The vagus nerve in the thermoregulatory response to systemic inflammation

1997 ◽  
Vol 273 (1) ◽  
pp. R407-R413 ◽  
Author(s):  
A. A. Romanovsky ◽  
C. T. Simons ◽  
M. Szekely ◽  
V. A. Kulchitsky
Keyword(s):  
Intravenous Injection ◽  
Systemic Inflammation ◽  
Second Phase ◽  
Thermoregulatory Response ◽  
Cool Environment ◽  
Bolus Intravenous Injection ◽  
High Doses ◽  
Colonic Temperature ◽  
Dose Dependent ◽  
Higher Doses

Experimentally, systemic inflammation induced by a bolus intravenous injection of lipopolysaccharide (LPS) may be accompanied by three different thermoregulatory responses: monophasic fever (the typical response to low doses of LPS), biphasic fever (medium doses), and hypothermia (high doses). In our recent study [Romanovsky, A. A., V. A. Kulchitsky, C. T. Simons, N. Sugimoto, and M. Szekely. Am. J. Physiol. (Regulatory Integrative Comp. Physiol.). In press], monophasic fever did not occur in subdiaphragmatically vagotomized rats. In the present work, we asked whether vagotomy affects the two other types of thermoregulatory response. Adult Wistar rats were vagotomized (or sham operated) and had an intravenous catheter implanted. On day 28 postvagotomy, the thermal responses to the intravenous injection of Escherichia coli LPS (0, 1, 10, 100, or 1,000 micrograms/kg) were tested in either a neutral (30 degrees C) or slightly cool (25 degrees C) environment. Three major results were obtained. 1) In the sham-operated rats, the 1 microgram/kg dose of LPS caused at 30 degrees C a monophasic fever with a maximal colonic temperature (Tc) rise of approximately 0.6 degree C; this response was abated (no Tc changes) in the vagotomized rats. 2) At 30 degrees C, all responses to higher doses of LPS (10-1,000 micrograms/kg) were represented by biphasic fevers (the higher the dose, the less pronounced the first and the more pronounced the second phase was); none of these biphasic fevers was altered in the vagotomized animals. 3) In response to the 1,000 micrograms/kg dose at 25 degrees C, hypothermia occurred: Tc changed by -0.5 +/- 0.1 degree C (nadir); this hypothermia was exaggerated (-1.1 +/- 0.1 degrees C) in the vagotomized rats. It is concluded that vagal afferentation may be important in the mediation of the response to minor amounts of circulating LPS, whereas the response to larger amounts is brought about mostly (if not exclusively) by nonvagal mechanisms. This difference may be explained by the dose-dependent mechanisms of the processing of exogenous pyrogens. Vagotomized animals also appear to be more sensitive to the hypothermizing action of LPS in a cool environment; the mechanisms of this phenomenon remain speculative.

Fever and thermogenesis in response to bacterial endotoxin involve macrophage-dependent mechanisms in rats

1993 ◽  
Vol 265 (5) ◽  
pp. R1179-R1183 ◽  
Author(s):  
R. H. Derijk ◽  
P. J. Strijbos ◽  
N. van Rooijen ◽  
N. J. Rothwell ◽  
F. Berkenbosch
Keyword(s):  
Oxygen Consumption ◽  
Body Temperature ◽  
Intravenous Injection ◽  
Immune Cells ◽  
Interleukin 1 ◽  
Important Mediator ◽  
Selective Elimination ◽  
Colonic Temperature ◽  
Higher Doses ◽  
Intact Rats

Increases in thermogenesis and body temperature (fever) frequently accompany infection or injury and are thought to be mediated by endogenous pyrogens (e.g. cytokines), which are released from activated immune cells such as macrophages. Therefore, we have investigated the effect of selective elimination of peripheral macrophages on the changes in oxygen consumption (VO2) and colonic temperature in response to bacterial lipopolysaccharide (LPS) in the rat. Peripheral macrophages were depleted by intravenous injection of liposomes containing the drug dichloromethylene diphosphonate (Cl2MDP). Resting oxygen consumption and colonic temperatures were not affected by macrophage elimination. In intact rats, peripheral injection of LPS (0.1-0.5 mg/kg) elicited an increase in colonic temperature and in oxygen consumption that declined at higher doses (2.5 mg/kg). The pyrogenic and thermogenic responses to LPS were significantly attenuated in rats in which peripheral macrophages were eliminated. Previously, we have reported that elimination of macrophages blunts the plasma interleukin-1 (IL-1) response to LPS. Here we show that elimination of macrophages does not affect the increase in plasma IL-6 concentrations in response to LPS. These data indicate that the pyrogenic and thermogenic responses to LPS are at least in part dependent on mechanisms involving peripheral macrophages, and that peripherally produced IL-1 rather than IL-6 may be an important mediator of the changes in oxygen consumption and colonic temperature in response to LPS.

