Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0020672 (hypothermia)
17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that nitric oxide (NO) is involved in the development of rapid tolerance to the motor incoordination produced by ethanol. In order to further investigate this involvement, three experiments were undertaken using the tilt-plane and the hypothermia tests. The first demonstrated that 7-nitroindazole (7-NI), a preferential neuronal NO synthase (nNOS) inhibitor, injected by intracerebroventricular (i.c.v.) route, blocked the development of rapid tolerance to ethanol-induced motor incoordination. This effect was prevented by i.c.v. injection of L-arginine. The second experiment showed that D-arginine did not influence the blockade of tolerance produced by 7-NI. The third experiment revealed that i.c.v. injection of 7-NI also blocked the development of tolerance to the hypothermic effect of ethanol. These results support the hypothesis that nNOS-derived NO participates in the development of rapid tolerance to ethanol.
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PMID:Effects of intracerebroventricular administration of 7-nitroindazole on tolerance to ethanol. 1184 22

Hepatic ischemia-reperfusion injury is an important cause of graft dysfunction after liver transplantation. Liver sinusoidal endothelial cells (LSECs) are particularly sensitive to ischemia-reperfusion injury and undergo apoptosis. This study investigates the protective role of PGE(1) on apoptosis of LSEC during hypoxia-reoxygenation in vitro. Hypothermia-hypoxia followed by reoxygenation triggered LSEC apoptosis, and prostaglandin PGE(1) protected LSEC from apoptosis in a dose-dependent manner. The release of matrix metalloproteinases (MMPs) and nitric oxide (NO) by LSECs were increased after hypoxia reoxygenation. Both the MMP inhibitor BB3103 and the NO inhibitor LNAM effectively decreased LSEC apoptosis, suggesting a separate role of MMPs and NO in hypoxia-reoxygenation-induced LSEC apoptosis. PGE(1) down-regulated NO production by inhibiting the expression of inducible NO synthase in LSEC. PGE(1) also inhibited MMP-2 release from LSEC during hypoxia reoxygenation. These results indicate that the protection of LSECs from apoptosis by PGE(1) in hepatic ischemia-reperfusion injury is mediated by inhibiting inducible NO synthase and MMP release.
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PMID:Prostaglandin E(1) protects human liver sinusoidal endothelial cell from apoptosis induced by hypoxia reoxygenation. 1207 35

Nitric oxide (NO) is postulated to play a role in endotoxin-induced ileus. We investigated the effect of selective blockade of inducible NO synthase (iNOS) and guanylyl cyclase on endotoxin-induced ileus in mice. Thirty minutes before injection of lipopolysaccharides (LPS), mice were pretreated with L-NAME (N omega-nitro-L-arginine methyl ester, non-selective NOS inhibitor), 1400W (N-(3-(aminomethyl)benzyl)acetamide, selective iNOS inhibitor), ODQ (1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one, guanylyl cyclase inhibitor), dimethyl sulfoxide (DMSO, vehicle), or dexamethasone. After 18 h, general well being deteriorated and the mice developed hypothermia and a significant delay in gastric emptying and intestinal transit as measured by Evans blue. 1400W completely reversed the endotoxin-induced delay in gastric emptying, while L-NAME did not have these beneficial effects. On the contrary, even in control mice, L-NAME delayed gastric emptying. Dexamethasone, DMSO, and ODQ mimicked the effect of 1400W on endotoxin-induced delay in gastric emptying. The endotoxin-induced delay in transit was significantly improved only by 1400W. None of the drugs reversed the hypothermia. In LPS mice treated with L-NAME, the behavior scale increased even further, while it decreased after treatment with 1400W. In conclusion, selective inhibition of iNOS reverses the endotoxin-induced delay in gastric emptying and transit and improves general well being. The pathway used by NO, derived from iNOS, may involve inhibition of guanylyl cyclase or radical scavenging.
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PMID:Effect of inhibition of inducible nitric oxide synthase and guanylyl cyclase on endotoxin-induced delay in gastric emptying and intestinal transit in mice. 1216 74

