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)

Hypercapnia elicits hypothermia in a number of vertebrates, but the mechanisms involved are not well understood. In the present study, we assessed the participation of the nitric oxide (NO) pathway in hypercapnia-induced hypothermia and hyperventilation by means of NO synthase inhibition by using Nomega-nitro-L-arginine (L-NNA). Measurements of ventilation, body temperature, and oxygen consumption were performed in awake unrestrained rats before and after L-NNA injection (intraperitoneally) and L-NNA injection followed by hypercapnia (5% CO2). Control animals received saline injections. L-NNA altered the breathing pattern during the control situation but not during hypercapnia. A significant (P < 0.05) drop in body temperature was measured after both L-NNA (40 mg/kg) and 5% inspired CO2, with a drop in oxygen consumption in the first situation but not in the second. Hypercapnia had no effect on L-NNA-induced hypothermia. The ventilatory response to hypercapnia was not changed by L-NNA, even though L-NNA caused a drop in body temperature. The present data indicate that the two responses elicited by hypercapnia, i.e., hyperventilation and hypothermia, do not share NO as a common mediator. However, the L-arginine-NO pathway participates, although in an unrelated way, in respiratory function and thermoregulation.
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PMID:Effect of nitric oxide synthase inhibition on hypercapnia-induced hypothermia and hyperventilation. 972 71

Human NTera2 teratocarcinoma cells were differentiated into postmitotic NT2-N neurons and exposed to hypoxia for 6 h. The cultures were evaluated microscopically, and percent lactate dehydrogenase (LDH) release after 24 and 48 h was used as an assay for cell death. After 48 h LDH release was 24.3 +/- 5.6% versus 13.8 +/- 3.7% in controls (p < 0.001). Cell death was greatly diminished by MK-801 pretreatment (15.4 +/- 5.1%, p < 0.001). If glutamine was omitted from the medium, glutamate levels after 6 h of hypoxia were reduced from 101 +/- 63 to 2.3 +/- 0.3 microM, and cell death at 48 h was also markedly reduced (15.4 +/- 4.5%, p < 0.001). The alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (18.7 +/- 5.1%, p < 0.001) and mild hypothermia (33.5-34 degrees C) during hypoxia (19.5 +/- 2.7%, p < 0.05) were moderately protective. Basic fibroblast growth factor (24.1 +/- 3.2%), the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (22.8 +/- 8.1%), the antioxidant N-tert-butyl-o-phenyinitrone (18.9 +/- 5.9%), and the 21-aminosteroid U74389G (24.0 +/- 3.4%) did not protect the cells. N-Acetyl-L-cysteine even tended to increase cell death (30.1 +/- 2.5%, p = 0.06). Treatment with MK-801 at the end of hypoxia did not reduce cell death (23.3 +/- 2.3%). In separate experiments, a 15-min exposure to 1 mM glutamate without hypoxia did not result in significant cell death (14.7 +/- 2.4 vs. 12.2 +/- 2.1%, p = 0.07). We conclude that, although somewhat resistant to glutamate toxicity when normoxic, NT2-N neurons die via an ionotropic glutamate receptor-mediated mechanism when exposed to hypoxia in the presence of glutamate. As far as we know, this is the first reported analysis of the mechanism of hypoxic cell death in cultured human neuronlike cells.
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PMID:Hypoxic cell death in human NT2-N neurons: involvement of NMDA and non-NMDA glutamate receptors. 975 Nov 88

It has been reported that arginine vasopressin (AVP) plays a thermoregulatory action, but very little is known about the mechanisms involved. In the present study, we tested the hypothesis that nitric oxide (NO) plays a role in systemic AVP-induced hypothermia. Rectal temperature was measured before and after AVP, AVP blocker, or NG-nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor) injection. Control animals received saline injections of the same volume. The basal body temperature (Tb) measured in control animals was 36.53 +/- 0.08 degreesC. We observed a significant (P < 0.05) reduction in Tb to 35.44 +/- 0.19 degreesC after intravenous injection of AVP (2 micrograms/kg) and to 35.74 +/- 0. 10 degreesC after intravenous injection of L-NAME (30 mg/kg). The systemic injection of the AVP blocker [beta-mercapto-beta, beta-cyclopentamethylenepropionyl1,O-Et-Tyr2,Val4,Arg8]vasopressin (10 micrograms/kg) caused a significant increase in Tb to 37.33 +/- 0.23 degreesC, indicating that AVP plays a tonic role by reducing Tb. When the treatments with AVP and L-NAME were combined, systemically injected L-NAME blunted AVP-induced hypothermia. To assess the role of central thermoregulatory mechanisms, a smaller dose of L-NAME (1 mg/kg) was injected into the third cerebral ventricle. Intracerebroventricular injection of L-NAME caused an increase in Tb, but when intracerebroventricular L-NAME was combined with systemic AVP injection (2 micrograms/kg), no change in Tb was observed. The data indicate that central NO plays a major role mediating systemic AVP-induced hypothermia.
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PMID:Role of nitric oxide in systemic vasopressin-induced hypothermia. 975 20