scholarly journals Effect of Noni (Morinda citrifoliaLinn.) Fruit and Its Bioactive Principles Scopoletin and Rutin on Rat Vas Deferens Contractility: AnEx VivoStudy

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Vijayapandi Pandy ◽  
Megala Narasingam ◽  
Thubasni Kunasegaran ◽  
Dharmani Devi Murugan ◽  
Zahurin Mohamed
Keyword(s):  
Vas Deferens ◽  
Contractile Response ◽  
Rat Vas Deferens ◽  
Morinda Citrifolia ◽  
Dependent Manner ◽  
Per Se ◽  
High Doses ◽  
Dose Dependent ◽  
Higher Doses ◽  
Agonistic Effect

This study examined the effect of methanolic extract ofMorinda citrifoliaLinn. (MMC) and its bioactive principles, scopoletin and rutin, on dopamine- and noradrenaline-evoked contractility in isolated rat vas deferens preparations. MMC (1–40 mg/mL), scopoletin (1–200 μg/mL), and rutin hydrate (0.6–312.6 μg/mL) dose-dependently inhibited the contractility evoked by submaximal concentrations of both dopamine and noradrenaline, respectively. Haloperidol and prazosin, reference dopamine D2, andα1-adrenoceptors antagonists significantly reversed the dopamine- and noradrenaline-induced contractions, respectively, in a dose-dependent manner. Interestingly, MMCper seat higher doses (60–100 mg/mL) showed dose-dependent contractile response in rat vas deferens which was partially inhibited by high doses of haloperidol but not by prazosin. These results demonstrated the biphasic effects of MMC on dopaminergic system; that is, antidopaminergic effect at lower concentrations (<40 mg/mL) and dopaminergic agonistic effect at higher concentrations (>60 mg/mL). However, similar contractile response at high doses of scopoletin (0.5–5 mg/mL) and rutin hydrate (0.5–5 mg/mL)per sewas not observed. Therefore, it can be concluded that the bioactive principles of MMC, scopoletin, and rutin might be responsible for the antidopaminergic and antiadrenergic activities of MMC.

Effect of Indomethacin and Dazoxiben on Intravascular Platelet Aggregation in the Anaesthetized Rabbit

1986 ◽  
Vol 56 (01) ◽  
pp. 080-085 ◽  
Author(s):  
A C Honey ◽  
N Lad ◽  
D P Tuffin
Keyword(s):  
Platelet Aggregation ◽  
Plasma Levels ◽  
Thromboxane A2 ◽  
Adenosine Diphosphate ◽  
Thromboxane B2 ◽  
Bolus Intravenous Injection ◽  
Cyclic Endoperoxide ◽  
High Doses ◽  
Synthetic Capacity ◽  
Dose Dependent

Summary Collagen (10-40 μg kg−1), thrombin (1-10 units kg−1), adenosine diphosphate (ADP; 3-300 pμ kg−1), 1-0-hexadecyl Paf-acether and 1-0-octadecyl Paf-acether (1-300 ng kg−1) administered by bolus intravenous injection each caused dose-dependent thrombocytopoenia accompanied by marked hypotension in anaesthetized rabbits. Responses to ADP and the Paf-acether derivatives were transient in nature (3-8 min) whereas those induced by collagen and thrombin were always of longer duration (5-20 min) and frequently fatal at high doses. Responses to collagen, thrombin, and the Paf-acether derivatives were invariably accompanied by substantial, dose-related increases in plasma levels of thromboxane B2 in samples obtained 30 s after agonist administration, whereas following ADP, no change in plasma thromboxane B2 was detected at any dose level. Indomethacin (3.0 mg kg−1 by infusion) had no effect on responses to thrombin or Paf-acether, partially inhibited collagen-induced thrombocytopenia, and potentiated responses to ADP. In contrast, dazoxiben (10 mg kg−1 by infusion) partially but significantly inhibited responses to thrombin, whereas those induced by collagen, Paf-acether or ADP were unchanged. These results indicate that in this model of intravascular aggregation, whilst platelet responses to collagen and thrombin appear partially dependent on intact cyclic endoperoxide and thromboxane A2 synthetic capacity respectively, responses to ADP and Paf-acether are independent of arachidonate metabolism via cyclo-oxygenase despite measurably increased TXB2 formation in the latter case.