Porcine cerebral arterial strips denuded of the endothelium responded to transmural electrical stimulation (5 Hz for 40 s) with a relaxation, which was abolished by tetrodotoxin and N (G)-nitro-L-arginine, a NO synthase inhibitor. Lowering the temperature of the bathing media from 37 degrees C to 33 degrees C or 25 degrees C potentiated the response to nerve stimulation, but did not affect relaxations induced by NO applied exogenously. Hypoxia suppressed the stimulation-induced relaxation at 37 degrees C, but hypothermia blunted the inhibitory effect of hypoxia in a temperature-dependent manner. It is concluded that hypothermia augments vasodilatation associated with nitroxidergic (nitrergic) nerve activation possibly by increasing the production of NO from L-arginine and, in addition, prevents impairment of NO production by hypoxia. These mechanisms likely explain how hypothermia protects nerve cells against hypoxia. Inhibitions of cyclic GMP phosphodiesterase and of superoxide production by hypoxia do not seem to participate in the action of hypothermia. Mechanisms underlying its protective action remain to be ascertained.
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PMID:Protection by hypothermia of hypoxia-induced inhibition of neurogenic vasodilation in porcine cerebral arteries. 1283 36

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

Cannabinoids evoke profound hypothermia in rats by activating central CB(1) receptors. Nitric oxide (NO), a prominent second messenger in central and peripheral neurons, also plays a crucial role in thermoregulation, with previous studies suggesting pyretic and antipyretic functions. Dense nitric-oxide synthase (NOS) staining and CB(1) receptor immunoreactivity have been detected in regions of the hypothalamus that regulate body temperature, suggesting that intimate NO-cannabinoid associations may exist in the central nervous system. The present study investigated the effect of N(omega)-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, on the hypothermic response to WIN 55212-2 [4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenylcarbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one], a selective cannabinoid agonist, in rats. WIN 55212-2 (1-5 mg/kg, i.m.) produced dose-dependent hypothermia that peaked 45 to 90 min post-injection. L-NAME (10-100 mg/kg, i.m.) by itself did not significantly alter body temperature. However, a nonhypothermic dose of L-NAME (50 mg/kg) potentiated the hypothermia caused by WIN 55212-2 (0.5-5 mg/kg). The augmentation was strongly synergistic, indicated by a 2.5-fold increase in the relative potency of WIN 55212-2. The inactive enantiomer of WIN 55212-2, WIN 55212-3 [S-(-)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-napthanlenyl) methanone mesylate] (5 mg/kg, i.m.), did not produce hypothermia in the absence or presence of L-NAME (50 mg/kg), confirming that cannabinoid receptors mediated the synergy. The present data are the first evidence that drug combinations of NOS blockers and cannabinoid agonists produce synergistic hypothermia. Thus, NO and cannabinoid systems may interact to induce superadditive hypothermia.
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PMID:L-NAME (N omega-nitro-L-arginine methyl ester), a nitric-oxide synthase inhibitor, and WIN 55212-2 [4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one], a cannabinoid agonist, interact to evoke synergistic hypothermia. 1461 Feb 31

The purpose of this study was to investigate changes in nitric oxide (NO) synthesis induced by exogenous glutamate perfusion into the cerebral cortex, and the effects of mild hypothermia on this glutamate-induced NO synthesis. Glutamate-induced cortical lesions were produced by perfusion of 0.5 M glutamate solution via a microdialysis probe, and the extracellular concentrations of NO end-products (nitrite and nitrate) were measured by microdialysis in normothermic (37 degrees C) and hypothermic (32 degrees C) rats. The levels of NO end-products in the normothermia group were elevated markedly by glutamate perfusion, and this change was completely attenuated by the induction of hypothermia. The glutamate-induced increases were also attenuated markedly by both Nomega-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI). These results suggest that the perfusion of exogenous glutamate into the cortex induces NO synthesis, that is derived primarily from the activity of neuronal NO synthase. These results also demonstrate that hypothermia prevents this glutamate-induced increase in NO, suggesting that the protection afforded by the hypothermic condition is most likely linked to its inhibition of the glutamate-induced NO synthesis.
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PMID:Mild hypothermia inhibits exogenous glutamate-induced increases in nitric oxide synthesis. 1465 5