We investigated the effects of therapeutic hypothermia (30 degrees C) on alterations in constitutive (cNOS) and inducible (iNOS) nitric oxide synthase activities following traumatic brain injury (TBI). Male Sprague-Dawley rats were anesthetized with 0.5% halothane and underwent moderate (1.8-2.2 atm) parasagittal fluid-percussion (F-P) brain injury. In normothermic rats (37 degrees C) the enzymatic activity of cNOS was significantly increased at 5 min within the injured cerebral cortex compared with contralateral values (286.5+/-68.9% of contralateral value; mean+/-SEM). This rise in nitric oxide synthase activity was significantly reduced with pretraumatic hypothermia (138.8+/-17% of contralateral value; p < 0.05). At 3 and 7 days after normothermic TBI the enzymatic activity of cNOS was decreased significantly (30+/-8.4 and 28.6+/-20.9% of contralateral value, respectively; p < 0.05). However, immediate posttraumatic hypothermia (3 h at 30 degrees C) preserved cNOS activity at 3 and 7 days (69.5+/-23.3 and 78.6+/-7.6% of contralateral value, respectively; mean+/-SEM; p < 0.05). Posttraumatic hypothermia also significantly reduced iNOS activity at 7 days compared with normothermic rats (0.021+/-0.06 and 0.23+/-0.06 pmol/mg of protein/min, respectively; p < 0.05). The present results indicate that hypothermia (a) decreases early cNOS activation after TBI, (b) preserves cNOS activity at later periods, and (c) prevents the delayed induction of iNOS. Temperature-dependent alterations in cNOS and iNOS enzymatic activities may participate in the neuroprotective effect of hypothermia in this TBI model.
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PMID:Effects of moderate hypothermia on constitutive and inducible nitric oxide synthase activities after traumatic brain injury in the rat. 1021 83

The present experiments examined the impact of manipulating the NO system on production of isolation-induced ultrasonic vocalizations (USVs) in 10- and 11-day-old rat pups. Pups were tested under both high- and low-baseline USV emission; the latter was accomplished by pretest administration of cocaine, a drug known to suppress USVs. Treatment with 10, 50, or 100 mg/kg (but not 1 mg/kg) of the nitric oxide synthase (NOS) inhibitor L-nitro-arginine methyl ester (L-NAME) significantly attenuated USV production, as did injection of 10 mg/kg cocaine; combined treatment with both drugs did not result in greater suppression, perhaps due to a floor effect. Although cocaine increased locomotor activity, treatment with L- or D-NAME alone did not alter activity levels. Exposure to L-NAME induced some hypothermia, although these alterations in body temperature were not systematically related to the drug-induced suppression of USVs. Alterations in USV production by L-NAME were not evident after pretreatment with the less active isomer D-NAME, evidence supporting the importance of NO synthesis inhibition per se in the marked L-NAME-induced suppression of USVs in isolated infant rats.
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PMID:Inhibition of nitric oxide synthesis with L-NAME suppresses isolation-induced ultrasounds in rat pups. 1034 May 23

Because it has been recently suggested that nitric oxide (NO) may mediate the effects of hypoxia on body temperature and ventilation, the present study was designed to assess more completely the effects of a neuronal NO synthase inhibitor (7-nitroindazole, 25 mg/kg ip), at ambient temperature of 26 and 15 degrees C, on the ventilatory (V), metabolic (O(2) consumption), and thermal changes (colonic and tail temperatures) induced by ambient hypoxia (fractional inspired O(2) of 11%) or CO hypoxia (fractional inspired CO of 0.07%) in intact, unanesthetized adult rats. At both ambient temperatures, 7-nitroindazole decreased oxygen consumption, colonic temperature, and V in normoxia. The drug reduced ambient or CO hypoxia-induced hypometabolism and ventilatory response, but the hypothermia persisted. It is concluded that NO arising from neural NO synthase plays an important role in the control of metabolism and V in normoxia. As well, it mediates, in part, the hypometabolic and the ventilatory response to hypoxia. The results are consistent with the notion that central nervous system hypoxia resets the thermoregulatory set point by decreasing brain NO.
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PMID:Role of nitric oxide in hypoxic hypometabolism in rats. 1040 63