Dose dependent methotrexate elimination following bolus intravenous injection

1980 ◽  
Vol 17 (5) ◽  
pp. 371-374 ◽  
Author(s):  
J. R. Lawrence ◽  
W. H. Steele ◽  
J. F. B. Stuart ◽  
C. A. McNeill ◽  
J. G. McVie ◽  
...  
Keyword(s):  
Intravenous Injection ◽  
Bolus Intravenous Injection ◽  
Dose Dependent

Inhibition of nitric oxide synthase produces hypothermia and depresses lipopolysaccharide fever

1996 ◽  
Vol 271 (2) ◽  
pp. R333-R338 ◽  
Author(s):  
T. E. Scammell ◽  
J. K. Elmquist ◽  
C. B. Saper
Keyword(s):  
Nitric Oxide ◽  
Low Dose ◽  
Dependent Manner ◽  
Febrile Response ◽  
Bolus Intravenous Injection ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Dose Dependent ◽  
Higher Doses

The labile gas nitric oxide (NO) mediates a wide variety of thermoregulatory processes including vasomotor control, brown fat thermogenesis, and neuroendocrine regulation. Additionally, during endotoxemia, NO modulates the release of cytokines and hypothalamic peptides. To determine the role of NO in thermoregulation and fever, we intravenously injected the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and measured its effects on body temperature during normal thermoregulation and endotoxemia in awake, unrestrained rats. L-NAME produced a stereoselective, dose-dependent hypothermia that lasted up to 4 h after bolus intravenous injection. Intravenous lipopolysaccharide (LPS) produced fever in a dose-dependent manner, which was preceded by hypothermia at higher doses alpha-LPS. NOS inhibition reduced the febrile response to LPS and produced marked hypothermia with a low dose of LPS. These findings indicate that NO may play an important role in thermoregulation and suggest that NO is required for the production of fever.

Thermoregulatory responses to lipopolysaccharide in the mouse: dependence on the dose and ambient temperature

2005 ◽  
Vol 289 (5) ◽  
pp. R1244-R1252 ◽  
Author(s):  
Alla Y. Rudaya ◽  
Alexandre A. Steiner ◽  
Jared R. Robbins ◽  
Alexander S. Dragic ◽  
Andrej A. Romanovsky
Keyword(s):  
Ambient Temperature ◽  
Dose Range ◽  
Dose Dependence ◽  
Experimental Conditions ◽  
Thermoregulatory Responses ◽  
Hypothermic Response ◽  
High Doses ◽  
The Relationship ◽  
Dose Dependent ◽  
Higher Doses

Most published studies of thermoregulatory responses of mice to LPS involved a stressful injection of LPS, were run at a poorly controlled and often subneutral ambient temperature (Ta), and paid little attention to the dependence of the response on the LPS dose. These pitfalls have been overcome in the present study. Male C57BL/6 mice implanted with jugular vein catheters were kept in an environmental chamber at a tightly controlled Ta. The relationship between the Tas used and the thermoneutral zone of the mice was verified by measuring tail skin temperature, either by infrared thermography or thermocouple thermometry. Escherichia coli LPS in a wide dose range (100-104μg/kg) was administered through an extension of the jugular catheter from outside the chamber. The responses observed were dose dependent. At a neutral Ta, low (just suprathreshold) doses of LPS (100-101μg/kg) caused a monophasic fever. To a slightly higher dose (101.5μg/kg), the mice responded with a biphasic fever. To even higher doses (101.75-104μg/kg), they responded with a polyphasic fever, of which three distinct phases were identified. The dose dependence and dynamics of LPS fever in the mouse appeared to be remarkably similar to those seen in the rat. However, the thermoregulatory response of mice to LPS in a subthermoneutral environment is remarkably different from that of rats. Although very high doses of LPS (104μg/kg) did cause a late (latency, ∼3 h) hypothermic response in mice, the typical early (latency, 10–30 min) hypothermic response seen in rats did not occur. The present investigation identifies experimental conditions to study LPS-induced mono-, bi-, and polyphasic fevers and late hypothermia in mice and provides detailed characteristics of these responses.

Mechanism of Action of Trazodone: a Multifunctional Drug

CNS Spectrums ◽  
2009 ◽  
Vol 14 (10) ◽  
pp. 536-546 ◽  
Author(s):  
Stephen M. Stahl
Keyword(s):  
Controlled Release ◽  
Adrenergic Receptors ◽  
Low Dose ◽  
Low Doses ◽  
Release Formulation ◽  
Therapeutic Mechanism ◽  
High Doses ◽  
Pharmacologic Actions ◽  
Dose Dependent ◽  
Higher Doses

Multifunctional drugs are those with more than one therapeutic mechanism. Trazodone is a multifunctional drug with dose-dependent pharmacologic actions. That is, it has hypnotic actions at low doses due to blockade of 5-HT2A receptors, as well as H1 histamine receptors and α1 adrenergic receptors. Higher doses recruit the blockade of the serotonin transporter (SERT) and turn trazodone into an antidepressant. Although trazodone has traditionally been used as a low dose hypnotic, a new controlled release formulation that has the potential to improve the tolerability of high doses may provide an opportunity to revisit this multifunctional drug as an antidepressant as well.

