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)

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

In the present study, the interaction of nitric oxide synthase (NOS) inhibitors, L-NAME (N(G)-nitro-L-arginine methyl ester HCl) and L-NA (N(omega)-nitro-L-arginine), and its precursor, L-arginine (2-(S)-2-amino-5-[(aminoiminomethyl)amino] pentatonic acid), with theophylline on mouse body temperature was studied. Intraperitoneal (i.p.) injection of different doses of theophylline altered body temperature. Lower doses of theophylline (12.5 and 25 mg/kg) increased, but a higher dose (100 mg/kg) reduced, the animals' body temperature. The combination of L-arginine (20 and 40 mg/kg) with the highest dose of theophylline potentiated the hypothermic effect induced by the latter drug, while L-arginine by itself did not alter body temperature. L-NAME (10-80 mg/kg) or L-NA (10 mg/kg) plus a lower dose of theophylline (12.5 mg/kg) reduced the theophylline-induced hyperthermic response. L-NA (1, 5, and 10 mg/kg) in combination with the high dose of theophylline (100 mg/kg) also induced greater hypothermia. Both L-NAME and L-NA by themselves reduced body temperature. It is concluded that nitric oxide (NO) may be involved in the effects of theophylline on body temperature in mice.
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PMID:Role of nitric oxide in systemic effect of theophylline on mouse body temperature. 1222 30

The effect of central and peripheral administration of a nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on the hypothermia induced by the selective kappa-opioid receptor agonist trans-(+/-)3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)-benzeneacetamide methane sulfate (U50,488H) was studied in male Sprague-Dawley rats. In the first series of experiments, we examined the effect of subcutaneous (s.c.) administration of L-NAME on the hypothermia induced by s.c. injection of U50,488H. L-NAME, at a dose of 50 mg/kg s.c., had no influence on body temperature (Tb). Coadministration of L-NAME (50 mg/kg, s.c.) with U50,488H (10 mg/kg, s.c.) blocked the hypothermia induced by U50,488H. In the second series of experiments, we investigated the effect of intracerebroventricular (i.c.v.) administration of L-NAME on the hypothermia induced by s.c. injection of U50,488H. L-NAME itself, given i.c.v. at a dose of 1 mg/rat, did not evoke any change in Tb. Administration of L-NAME (1 mg/rat, i.c.v.) caused a significant suppression of U50,488H hypothermia. The results indicate that either central or peripheral nitric oxide synthesis is required for the production of hypothermia induced by U50,488H.
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PMID:Role of the nitric oxide pathway in kappa-opioid-induced hypothermia in rats. 1223 73

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

Hypothermic perfusion of the heart decreases oxidative phosphorylation and increases NADH. Because O(2) and substrates remain available and respiration (electron transport system, ETS) may become impaired, we examined whether reactive oxygen species (ROS) exist in excess during hypothermic perfusion. A fiberoptic probe was placed on the left ventricular free wall of isolated guinea pig hearts to record intracellular ROS, principally superoxide (O(2)(-).), and an extracellular reactive nitrogen reactant, principally peroxynitrite (ONOO(-)), a product of nitric oxide (NO.) + O(2)(-). Hearts were loaded with dihydroethidium (DHE), which is oxidized by O(2)(-). to ethidium, or were perfused with l-tyrosine, which is oxidized by ONOO(-) to dityrosine (diTyr). Shifts in fluorescence were measured online; diTyr fluorescence was also measured in the coronary effluent. To validate our methods and to examine the source and identity of ROS during cold perfusion, we examined the effects of a superoxide dismutase mimetic Mn(III) tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME), and several agents that impair electron flux through the ETS: menadione, sodium azide (NaN(3)), and 2,3-butanedione monoxime (BDM). Drugs were given before or during cold perfusion. ROS measured by DHE was inversely proportional to the temperature between 37 degrees C and 3 degrees C. We found that perfusion at 17 degrees C increased DHE threefold versus perfusion at 37 degrees C; this was reversed by MnTBAP, but not by l-NAME or BDM, and was markedly augmented by menadione and NaN(3). Perfusion at 17 degrees C also increased myocardial and effluent diTyr (ONOO(-)) by twofold. l-NAME, MnTBAP, or BDM perfused at 37 degrees C before cooling or during 17 degrees C perfusion abrogated, whereas menadione and NaN(3) again enhanced the cold-induced increase in ROS. Our results suggest that hypothermia moderately enhances O(2)(-). generation by mitochondria, whereas O(2)(-). dismutation is markedly slowed. Also, the increase in O(2)(-). during hypothermia reacts with available NO. to produce ONOO(-), and drug-induced O(2)(-). dismutation eliminates the hypothermia-induced increase in O(2)(-).
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PMID:Hypothermia augments reactive oxygen species detected in the guinea pig isolated perfused heart. 1464 63

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

Traumatic injury to the brain and spinal cord results in an early inflammatory response that is initiated by the release of proinflammatory cytokines followed by the infiltration and accumulation of polymorphonuclear leukocytes (PMNLs). The role of the inflammatory cascade on traumatic outcome remains controversial. Pleiotropic cytokines appear to function both protectively and destructively. The induction of cytokines can lead to the expression of the inducible form of nitric oxide synthase (iNOS), which in turn provokes the release of excessive amounts of nitric oxide (NO) that may participate in the pathogenesis of tissue injury. Hypothermia has been reported by various groups to be neuroprotective in brain and spinal cord trauma. We studied the effect of therapeutic hypothermia on cerebral IL-1beta concentrations, PMNL accumulation and iNOS activity after traumatic brain injury (TBI) and spinal cord injury (SCI). Based on current data therapeutic hypothermia may protect in models of traumatic injury by modulating deleterious inflammatory processes.
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PMID:The role of inflammatory processes in the pathophysiology and treatment of brain and spinal cord trauma. 1533 3


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