administration. These data suggest that the elevated VO2 may have been mediated by adrenal catecholamines and that an increased metabolic rate may complicate the ability of patients with severe NPE to balance O2 supply with demand.

scholarly journals Interleukin-1 receptor antagonist treatment in acute ischaemic stroke does not alter systemic markers of anti-microbial defence

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1039
Author(s):  
Laura McCulloch ◽  
Stuart M. Allan ◽  
Hedley C. Emsley ◽  
Craig J. Smith ◽  
Barry W. McColl
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Receptor Antagonist ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Plasma Concentrations ◽  
Classical Pathway ◽  
Stroke Patients ◽  
Complement Components ◽  
Sympathetic Nervous

Background: Blockade of the cytokine interleukin-1 (IL-1) with IL-1 receptor antagonist (IL-1Ra) is a candidate treatment for stroke entering phase II/III trials, which acts by inhibiting harmful inflammatory responses.  Infection is a common complication after stroke that significantly worsens outcome and is related to stroke-induced deficits in systemic immune function thought to be mediated by the sympathetic nervous system.  Therefore, immunomodulatory treatments for stroke, such as IL-1Ra, carry a risk of aggravating stroke-associated infection. Our primary objective was to determine if factors associated with antibody-mediated antibacterial defences were further compromised in patients treated with IL-1Ra after stroke. Methods: We assessed plasma concentrations of immunoglobulin isotypes and complement components in stroke patients treated with IL-1Ra or placebo and untreated non-stroke controls using multiplex protein assays. Activation of the sympathetic nervous system (SNS) was determined by measuring noradrenaline, a major SNS mediator. Results:  There were significantly lower plasma concentrations of IgM, IgA, IgG1 and IgG4 in stroke-patients compared to non-stroke controls, however there were no differences between stroke patients treated with placebo or IL-1Ra. Concentrations of complement components associated with the classical pathway  were increased and those associated with the alternative pathways decreased in stroke patients, neither being affected by treatment with IL-1Ra.  Noradrenaline concentrations were increased after stroke in both placebo and IL-1Ra-treated stroke patients compared to non-stroke controls.  Conclusion: These data show treatment with IL-1Ra after stroke does not alter circulating immunoglobulin and complement concentrations and is therefore unlikely to further aggravate stroke-associated infection susceptibility through altered availability of these key anti-microbial mediators.

Sympathetic nervous system and blood pressure maintenance in the Brattleboro DI rat

1986 ◽  
Vol 250 (5) ◽  
pp. R770-R775 ◽  
Author(s):  
J. L. Williams ◽  
M. D. Johnson
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Bolus Injection ◽  
Plasma Concentrations ◽  
Sympathetic Function ◽  
Unstressed State ◽  
Basal Plasma ◽  
Sympathetic Nervous

Experiments were performed to determine the functional role of the sympathetic nervous system (SNS) in blood pressure regulation in Brattleboro diabetes insipidus (DI) rats and to determine the effects of synthetic arginine vasopressin (AVP) on sympathetic function in DI rats. The experiments were conducted in male age-matched Long-Evans (LE) and DI rats in the conscious unstressed state. Mean arterial pressure (MAP) and heart rate were similar in conscious unstressed LE and DI rats, but basal plasma concentrations of norepinephrine (NE) and epinephrine (E) were elevated in DI rats compared with LE rats. An intra-arterial bolus injection of hexamethonium (30 mg/kg) resulted in greater reductions of MAP in DI rats (-62 +/- 5 mmHg) than in LE rats (-42 +/- 7 mmHg; P less than 0.05). Administration of AVP to DI rats by osmotic minipump reduced plasma NE concentration in DI rats to a level not different from that in LE rats, but E concentration remained elevated. AVP administration to DI rats also reduced the hexamethonium-induced fall in MAP in these animals (-47 +/- 7 mmHg) to a level not different from that in LE rats. We conclude that the SNS plays a greater role in blood pressure maintenance in conscious DI rats than in LE rats and that AVP administration can normalize plasma NE concentration and the contribution of the SNS to blood pressure maintenance in these animals.

Conditioning of Rats to Tumbling Trauma by Electroconvulsive Shock

1957 ◽  
Vol 189 (3) ◽  
pp. 504-508 ◽  
Author(s):  
Robert L. Griswold ◽  
Irving Gray
Keyword(s):  
Nervous System ◽  
Electrical Stimulation ◽  
Sympathetic Nervous System ◽  
Plasma Concentrations ◽  
Marked Rise ◽  
Lethal Effects ◽  
Rapid Fall ◽  
Sympathetic Nervous ◽  
Previous Series ◽  
Stimulation Of

Rats were made relatively resistant to the lethal effects of tumbling trauma by a previous series of electroconvulsive shocks (ECS). ECS causes an immediate marked rise in the plasma concentrations of adrenaline and noradrenaline, as a result of the electrical stimulation of the sympathetic nervous system. The plasma concentrations of adrenaline and noradrenaline, which are elevated in response to trauma, show a more rapid fall after termination of trauma in the ECS-conditioned animals than in controls. There is no significant alteration in the sensitivity of ECS-conditioned rats to toxic doses of adrenaline and noradrenaline. It is thought that ECS-conditioning, and probably also the conventional drum-conditioning, are brought about by a diminished reactivity of the sympathetic nervous system after its repeated stimulation.

