UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors examined the effects of both intermittent reperfusion and nitric oxide synthase (NOS) inhibition, caused by NG-nitro-L-arginine methyl ester (L-NAME) during episodes of focal cerebral ischemia induced to simulate the neurosurgical setting. Seventy-eight Wistar rats underwent single (60 minutes of ischemia) or repetitive (four 15-minute periods of ischemia separated by 5 minutes of reperfusion) episodes of middle cerebral artery occlusion while under anesthesia (1.0% halothane). Twenty-four hours after the procedure, the animals were given neurological examinations and then sacrificed for histological preparation and examination. The intermittent reperfusion groups tended to have smaller mean cortical infarctions. There was also a trend showing a decrease in infarction size in groups given L-NAME. The combination of intermittent reperfusion and preischemic administration of L-NAME (10 mg/kg) resulted in a 65% reduction in infarction size (p < 0.05) when compared to that caused by 60 minutes of single occlusion without L-NAME. The use of NOS inhibition combined with intermittent reperfusion may be a technique to provide intraoperative cerebral protection during neurovascular procedures that require temporary vascular occlusion.
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PMID:Effect of intermittent reperfusion and nitric oxide synthase inhibition on infarct volume during reversible focal cerebral ischemia. 766 28

Increased release of endothelium-derived relaxing factor/nitric oxide has been proposed as the final common pathway for vasodilator responses to gram-negative lipopolysaccharide (endotoxin). To test this hypothesis, we examined endothelium-dependent and endothelium-independent vasodilator agents in vascular smooth muscle isolated from guinea pigs 16 hours after injection of saline (control group) or induction of Escherichia coli endotoxemia; aortic rings (approximately 1 mm in diameter) were studied with standard isometric tension techniques. Endotoxemia resulted in a significant loss of vasodilator responses to the endothelium-dependent receptor agonists acetylcholine (10(-10)-10(-5) M) and ADP (10(-8)-10(-5) M). In contrast, endotoxemia did not affect vasodilator responses to either the endothelium-dependent receptor agonist substance P (10(-11)-10(-7) M), the endothelium-dependent and receptor-independent agonist A23187 (10(-9)-10(-6) M), or the endothelium-independent agonist nitroprusside (10(-10)-10(-4) M). The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) inhibited the vasodilator response to acetylcholine more in vessels from lipopolysaccharide-injected than control guinea pigs. Unexpectedly, L-NAME converted the endothelium-dependent vasodilator action of ADP to an endothelium-dependent vasoconstrictor response that was blocked individually by the cyclooxygenase inhibitor indomethacin, the thromboxane synthase inhibitor dazoxiben, and the thromboxane A2 receptor antagonist SQ29548. We conclude that in vivo endotoxemia inhibits the constitutive isoform of nitric oxide synthase in endothelial cells by selectively disrupting receptor-coupled activation mechanisms shared by acetylcholine and ADP. Furthermore, since L-NAME unmasks a thromboxane A2-mediated vasoconstrictor action of the endogenous purinoceptor agonist ADP, drugs that inhibit nitric oxide synthase could exacerbate sepsis-induced vasoconstriction and ischemia by synergizing with lipopolysaccharide-induced inhibition of endothelial nitric oxide synthase.
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PMID:Selective inhibition of endothelium-dependent vasodilator capacity by Escherichia coli endotoxemia. 767 34

