Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that the nitric oxide (NO) pathway in the central nervous system (CNS) plays a role in hypothermia, as well as in the febrile response during experimental septic shock, by regulating vasopressin (AVP) release. Experiments were performed on male Wistar rats treated with NG-nitro-L-arginine methyl ester (L-NAME), a non-selective NO synthase (NOS) inhibitor, injected intracerebroventricularly (250 microg/1 microl) 30 min before lipopolysaccharide (LPS) 1.5 mg/kg i.v. injection. One hour after LPS administration we observed a significant drop in body temperature (hypothermic response), followed by a temperature increase after the second hour (febrile response), which remained until the end of the experiment. Increased plasmatic AVP levels were concomitantly observed during hypothermia, nearly returning to basal levels during the febrile phase. When L-NAME was administered with LPS, plasmatic AVP concentrations remained high throughout the experiment, hypothermia was accentuated and the febrile response was abolished. Additionally, pre-treatment with beta-mercapto-beta,beta-cyclopentamethylenepropionyl1, O-Et-Tyr2, Val4, Arg8-vasopressin, an AVP V1 receptor blocker (10 microg/kg) administered i.v., reduced hypothermia and exacerbated the febrile response to endotoxin. In conclusion, our data indicate that the central NO pathway plays an inhibitory role in AVP release during experimental septic shock, which seems to be critical for the thermoregulation during this pathophysiological state.
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PMID:Role of nitric oxide in thermoregulation during septic shock: involvement of vasopressin. 1453 Sep 75

Secretion and synthesis of vasopressin was studied in adult male Wistar rats receiving lipopolysaccharide in a dose of 250 microg/100 g body weight and subjected to moderate osmotic stimulation (2% NaCl perorally for 6 days). Lipopolysaccharide stimulated secretion of vasopressin into the blood. It should be emphasized that the content of vasopressin mRNA in gigantocellular nuclei of the hypothalamus decreased, which probably reflected intensification of its translation. The observed changes and slight increase in transcription of the vasopressin gene (determined by the content of heterogeneous nuclear RNA) provide intensive secretion of this neurohormone into the blood.
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PMID:Effect of bacterial endotoxin on secretion and synthesis of vasopressin during saline load in rats. 1463 90

1. Our study was undertaken to investigate whether bacterial endotoxin/lipopolysaccharide (LPS) affects the neurogenic vasopressor response in rats in vivo by presynaptic mechanisms and, if so, to characterize the type of presynaptic receptor(s) operating in the initial phase of septic shock. 2. In pithed and vagotomized rats treated with pancuronium, electrical stimulation (ES) (1 Hz, 1 ms, 50 V for 10 s) of the preganglionic sympathetic nerve fibers or intravenous bolus injection of noradrenaline (NA) (1-3 nmol x kg(-1)) increased the diastolic blood pressure (DBP) by about 30 mmHg. Administration of LPS (0.4 and 4 mg x kg(-1)) under continuous infusion of vasopressin inhibited the neurogenic vasopressor response by 25 and 50%, respectively. LPS did not affect the increase in DBP induced by exogenous NA. 3. The LPS-induced inhibition of the neurogenic vasopressor response was counteracted by the cannabinoid CB(1) receptor antagonist SR 141716A (0.1 micromol x kg(-1)), but not by the CB(2) receptor antagonist SR 144528 (3 micromol x kg(-1)), the vanilloid VR1 receptor antagonist capsazepine (1 micromol x kg(-1)) or the histamine H(3) receptor antagonist clobenpropit (0.1 micromol x kg(-1)). The four antagonists by themselves did not affect the increase in DBP induced by ES or by injection of NA in rats not exposed to LPS. 4. We conclude that in the initial phase of septic shock, the activation of presynaptic CB(1) receptors by endogenously formed cannabinoids contributes to the inhibition of the neurogenic vasopressor response.
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PMID:Presynaptic cannabinoid CB(1) receptors are involved in the inhibition of the neurogenic vasopressor response during septic shock in pithed rats. 1515 84

