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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress is a key process involved in the action of several therapeutic modalities used in cancer treatment. Ischemia reperfusion insult provides a model system for investigating the processes involved in determining the sensitivity of tumor tissue to oxidative stress. We have investigated the response of the murine CaNT tumor to ischemia reperfusion injury and the role that oxygen radicals and nitric oxide may play in this phenomenon. Our results show that little or no cell kill is detected in tumors exposed to up to 3 h of ischemia if the tumors are excised immediately before reperfusion. However, if reperfusion is permitted, then extensive cell kill is evident 24 h later. i.v. administration of superoxide dismutase or catalase, at the time when vascular reperfusion occurred, resulted in a significant protection against tumor cell kill, suggesting that the damage was mediated by oxygen radicals. Conversely, administration of an inhibitor of nitric oxide synthase, N omega-nitro-L-arginine, resulted in potentiation of tumor cell damage. Administration of a nitric oxide (NO) donor, diethylamine NO, at the time when vascular reperfusion occurred resulted in significant protection against tumor damage. These results suggest that nitric oxide is a potent mediator in determining tumor damage after ischemia reperfusion injury. The role of intrinsic NO production by murine tumors was investigated by measuring the accumulation of nitrate in the medium of tumor explants cultured in vitro in two tumors with differing sensitivity to ischemia reperfusion damage. The clamp-insensitive tumor SaS showed a greater nitrate accumulation than the clamp-sensitive tumor CaNT, which may confer a greater capacity for preventing tumor and endothelial cell damage after oxidative stress.
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PMID:Ischemia reperfusion injury in tumors: the role of oxygen radicals and nitric oxide. 852 86

There is increasing evidence that endothelium-derived nitric oxide production is an important mechanism contributing to the regulation of myocardial perfusion during ischemia distal to a coronary stenosis. Studies in conscious chronically instrumented animals have extended observations in isolated arterioles to demonstrate that inhibiting nitric oxide synthase with L-arginine analogs increases the vulnerability of the myocardium to ischemia. The variable extent to which endothelium-dependent function is impaired in human atherosclerosis raises the possibility that abnormalities in resistance vessel control contribute to the functional significance of a fixed epicardial coronary stenosis. This may explain the wide variability between the physiological effects of a given coronary stenosis and its angiographic severity. Aggressive intervention to normalize endothelium-dependent vasodilation and local nitric oxide release may have beneficial effects on the functional significance of a coronary stenosis.
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PMID:Modulation of coronary autoregulatory responses by endothelium-derived nitric oxide. 853 43

Using microdialysis, we evaluated temporal changes in striatal extracellular cGMP level following ischemia and its relationship to nitric oxide (NO) production. In untreated animals, significant elevation of cGMP was observed during ischemia and during 4 h of recirculation. In animals treated with L-NAME ischemia induced a modest increase in the cGMP level, but this level was significantly lower than that observed in the untreated animals. These results demonstrate first, that the microdialysis technique can be used to detect changes in extracellular cGMP levels during ischemia and second, that ischemia and recirculation induce a rise in cGMP which is diminished by nitric oxide synthase inhibition, suggesting a linkage to NO production.
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PMID:Ischemia-induced changes in extracellular levels of striatal cyclic GMP: role of nitric oxide. 854 96

The polyamines are involved in repair processes after intestinal ischemia. Arginine and ornithine, both precursors of polyamines were therefore expected to exert beneficial effects on mucosal barrier dysfunction. Arginine may also generate NO and there is support for the view that NO may be beneficial after an ischemic insult. Male Wistar rats were given, by gavage, isonitrogenous solutions of L-arginine (0.5 g/kg) or L-ornithine (0.7 g/kg) 17 and 2 h before ischemia. Controls received an isonitrogenous solution of casein hydrolysate (1 g/kg). Transient intestinal ischemia was produced in anesthetized rats by occluding the superior mesenteric artery for 90 min. Intestinal morphology, hydrolase activities, polyamine and cGMP contents, and cell proliferation rates were determined 4 h after reperfusion. Administration of arginine or ornithine did not prevent ischemic damage but accelerated morphological repair, enhanced cell proliferation, and polyamine content was observed. Arginine was significantly more effective than ornithine. Formation of cGMP was enhanced after arginine administration. NG-nitroarginine methylester, an inhibitor of NO synthase, prevented the arginine effects on mucosal repair. We conclude that arginine-derived NO is an important mediator in the restitution of intestinal mucosa by minimizing cell injury during reperfusion.
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PMID:Beneficial effects of L-arginine on intestinal epithelial restitution after ischemic damage in rats. 854 84