Optimal timing of therapeutic hypothermia for cardiac ischemia is unknown. Our prior work suggests that ischemia with rapid reperfusion (I/R) in cardiomyocytes can be more damaging than prolonged ischemia alone. Also, these cardiomyocytes demonstrate protein kinase C (PKC) activation and nitric oxide (NO) signaling that confer protection against I/R injury. Thus we hypothesized that hypothermia will protect most using extended ischemia and early reperfusion cooling and is mediated via PKC and NO synthase (NOS). Chick cardiomyocytes were exposed to an established model of 1-h ischemia/3-h reperfusion, and the same field of initially contracting cells was monitored for viability and NO generation. Normothermic I/R resulted in 49.7 +/- 3.4% cell death. Hypothermia induction to 25 degrees C was most protective (14.3 +/- 0.6% death, P < 0.001 vs. I/R control) when instituted during extended ischemia and early reperfusion, compared with induction after reperfusion (22.4 +/- 2.9% death). Protection was completely lost if onset of cooling was delayed by 15 min of reperfusion (45.0 +/- 8.2% death). Extended ischemia/early reperfusion cooling was associated with increased and sustained NO generation at reperfusion and decreased caspase-3 activation. The NOS inhibitor N(omega)-nitro-L-arginine methyl ester (200 microM) reversed these changes and abrogated hypothermia protection. In addition, the PKCepsilon inhibitor myr-PKCepsilon v1-2 (5 microM) also reversed NO production and hypothermia protection. In conclusion, therapeutic hypothermia initiated during extended ischemia/early reperfusion optimally protects cardiomyocytes from I/R injury. Such protection appears to be mediated by increased NO generation via activation of protein kinase Cepsilon; nitric oxide synthase.
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PMID:Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling. 1717 66

The present study was undertaken to evaluate: (1) whether lipopolysaccharide LPS-induced hypothermic responses may be altered during two estrous cycle phases, proestrus and diestrus, and after ovariectomy, followed by hormonal supplementation and (2) whether nitric oxide (NO) plays a role on LPS-induced hypothermia responses in female mice. Experiments were performed on adult female wild-type (WT) C57BL and inducible NO synthase knockout (KO) mice weighing 18 to 30 g. Endotoxemia was induced by intraperitoneal LPS administration from Escherichia coli at a nonlethal dose of 10 mg/kg, and body temperature was measured by biotelemetry. Hormonal replacement was performed in ovariectomized mice through 17beta-estradiol Silastic capsules (100 mug) and s.c. injection of progesterone (0.5 mg per animal). We observed that during the diestrus phase, mice presented more intensive hypothermia than during proestrus phase, and hormonal supplementation with 17beta-estradiol and progesterone attenuated hypothermia in ovariectomized mice. During diestrus and ovariectomy, KO mice had higher hypothermic response when compared with the WT group. During proestrus, the lack of statistical difference between KO and WT mice could be consequent of lower ovarian hormones plasma levels. After hormonal replacement, hypothermia was reverted in KO groups probably because of higher ovarian hormonal levels. In summary, the results demonstrated that NO release by inducible NO synthase has an important thermoregulatory role in LPS-induced hypothermia in female mice. Besides, this involvement is directly dependent on the presence of ovarian hormones and their respective levels.
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PMID:Hypothermia during endotoxemic shock in female mice lacking inducible nitric oxide synthase. 1762 Dec 53

Perinatal asphyxia (PA) is able to induce sequelae such as spinal spasticity. Previously, we demonstrated hypothermia as a neuroprotective treatment against cell degeneration triggered by increased nitric oxide (NO) release. Because spinal motoneurons are implicated in spasticity, our aim was to analyze the involvement of NO system at cervical and lumbar motoneurons after PA as well as the application of hypothermia as treatment. PA was performed by immersion of both uterine horns containing full-term fetuses in a water bath at 37 degrees C for 19 or 20 min (PA19 or PA20) or at 15 degrees C for 20 min (hypothermia during PA-HYP). Some randomly chosen PA20 rats were immediately exposed for 5 min over grain ice (hypothermia after PA-HPA). Full-term vaginally delivered rats were used as control (CTL). We analyzed NO synthase (NOS) activity, expression and localization by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) reactivity, inducible and neuronal NOS (iNOS and nNOS) by immunohistochemistry, and protein nitrotyrosilation state. We observed an increased NOS activity at cervical spinal cord of 60-day-old PA20 rats, with increased NADPH-d, iNOS, and nitrotyrosine expression in cervical motoneurons and increased NADPH-d in neurons of layer X. Lumbar neurons were not altered. Hypothermia was able to maintain CTL values. Also, we observed decreased forelimb motor potency in the PA20 group, which could be attributed to changes at cervical motoneurons. This study shows that PA can induce spasticity produced by alterations in the NO system of the cervical spinal cord. Moreover, this situation can be prevented by perinatal hypothermia.
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PMID:Nitric oxide system alteration at spinal cord as a result of perinatal asphyxia is involved in behavioral disabilities: hypothermia as preventive treatment. 1900 88


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