Interleukin-6 is a centrally acting endogenous pyrogen in the rat

1991 ◽  
Vol 69 (10) ◽  
pp. 1465-1469 ◽  
Author(s):  
N. J. Rothwell ◽  
N. J. Busbridge ◽  
R. A. Lefeuvre ◽  
A. J. Hardwick ◽  
J. Gauldie ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Cyclooxygenase Inhibitor ◽  
Endogenous Pyrogen ◽  
Conscious Rats ◽  
Corticotrophin Releasing Factor ◽  
High Doses ◽  
Colonic Temperature ◽  
Higher Doses ◽  
Very High ◽  
Factor Antagonist

Intracerebroventricular (i.c.v.) injection of human recombinant interleukin-6 (IL-6; 20–100 ng) caused significant increases in colonic temperature and resting oxygen consumption [Formula: see text] in conscious rats. These effects were prevented by pretreatment with a cyclooxygenase inhibitor (flurbiprofen, 1 mg/kg, i.p.) or a corticotrophin-releasing factor antagonist (α-helical CRF 9–41, 25 μg, i.c.v.). Higher doses of IL-6 (i.c.v.) caused only small changes in [Formula: see text] and temperature, and very high doses given intravenously (i.v.) (4 μg/kg) were required to stimulate these parameters. Central injection of anti-rat IL-6 antibody inhibited the effects of interleukin-1β (i.c.v.) or endotoxin injection (i.p.) on colonic temperature and [Formula: see text] in conscious rats. These data indicate that IL-6 is an important endogenous pyrogen that acts within the central nervous system.Key words: interleukin 6, fever, thermogenesis, brain, pyrogen.

Biphasic Prolonged Inhibition of Platelet Prostaglandin Biosynthesis Induced by Sulphinpyrazone

1979 ◽  
Author(s):  
K.D. Butler ◽  
G.F. Pay ◽  
R.B. Wallis ◽  
A.M. White
Keyword(s):  
Platelet Aggregation ◽  
Oral Administration ◽  
Plasma Proteins ◽  
Peak Plasma ◽  
Second Phase ◽  
Arthus Reaction ◽  
Prostaglandin Biosynthesis ◽  
High Doses ◽  
Higher Doses

In rabbits, high doses of sulphinpyrazone (S) result in prolonged inhibition of in vivo collagen-induced thrombocytopenia and platelet MDA production (Buchanan et al., Thromb. Res. 1978, 13, 883). After confirming these results we have shown in guinea pigs that 7 h after oral administration of S there was greater inhibition of AA-induced platelet aggregation than 1 h afterwards, i.e. at the peak plasma S concentration. Thus the concentration of AA needed to induce 50% maximal platelet aggregation at 7 h was raised 2.36 times and 4.73 times after 3 mg/kg and 10 mg/kg of S respectively. When in vivo thrombocytopenia was induced with the Arthus reaction the second phase of inhibition occurred down to a dose of 10 mg/kg p.o. with the first phase seen at higher doses. The inhibitory activity is associated with a high M.W. fraction of plasma proteins [50,000-100,000 Daltons). Phenylbutazone, aspirin and ticlopidine did not induce the plasma-borne effect.

Biphasic Prolonged Inhibition of Platelet Prostaglandin Biosynthesis Induced by Sulphinpyrazone

1979 ◽  
Author(s):  
K Butler ◽  
G Pay ◽  
R Wallis ◽  
A White
Keyword(s):  
Platelet Aggregation ◽  
Oral Administration ◽  
Plasma Proteins ◽  
Peak Plasma ◽  
Second Phase ◽  
Arthus Reaction ◽  
Prostaglandin Biosynthesis ◽  
High Doses ◽  
Higher Doses

In rabbits, high doses of sulphinpyrazone (S) result in prolonged inhibition of in vivo collagen-induced thrombocytopenia and platelet MDA production (Buchanan et al., Thromb. Res. 1978, 13., 883). After confirming these results we have shown in guinea pigs that 7 h after oral administration of S there was greater inhibition of AA-induced platelet aggregation than 1 h afterwards, i.e. at the peak plasma S concentration. Thus the concentration of AA needed to induce 50% maximal platelet aggregation at 7 h was raised 2.36 times and 4.73 times after 3 mg/kg and 10 mg/kg of S respectively. When in vivo thrombocytopenia was induced with the Arthus reaction the second phase of inhibition occurred down to a dose of 10 mg/kg p.o. with the first phase seen at higher doses. The inhibitory activity is associated with a high M.W. fraction of plasma proteins (50,000-100,000 Daltons). Phenylbutazone, aspirin andticlopidine did not induce the plasma-borne effect.

Sign in / Sign up

Export Citation Format

Share Document