The aging process is known to be associated with profound changes in the heart. To determine whether resistance of coronary endothelial and vascular smooth muscle function to ischemia may be related to age, four groups of rats (n = 6 in each group) of different ages (1, 5, 15, and 26 months) were subjected to cardioplegic arrest for 4 hours at 4 degrees C. The postischemic basal release of nitric oxide by endothelium, as assessed by the percentage loss of coronary flow in response to 0.5 mmol/L L-monomethylarginine, an inhibitor of nitric oxide synthase, was as follows: (mean +/- standard error of the mean): 87.1% +/- 1.7%, 81.2% +/- 2.3%, 79.6% +/- 1.9%, and 74.9% +/- 2.4% in groups 1, 2, 3, and 4, respectively. Stimulated release of nitric oxide, as assessed by percentage increase of coronary flow to 10(-5) mmol/L 5-hydroxytryptamine, an endothelium-dependent vasodilator, was as follows (mean +/- standard error of the mean): 88.3% +/- 1.5%, 83.4% +/- 2.4%, 71.1% +/- 2.7%, and 63.1% +/- 3.3% in groups 1, 2, 3, and 4, respectively. Significant differences were found between each group (p < 0.05) for both basal and stimulated release of nitric oxide. Vascular smooth muscle function, as assessed by the percentage increase in coronary flow in response to glyceryl trinitrate, an endothelium-independent vasodilator, was (mean +/- standard error of the mean): 96.7% +/- 2.1%, 92.3% +/- 5.2%, 92.9% +/- 5.0%, and 98.1% +/- 2.4% in groups 1, 2, 3, and 4 respectively. No significant difference was found between groups (p = not significant). In a protocol mimicking conditions for transplantation, the postischemic recovery of the basal and stimulated release of nitric oxide, but not vascular smooth muscle function, diminished with age.
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PMID:Aging reduces postischemic recovery of coronary endothelial function. 855 71

Retinal ischemia induces a large increase in the release of glutamate, which exerts its toxic action by way of NMDA (N-methyl-D-aspartate) receptors onto amacrine cells and retinal ganglion cells. Glutamate released during ischemia and especially during reperfusion first stimulates non-NMDA receptors and depolarizes the retinal neurons. As the membrane potentials are depolarized more from the resting membrane potentials, the blockade of NMDA receptors induced by Mg2+ was released. Ca(2+)-influx through the NMDA receptors activates nitric oxide synthase of some amacrine cells, which produce nitric oxide (NO). NO at low concentrations inhibits the NMDA receptors and thereby prevents from retinal neuronal death. By contrast, NO at higher concentrations, interacting with oxygen radicals, becomes toxic and mediates glutamate-induced delayed retinal neuronal death.
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PMID:[The role of nitric oxide in the ischemic retina]. 857 55