1. Ischaemia-reperfusion injury in the kidney is associated with a loss of autoregulation, an increase in renal vascular resistance (RVR), a decrease of renal blood flow (RBF) and ultimately acute renal failure. The aim of this study was to investigate the role of the release of endogenous nitric oxide (NO) in the recovery of RBF after ischaemic injury of the renal vascular bed. 2. Anaesthetized rats (thiopentone sodium; 120 mg kg-1, i.p.) were submitted to acute renal ischaemia followed by 2 or 6 h of reperfusion (I/R). Reperfusion was associated with a significant reduction in RBF, an increase in RVR, and an impairment of the vasodilator effect of acetylcholine (ACh). 3. NG-nitro-L-arginine methyl ester (L-NAME, 30 micrograms kg-1 min-1, i.v., n = 5) significantly prevented the recovery of RBF after I/R injury. Similarly, inhibition of prostanoid formation with indomethacin (5 mg kg-1, i.v., n = 4) significantly enhanced the rise in RVR associated with I/R injury. 4. Infusion of L-arginine (L-Arg; 1 or 3 mg kg-1 min-1, i.v., n = 5 and 4, respectively) or D-Arg (1 mg kg-1 min-1, i.v., n = 6), starting 30 min after occlusion, did not improve the recovery of RBF. Furthermore, infusion of L-Arg (20 mg kg-1 min-1 for 15 min; n = 4) had no effect on the I/R-induced impairment of the vasodilator responses to ACh. 5. To elucidate the relative importance of the constitutive and inducible NO synthase isoforms for the formation of NO after I/R, calcium-dependent (constitutive) and calcium-independent (inducible) NO synthase activities were measured in kidney homogenates obtained from ischaemic or non-ischaemic kidneys. A calcium-independent NO synthase activity was not detectable in kidney homogenates obtained from either sham-operated control rats or from animals subjected to I/R. Moreover, dexamethasone(3 mg kg-1, i.v., 60 min prior to I/R, n = 6), an inhibitor of the induction of NO synthase,had no effect on either RBF or RVR in rats subjected to I/R. In contrast to I/R, lipopolysaccaride(LPS, endotoxin; 5 mg kg-1, i.p., n = 3) caused a significant induction of a calcium-independent NO synthase activity in the kidney.6. These results confirm the importance of the release of vasodilator cyclo-oxygenase metabolites in the compromised renal circulation and indicate that the formation of NO derived from the constitutive, but not the inducible NO synthase, is also important for the maintenance of RBF after I/R injury of the renal vascular bed.
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PMID:Support of renal blood flow after ischaemic-reperfusion injury by endogenous formation of nitric oxide and of cyclo-oxygenase vasodilator metabolites. 768 1

We have reported previously that posttreatment with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of the nitric oxide synthase, reduced the volume of cortical and striatal infarct induced by middle cerebral artery occlusion in rats. In the present study, we investigated the mechanisms by which L-NAME (3 mg/kg i.p.) is neuroprotective in this model of cerebral ischemia. First, we have shown the reversal of the neuroprotective effect of L-NAME by a coinjection of L-arginine. Second, in order to determine by which mechanism nitric oxide exacerbates neuronal damage produced by focal cerebral ischemia, we studied the effect of the inhibition of nitric oxide synthase by L-NAME on the histological consequences of a focal injection of N-methyl-D-aspartate (NMDA) in the striatum, and on the striatal overflow of glutamate and aspartate induced either by K+ depolarization or by focal cerebral ischemia. We have found that L-NAME treatment reduced the excitotoxic damage produced by NMDA injection. By using microdialysis, we have shown that the K(+)- and the ischemia-induced glutamate efflux was reduced by 52 and 30%, respectively, after the L-NAME treatment. These results indicate that nitric oxide synthesis induced by the NMDA receptor overstimulation is one of the major events leading to neuronal damage. One possible mechanism by which nitric oxide may contribute to the excitotoxic process is by facilitating the ischemia-induced glutamate overflow.
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PMID:Mechanisms involved in the neuroprotective activity of a nitric oxide synthase inhibitor during focal cerebral ischemia. 768 58

Cerebral ischemia in the gerbil results in early hippocampal changes, which include transient activation and/or translocation of protein kinase C (PKC), increased enzymatic activity of ornithine decarboxylase (ODC), and elevated DNA binding ability of activator protein-1 (AP1). The time-course of all three of these postischemic responses was found to be almost parallel, peaking at 3 hr after the ischemic insult. The effectiveness of known modulators of postischemic morphological outcome (MK-801, L-NAME, and gingkolides BN 52020 and BN 52021) in counteracting the induction of PKC, ODC, and AP1 formation was tested. These drugs were administrated as followed: MK-801 (a noncompetitive inhibitor of NMDA channel), 0.8 mg/kg i.p., 30 min before ischemia, and 5 min after the insult; L-NAME (competitive inhibitor of NO synthase), 10 mg/kg i.p., 30 min before ischemia, and 5 mg/kg, 5 min after ischemia; BN52020 and BN52021 (inhibitors of platelet-activating factor: PAF receptors) were administered as a suspension in 5% ethanol in water by oral route, 10 mg/kg for 3 days before ischemia. Three of these drugs, MK-801, L-NAME, and BN52021, significantly reduced ischemia-elevated activity of PKC and ODC, whereas AP1 formation was only partially attenuated. Our observations implicate the existence of different mechanism(s) for postischemic PKC and ODC activation, which in turn is engaged in AP1 induction.
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PMID:Modulation of ischemic signal by antagonists of N-methyl-D-aspartate, nitric oxide synthase, and platelet-activating factor in gerbil hippocampus. 774 16