The serotonin-3 (5-HT-3A) receptor has been localized in limbic and brainstem structures that regulate anxiety-related behavior and hypothalamic-pituitary-adrenal (HPA) activity, but its role in regulating anxiety-related behaviors is equivocal, and evidence for its role in regulating HPA activity is limited. Therefore, we used 5-HT-3A receptor knockout (KO) mice to further study these issues. Behavior in the elevated plus maze, open field, light-dark box and after Pavlovian fear conditioning was examined in addition to HPA activity under basal and acute stress conditions. Compared to age-matched adult male wild-type (WT) controls, adult male KO mice exhibited increased distance traveled in the open arms of the elevated plus maze, consistent with decreased measures of anxiety. There were no differences between the two genotypes in exploratory behavior in the open field or light-dark test. KO mice displayed enhanced fear conditioning indexed by fear-induced freezing behavior. KO mice displayed lower adrenocorticotropin (ACTH) responses to restraint or lipopolysaccharide (LPS). In addition, lower vasopressin mRNA in the paraventricular nucleus of the hypothalamus (PVN) and higher corticotropin-releasing hormone (CRH) mRNA in the central amygdala were observed in KO compared to WT mice. Therefore, deletion of the 5-HT-3A receptor revealed an important role for this receptor in regulating HPA responses to acute stress and a potential interaction between the 5-HT-3A receptor and CRH in the amygdala. Together, these data suggest that the 5-HT-3A receptor does not have a unitary role in the regulation of anxiety- and fear-related behaviors but has a potentially substantial role in the regulation of HPA activity.
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PMID:Changes in anxiety-related behaviors and hypothalamic-pituitary-adrenal activity in mice lacking the 5-HT-3A receptor. 1517 47

Gamma-aminobutyric acid (GABA) receptor plays an important regulatory role in human and animal blood pressure; however, whether a GABAergic mechanism is involved in endotoxin intoxication-associated hypotension has never been reported. In vivo effect of the GABA(A) receptor antagonist bicuculline methiodide (BMI) on mean arterial pressure (MAP), heart rate (HR), and serum nitrite levels were investigated in endotoxin (lipopolysaccharide; LPS)-treated rats. BMI increased MAP and decreased HR in LPS-stimulated rats. DOAV ([deamino-Pen, O-Me-Tyr, Arg3]-vasopressin), an arginine vasopressin (AVP) antagonist, reversed the hemodynamic improvement resulted from BMI in LPS-intoxicated rats. Based on a two-factor (BMI treatment by LPS dose) factorial design, BMI reduced the serum nitrite production induced by LPS. DOAV plus BMI, however, did not affect the serum nitrite level in LPS-intoxicated rats. Thus, GABA receptor antagonist BMI might attenuate hypotension in endotoxin intoxication in rats.
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PMID:Effect of GABA(A) receptor antagonist bicuculline methiodide on hypotension in endotoxin-intoxicated rats. 1521 17

Expression of antidiuretic hormone V(2)-receptor, water channel protein aquaporin-2, and cytokines interleukin-1b and interleukin-6 was studied in the kidneys of rats with acute inflammation produced by intraperitoneal injection of lipopolysaccharide in a dose of 250 microg/100 g. Reduced expression of aquaporin-2 and V(2)-receptor led to impairment of concentration capacity in the kidneys and decrease in urine osmolarity.
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PMID:Antidiuretic hormone-V2-receptor-aquaporin-2 system in rat kidneys during acute inflammation. 1572 24

Nitric oxide (NO) and carbon monoxide (CO) are endogenously synthesized gaseous molecules that act as neurotransmitters in central nervous system. In this study we investigated the modulatory role of NO and CO in lipopolysaccharide (LPS)-induced vasopressin and oxytocin secretion. Intracerebroventricular (i.c.v.) injection of N omega-L-nitro-arginine methyl ester (L-NAME), 3-morpholino-sydnonimine (SIN-1), zinc deuteroporphyrin 2,4-bis glicol (ZnDPBG) or hemin did not change the basal vasopressin and oxytocin plasma levels. After endovenous LPS administration, plasma vasopressin and oxytocin increased, reaching a peak at 60 min, and returning to basal levels afterwards. LPS administration induced a higher vasopressin and oxytocin plasma levels in rats previously treated with L-NAME and ZnDPBG (P<0.05) compared to rats pre-treated with vehicle. On the other hand, in rats previously treated with SIN-1 or hemin, there was a significant reduction in the vasopressin and oxytocin secretion. These findings confirm the inhibitory role of NO and CO in the LPS-induced vasopressin and oxytocin secretion.
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PMID:Inhibitory effect of gaseous neuromodulators in vasopressin and oxytocin release induced by endotoxin in rats. 1589 92