Activation of renal sympathetic outflow by intracisternal hypertonic NaCl in dogs

1989 ◽  
Vol 256 (2) ◽  
pp. H411-H416
Author(s):  
I. Abe ◽  
D. B. Averill ◽  
C. M. Ferrario
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Brain Stem ◽  
Plasma Concentrations ◽  
Base Line ◽  
Cisterna Magna ◽  
Arterial Blood ◽  
Sympathetic Nervous ◽  
Lower Brain Stem ◽  
Renal Sympathetic

The neurohormonal and sympathetic nervous system responses to injection of hypertonic NaCl (1.5 M) into the cisterna magna were investigated in morphine-pentobarbital-anesthetized dogs (n = 8). Mean arterial blood pressure (MAP), heart rate (HR), and integrated efferent renal sympathetic nerve activity (ERSNA) were recorded, and blood samples were taken for the determination of plasma concentrations of epinephrine (Epi), norepinephrine (NE), arginine vasopressin (AVP), osmolality, plasma renin activity (PRA), and serum sodium and potassium. By 2 min after injection of hypertonic NaCl into the cisterna magna, significant increases were observed for MAP (+47 +/- 5 mmHg, P less than 0.01), HR (+59 +/- 11 beats/min, P less than 0.01), and ERSNA (+47 +/- 16%, P less than 0.01) above base line. The increased activity of the sympathetic nervous system was not accompanied by changes in PRA, Epi, NE, or AVP. Hypertonic NaCl was injected into the cisterna magna of six dogs before and after intravenous administration of the AVP antagonist [d(CH2)5Tyr(Me)]AVP. The time course for increases in MAP, HR, and ERSNA was not affected by AVP blockade. Subsequent administration of hexamethonium chloride abolished the pressor, tachycardic, and ERSNA responses elicited by cisterna magna injection of hypertonic NaCl. These experiments indicate that hypertonic NaCl acts at the lower brain stem to activate the sympathetic nervous system. Further, the pressor and tachycardic responses evoked by hypertonic NaCl acting at the lower brain stem do not appear to involve the hypothalamic-hypophysial-adrenal axis.

scholarly journals Contribution of the sympathetic hormone epinephrine to the sensitizing effect of ethanol on LPS-induced liver damage in mice

2008 ◽  
Vol 294 (5) ◽  
pp. G1227-G1234 ◽  
Author(s):  
Claudia von Montfort ◽  
Juliane I. Beier ◽  
Luping Guo ◽  
J. Phillip Kaiser ◽  
Gavin E. Arteel
Keyword(s):  
Nervous System ◽  
Liver Disease ◽  
Liver Injury ◽  
Sympathetic Nervous System ◽  
Liver Damage ◽  
Concomitant Administration ◽  
Ethanol Exposure ◽  
Osmotic Pumps ◽  
Sympathetic Nervous ◽  
Sensitizing Effect

It is well known that ethanol preexposure sensitizes the liver to LPS hepatotoxicity. The mechanisms by which ethanol enhances LPS-induced liver injury are not completely elucidated but are known to involve an enhanced inflammatory response. Ethanol exposure also increases the metabolic rate of the liver, and this effect of ethanol on liver is mediated, at least in part, by the sympathetic hormone, epinephrine. However, whether or not the sympathetic nervous system also contributes to the sensitizing effect of ethanol preexposure on LPS-induced liver damage has not been determined. The purpose of this study was therefore to test the hypotheses that 1) epinephrine preexposure enhances LPS-induced liver damage (comparable to that of ethanol preexposure) and that 2) the sympathetic nervous system contributes to the sensitizing effect of ethanol. Accordingly, male C57BL/6J mice were administered epinephrine for 5 days (2 mg/kg per day) via osmotic pumps or bolus ethanol for 3 days (6 g/kg per day) by gavage. Twenty-four hours later, mice were injected with LPS (10 mg/kg ip). Both epinephrine and ethanol preexposure exacerbated LPS-induced liver damage and inflammation. Concomitant administration of propranolol with ethanol significantly attenuated the sensitizing effect of ethanol on LPS-induced liver damage. These data support the hypothesis that the sympathetic nervous system contributes, at least in part, to the mechanism of the sensitizing effect of ethanol. These results also suggest that sympathetic tone may contribute to the initiation and progression of alcoholic liver disease.

Thyroid hormone-catecholamine interrelationships during exposure to cold

1981 ◽  
Vol 97 (1) ◽  
pp. 91-97 ◽  
Author(s):  
H. Storm ◽  
C. van Hardeveld ◽  
A. A. H. Kassenaar
Keyword(s):  
Nervous System ◽  
Plasma Concentration ◽  
Thyroid Hormone ◽  
Sympathetic Nervous System ◽  
Plasma Levels ◽  
Surgical Procedure ◽  
Exposure To Cold ◽  
Basal Plasma ◽  
Sympathetic Nervous

Abstract. Basal plasma levels for adrenalin (A), noradrenalin (NA), l-triiodothyronine (T3), and l-thyroxine (T4) were determined in rats with a chronically inserted catheter. The experiments described in this report were started 3 days after the surgical procedure when T3 and T4 levels had returned to normal. Basal levels for the catecholamines were reached already 4 h after the operation. The T3/T4 ratio in plasma was significantly increased after 3, 7, and 14 days in rats kept at 4°C and the same holds for the iodide in the 24-h urine after 7 and 14 days at 4°C. The venous NA plasma concentration was increased 6- to 12-fold during the same period of exposure to cold, whereas the A concentration remained at the basal level. During infusion of NA at 23°C the T3/T4 ratio in plasma was significantly increased after 7 days compared to pair-fed controls, and the same holds for the iodide excretion in the 24-h urine. This paper presents further evidence for a role of the sympathetic nervous system on T4 metabolism in rats at resting conditions.

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