Dopamine (DA) is released in large quantities from the striatum during cerebral ischemia. Along with excitatory neurotransmitters, DA plays a role in cellular neuronal ischemic injury. In this study we examined the role of nitric oxide (NO) in the ischemia-induced release of DA. A microdialysis probe was stereotactically placed into the corpus striatum of 16 Sprague-Dawley rats for DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) level determinations. After probe stabilization, the animals received either NG-nitro-L-arginine-methyl ester (L-NAME), a NO synthase inhibitor, or vehicle through the microdialysis probe. Temporary global forebrain ischemia was induced using bilateral carotid artery ligature tightening and controlled hemorrhagic hypotension for 15 min. L-NAME administration caused a reduction in ischemic estimated extraneuronal DA concentration by 60% (P < 0.005) compared with control. There was an increase in both DOPAC and HVA concentrations during the recovery period compared to baseline values in the control group (P < 0.05). L-NAME also caused a reduction in HVA concentration compared to vehicle administration during the latter part of recovery (P < 0.05). These data support the concept that ischemic dopamine release may be mediated by NO. This NO-modulated DA release may contribute to the previously reported deleterious neurotoxic effects of NO during ischemia.
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PMID:Nitric oxide modulates dopamine release during global temporary cerebral ischemia. 776 37

Nitric oxide, NO., exerts numerous important regulatory functions in biological tissues and has been hypothesized to have a role in the pathogenesis of cellular injury in a number of diseases. It has been suggested that alterations in NO. generation are a critical cause of injury in the ischemic heart. However, the precise alterations in NO. generation which occur are not known, and there is considerable controversy regarding whether myocardial ischemia results in increased or decreased NO. formation. Therefore, electron paramagnetic resonance studies were performed to directly measure NO. in isolated rat hearts subjected to global ischemia, using the direct NO. trap Fe(2+)-N-methyl-D-glucamine dithiocarbamate, which specifically binds NO. giving rise to a characteristic triplet EPR spectrum with g = 2.04 and aN = 13.2 G. While only a small triplet signal was observed in normally perfused hearts, a 10-fold increase in this triplet EPR spectrum was observed after 30 min of ischemia indicating a marked increase in NO. formation and trapping. Measurements were performed as a function of the duration of ischemia, and it was determined that with increased duration of ischemia NO. formation and trapping was also increased. NO. generation was inhibited by the nitric oxide synthase blocker, N-nitro-L-arginine methyl ester (L-NAME), suggesting that NO. was generated via nitric oxide synthase. Blockade of NO. generation with L-NAME resulted in more than a 2-fold increase in the recovery of contractile function in hearts reperfused after 30 min of global ischemia. Thus, ischemia causes a marked duration-dependent increase of NO. in the heart which may in turn mediate postischemic injury.
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PMID:Direct measurement of nitric oxide generation in the ischemic heart using electron paramagnetic resonance spectroscopy. 781 91