We tested the hypothesis that nitric oxide (NO) arising from the action of inducible nitric oxide synthase (iNOS) is responsible for the deficiency in vasopressin (AVP) release and consequent hypotension during endotoxaemic shock. Wild-type (WT) and iNOS knockout mice (iNOS(-/-)) were given either saline or Escherichia coli lipopolysaccharide (LPS, 1.0 mg/kg i.v., final volume 0.03 ml). Mean arterial blood pressure (MAP) was measured and plasma AVP levels determined before and after LPS or saline injection. In WT mice, MAP was significantly lower 2 h after LPS administration and remained low for the remainder of the 6-h observation period. AVP plasma levels were increased at the 2nd and 4th h of the experiment, returning thereafter to basal levels. Conversely, LPS injection in iNOS iNOS(-/-) mice elicited a sustained increase in plasma AVP concentration and attenuated the fall in blood pressure. These data indicate that NO arising from the iNOS plays an important inhibitory role in AVP release during endotoxaemia and may be responsible for the hypotension occurring during this vasodilatory shock.
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PMID:Vasopressin release during endotoxaemic shock in mice lacking inducible nitric oxide synthase. 1597 Oct 84

Nitric oxide (NO) is produced in almost all tissues and organs, exerting a variety of biological actions under physiological and pathological conditions. NO is synthesized by three different isoforms of NO synthase (NOS), including neuronal, inducible, and endothelial NOSs. Because there are substantial compensatory interactions among the NOS isoforms, the ultimate roles of endogenous NO in our body still remain to be fully elucidated. Here, we have successfully developed mice in which all three NOS genes are completely deleted by crossbreeding singly NOS-/- mice. NOS expression and activities were totally absent in the triply NOS-/- mice before and after treatment with lipopolysaccharide. Although the triply NOS-/- mice were viable and appeared normal, their survival and fertility rates were markedly reduced as compared with the wild-type mice. Furthermore, these mice exhibited marked hypotonic polyuria, polydipsia, and renal unresponsiveness to an antidiuretic hormone, vasopressin, all of which are characteristics consistent with nephrogenic diabetes insipidus. In the kidney of the triply NOS-/- mice, vasopressin-induced cAMP production and membranous aquaporin-2 water channel expression were reduced associated with tubuloglomerular lesion formation. These results provide evidence that the NOS system plays a critical role in maintaining homeostasis, especially in the kidney.
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PMID:Nephrogenic diabetes insipidus in mice lacking all nitric oxide synthase isoforms. 1602 29

We have tested the hypothesis that nitric oxide (NO) arising from inducible nitric oxide synthase (iNOS) plays a role in hypothermia during endotoxemia by regulating vasopressin (AVP) release. Wild-type (WT) and iNOS knockout mice (KO) were intraperitoneally injected with either saline or Escherichia coli lipopolysaccharide (LPS) 10.0 mg/kg in a final volume of 0.02 mL. Body temperature was measured continuously by biotelemetry during 24 h after injection. Three hours after LPS administration, we observed a significant drop in body temperature (hypothermic response) in WT mice, which remained until the seventh hour, returning then close to the basal level. In iNOS KO mice, we found a significant fall in body temperature after the fourth hour of LPS administration; however, the hypothermic response persisted until the end of the 24 h of the experiment. The pre-treatment with beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1), O-Et-Tyr2, Val4, Arg8-Vasopressin, an AVP V1 receptor antagonist (10 microg/kg) administered intraperitoneally, abolished the persistent hypothermia induced by LPS in iNOS KO mice, suggesting the regulation of iNOS under the vasopressin release in this experimental model. In conclusion, our data suggest that the iNOS isoform plays a role in LPS-induced hypothermia, apparently through the regulation of AVP release.
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PMID:Thermoregulatory role of inducible nitric oxide synthase in lipopolysaccharide-induced hypothermia. 1671 35


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