Intraoperative mild hypothermia is common. We have investigated the effects of mild hypothermia (34 vs 38 degrees C) on phenylephrine--(10(-8) to 10(-5) mol litre-1) induced contractions of rat aortic rings mounted for isometric tension recordings. A marked decrease in Emax (maximal tension) (P < 0.05) and significant increase in EC50 (phenylephrine concentration producing 50% of maximal tension) were observed at the lower temperature in endothelium intact rings, but there was no effect of temperature when the endothelium had been removed. The decreased contraction with hypothermia in the endothelium intact vessels was restored to 84% by administration of the nitric oxide synthase inhibitor L-NNA and a small additional amount of tone was restored in the presence of the cyclooxygenase inhibitor, indomethacin. We conclude that mild hypothermia markedly decreased phenylephrine-induced rat aortic contraction in vitro by endothelium dependent mechanisms, largely related to increased nitric oxide production or action.
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PMID:Effect of mild hypothermia on the vascular actions of phenylephrine in rat aortic rings. 1056 95

Studies concerning neurotransmitter release following cerebral hypoxia are scarce, and the effects of mild hypothermia on hypoxia-induced neurotransmitter release are unknown. The purpose of this study was to investigate changes in excitatory amino acid (EAA) concentrations and nitric oxide (NO) synthesis following cerebral hypoxia in rats, and the effects of mild hypothermia on both. Cerebral hypoxia (PaO2, 30-40 mm Hg) was induced in each rat for 60 min. Cerebral blood flow (CBF) was measured by laser-Doppler flowmetry, and the extracellular concentrations of EAAs and NO end-products (nitrite and nitrate) were measured by in vivo microdialysis in normothermic (37 degrees C) and hypothermic (32 degrees C) rats. In both groups, CBF showed modest increases during hypoxia and returned to baseline during reoxygenation. The EAA levels of the normothermic rats increased markedly after hypoxia induction and returned to baseline levels during reoxygenation. Hypothermia abolished these increases completely. The NO end-product levels under normothermic conditions declined slightly during hypoxia, and then increased transiently during reoxygenation. Hypothermia appeared to attenuate the NO end-product level and to delay the peak. When the relationship between glutamate and the NO end-products was examined on an individual-animal basis, glutamate release did not parallel NO synthesis. The results indicate that hypothermic neuroprotection during cerebral hypoxia may be attributable to the amelioration of damage by reduction of presynaptic EAA release. Although it is unclear from the present results alone whether endothelial NO synthase, neuronal NO synthase or both caused the elevation of the NO end-products during reoxygenation, it is possible that the attenuation and delay of the peak of the NO end-product level plays a role in protection from NO-induced neuronal damage.
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PMID:Effects of mild hypothermia on the cortical release of excitatory amino acids and nitric oxide synthesis following hypoxia. 1059 24

Hypoxia causes a regulated decrease in body temperature (T(b)), and nitric oxide (NO) is now known to participate in hypoxia-induced hypothermia. Hypoxia also inhibits lipopolysaccharide (LPS)-induced fever. We tested the hypothesis that NO may participate in the hypoxia inhibition of fever. The rectal temperature of awake, unrestrained rats was measured before and after injection of LPS, with or without concomitant exposure to hypoxia, in an experimental group treated with N(omega)-nitro-L-arginine (L-NNA) for 4 consecutive days before the experiment and in a saline-treated group (control). L-NNA is a nonspecific NO synthase inhibitor that blocks NO production. LPS caused a dose-dependent typical biphasic rise in T(b) that was completely prevented by hypoxia (7% inspired oxygen). L-NNA caused a significant drop in T(b) during days 2-4 of treatment. When LPS was injected into L-NNA-treated rats, inhibition of fever was observed. Moreover, the effect of hypoxia during fever was significantly reduced. The data indicate that the NO pathway plays a role in hypoxia inhibition of fever.
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PMID:Role of nitric oxide in hypoxia inhibition of fever. 1060 Nov 66

Cerebral hypoxia-ischemia in the perinatal period continues to be a major contributor to chronic neurologic impairment in children worldwide. Extensive research conducted in the past several years has led to a better understanding of the mechanisms involved in hypoxic-ischemic brain injury. Based on this understanding, the major potential therapeutic approaches being studied include antagonists of excitatory amino acids, calcium channel antagonists, free-radical scavengers, nitric oxide synthase inhibitors, anti-inflammatory agents, trophic factors, and hypothermia. Several agents are in clinical trial phases in adults. However, safety concerns and close relationship between pathomechanisms of hypoxic-ischemic cerebral injury and normal developmental processes have contributed to the slow pace in the neonatal trials. Large multicenter trials including an adequate number of infants will be needed to evaluate efficacy of therapeutic interventions in this particular age group. A large number of risk factors that predispose to hypoxic ischemic injury have been identified. It is important to control these factors and prevent brain damage in the first place. This is especially true for developing countries where resources for treatment with newer agents (when they become available) are likely to be limited. Recent information regarding mechanisms of injury and potential therapeutic measures related to perinatal age are presented in this paper.
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PMID:Hypoxic-ischemic brain damage in perinatal age group. 1079 99


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