The objective of this investigation was to determine the effect of cultured human umbilical vein endothelial cells (HUVEC) on the vascular response to canine coronary arteries in which the endothelium had been either mechanically removed or injured by multiple brief episodes of occlusion and reperfusion in vivo. The endothelium-dependent vasodilator, A23187 (10(-6) mol/l) did not cause any significant relaxation in vessels from which the endothelium had been removed. However, following addition of cultured HUVEC to the tissue bath (75 x 10(3) cells/ml), A23187 produced a significant (p < 0.05) relaxation. This effect was abolished by inhibition of nitric oxide synthase with Nw-nitro-l-arginine methyl ester (L-NAME). Vascular relaxation caused by the nitric oxide donor SIN-1 was significantly (p < 0.05) enhanced when cultured HUVEC were added to vessels mechanically denuded of endothelium. Repetitive ischemia and reperfusion significantly inhibited the relaxant response to A23187. Addition of cultured HUVEC to the tissue bath partially restored the response to A23187. In contrast to the mechanically damaged vessels the relaxant response to SIN-1 was unaffected by cultured HUVEC in reperfusion-injured vessels. These results demonstrate that cultured endothelial cells partially restore endothelium-dependent vasodilation of vessels in which the endothelium is not functional following mechanical- or reperfusion-induced damage. The differential effect of endothelial cells on the response to SIN-1 suggests that mechanical and reperfusion injury alter the coronary vascular response to SIN-1 by different mechanisms.
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PMID:Cultured endothelial cells restore vasodilator responses to coronary arteries with impaired endothelial function and alter the response to a nitric oxide donor. 783 88

The purpose of this study was to evaluate potential mechanisms of ischemia-evoked amino acid transmitter release. Changes in extracellular levels of transmitter amino acids and lactic acid dehydrogenase (LDH) in rat cerebral cortex during and following four-vessel occlusion elicited global cerebral ischemia were examined using a cortical cup technique. Ischemia-evoked release of glutamate, aspartate and gamma-amino-butyric acid (GABA) was compared in control vs. drug-treated animals. Tetrodotoxin and antagonists of glutamate receptors (DNQX, MK-801, and AP-3) depressed the initial rate of increase in extracellular glutamate and aspartate without altering the total amount of these amino acids collected in the cortical superfusates. Cobalt, a calcium channel antagonist, failed to alter efflux. Acidic amino acid transport inhibitors (dihydrokainate, L-trans-PDC) depressed the rate of onset of glutamate and aspartate release and dihydrokainate depressed total release by 44%. PD 81723, an allosteric enhancer at the A1 adenosine receptor, depressed glutamate efflux, as did L-NAME, an inhibitor of nitric oxide synthase. Extracellular increases in GABA levels were depressed by tetrodotoxin and L-trans-PDC. The GABA transport inhibitor, nipecotic acid, increased the initial rate of onset of GABA release. Increases in LDH levels in the extracellular fluid became apparent during the period of ischemia and continued to increase during the subsequent 90 min of reperfusion. These results suggest that ischemia evokes a release of neurotransmitter amino acids that is only partially dependent upon Ca2+ influx activation or the reversal of amino acid transporters. Nonselective mechanisms, resulting from the disruption of plasma membrane integrity, may contribute significantly to the total ischemia-evoked release of excitatory amino acids.
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PMID:Characterization of glutamate, aspartate, and GABA release from ischemic rat cerebral cortex. 791 62

The objective of this study was to correlate nitric oxide production with time of reperfusion of the post-ischemic feline small intestine. Epithelial permeability, quantitated as blood-to-lumen clearance of 51Cr-EDTA, following 1 hr of ischemia and 4 hr of reperfusion of the small intestine, increased approximately 10-fold. This increase was further augmented by L-NAME infusion between 60 and 120 min but not at 240 min. Ca(2+)-dependent nitric oxide synthase activity was reduced by approximately 50% at 3 and 4 hr of reperfusion, whereas Ca(2+)-independent nitric oxide synthase activity was undetectable throughout the experiment. Administration of L-arginine at the start of reperfusion attenuated the reperfusion-induced epithelial barrier dysfunction for the first 120 min but not at 180 or 240 min. Continuous infusion of a nitric oxide donor (CAS 754) following 1 hr of reperfusion reduced epithelial permeability at 4 hr of reperfusion. In conclusion, a reduction in nitric oxide production was observed with time of reperfusion, possibly due to reduced nitric oxide synthase levels.
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PMID:Time course of nitric oxide production and epithelial dysfunction during ischemia/reperfusion of the feline small intestine. 802 78

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