The results of our continuing studies on the role of nitric oxide (NO) in cellular mechanisms of ischemic brain damage as well as related reports from other laboratories are summarized in this paper. Repetitive ip administration of NG-nitro-L-arginine (L-NNA), a NO synthase (NOS) inhibitor, protected against neuronal necrosis in the gerbil hippocampal CA1 field after transient forebrain ischemia with a bell-shaped response curve, the optimal dose being 3 mg/kg. Repeated ip administration of L-NNA also mitigated rat brain edema or infarction following permanent and transient middle cerebral artery (MCA) occlusion with a U-shaped response. The significantly ameliorative dose-range and optimal dose were 0.01-1 mg/kg and 0.03 mg/kg, respectively. Studies using a NO-sensitive microelectrode revealed that NO concentration in the affected hemisphere was remarkably increased by 15-45 min and subsequently by 1.5-4 h after MCA occlusion. Restoration of blood flow after 2 h-MCA occlusion resulted in enhanced NO production by 1-2 h after reperfusion. Administration of L-NNA (1 mg/kg, ip) diminished the increments in NO production during ischemia and reperfusion, leading to a remarkable reduction in infarct volume. In brain microvessels obtained from the affected hemisphere, Ca(2+)-dependent constitutive NOS (cNOS) was activated significantly at 15 min, and Ca(2+)-independent inducible NOS (iNOS) was activated invariably at 4 h and 24 h after MCA occlusion. Two hour reperfusion following 2 h-MCA occlusion caused more than fivefold increases in cNOS activity with no apparent alterations in iNOS activity. Thus, we report here based on available evidence that there is good reason to think that NOS activation in brain microvessels may play a role in the cellular mechanisms underlying ischemic brain injury.
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PMID:Nitric oxide synthase in cerebral ischemia. Possible contribution of nitric oxide synthase activation in brain microvessels to cerebral ischemic injury. 857 40

In the present study, NADPH-diaphorase histochemistry was used to assess the temporal evolution of the number of nitric oxide (NO)-synthase containing neurones after reversible focal cerebral ischaemia in rats. The number of NADPH-diaphorase containing neurones was reduced by 50% and 90% respectively 6 and 24 h after ischaemia. L-NAME, a NO-synthase inhibitor, prevented the loss of NADPH-diaphorase containing neurones observed 6 h after ischemia but not 24 h after ischaemia, suggesting that in the early phase, nitric oxide is involved in this phenomenon.
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PMID:Loss of NADPH-diaphorase containing neurones after reversible focal ischaemia in rats delayed by L-NAME. 858 Dec 65

To elucidate the mechanisms of ischemic cell damage, biochemical disturbances developing during and following in vitro ischemia of 5, 10 or 15 min duration were compared in hippocampal slices prepared from gerbil and rat brains. During ischemia the release of glutamate from slices into the medium was determined, and after ischaemia and 10 min of recovery slices were analyzed for ATP levels, adenylate energy charge and cGMP content. The release of glutamate into the medium during in vitro ischemia and the recovery of energy metabolism determined after 10 min of recovery was almost identical in slices prepared from gerbil and rat hippocampi. In contrast, cGMP levels measured 10 min following in vitro ischemia were significantly higher in gerbil as compared to rat slices. Since after 10 min of recovery following in vitro ischemia, cGMP levels reflect nitric oxide (NO) synthesis (inhibition by NO synthase blocker), it is concluded that increased NO synthesis may contribute to the higher sensitivity of the gerbil as compared to the rat hippocampus towards transient ischemia.
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PMID:Comparison of biochemical disturbances in hippocampal slices of gerbil and rat during and after in vitro ischemia. 858 22

We performed experiments to investigate the participation of nitric oxide (NO) in the delayed neuronal death (DND) of gerbil hippocampal CA1 neurons, following 5-min forebrain ischemia with pretreatment of stereotaxic intraventricular administration of several types of NO synthase inhibitors and biologically inactive control drugs. The number of surviving neurons in the control drug groups administered NG-monomethyl-D-arginine or NG-nitro-D-arginine methyl ester was comparable to that in the group administered artificial cerebro-spinal fluid, while the groups administered NOS inhibitors, such as NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester, showed significant preservation of the neuronal densities compared with the control drug groups, to over 60% of the sham operation group value. Furthermore, intraventricular administration of N omega-nitro-L-arginine at various concentrations disclosed a dose-dependent protection against the DND. These results suggest that the generation of NO may act to promote the establishment of DND.
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PMID:Intraventricular administration of nitric oxide synthase inhibitors prevents delayed neuronal death in gerbil hippocampal CA1 neurons. 858 29


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