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

The research studied the concentration variation of peroxynitrite anion (O=N-O-O-) released from cultured neonatal myocardial cells induced by ischemia/reperfusion and studied the protective effect of melatonin on the injury. For this purpose, amperometry peroxynitrite ultramicrosensors (UMS) were fabricated and constructed by electropolymerizing inorganic macromolecular film of tetraaminophthalocyanine manganese(II) and coating chemically with poly(4-vinylpyridine). Under optimum conditions, the UMS showed high selectivity and sensitivity to peroxynitrite determination with a calculated detection limit of 1.8 x 10(-8) mol/L (S/N of 3). The detection of peroxynitrite was based on electrocatalytic reduction of peroxynitrite. The mechanism of catalysis was also discussed. The UMS should be promising for in vivo measurement of peroxynitrite without interference or fouling. Peroxynitrite released from myocardial cells both in the ischemic period and in the reperfusion period was measured directly. This approach may lead to important information for myocardial cells on the mechanism of injury and prospective treatments of medicine such as melatonin.
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PMID:Amperometric ultramicrosensors for peroxynitrite detection and its application toward single myocardial cells. 1108 Aug 82

The formation of peroxynitrite and nitrotyrosine was examined in a variety of in vitro and in vivo animal models and its relation to cell or tissue damage was examined. polymorphonuclear leukocyte (PMN)-induced injury to cardiac myocytes endothelial cells, activated PMN produced peroxynitrite. Peroxynitrite appears to be responsible for the injury but it was not a major mediator of endothelial cell injury. In the experiment of ischemia-reperfusion injury of the rat brain nitrotyrosine was formed in the peri-infarct and core-of infarct regions. The degradation curve of nitrotyrosine revealed that its t(1/2) was about 2.2 hours. In the radiation-induced lung injury of rats, nitrotyrosine was also formed but it was not the sole mechanism for the injury. Levels of nitrotyrosine correlated with the severity of myocardial dysfunction in the canine model of cytokine-induced cardiac injury. Inhibition of NO generation abolished the formation of peroxynitrite and nitrotyrosine in all experiments. In conclusion; although nitrotyrosine is formed in a variety of pathological conditions where the generation of NO is increased, its presence does not always correlate with the severity of injury.
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PMID:Nitrotyrosine formation and its role in various pathological conditions. 1123 99

Hepatic blood flow decreases under cholestasis and there is evidence that NO regulates liver microvascular perfusion. Thus, the aim of the present study was to evaluate NO synthesis in cholestasis. Cholestasis was induced by bile-duct ligation (BDL) in male Wistar rats. Bilirubins and enzyme activities were measured in serum. Lipid peroxidation, GSH, GSSG and glycogen were determined in liver. Histopathological analysis was performed. Serum NO2- + NO3- concentration was measured by the Gries reaction. iNOS immunoblot analysis was carried out using an iNOS polyclonal antibody. After 7 days of BDL lipid peroxidation increased while GSH/GSSG ratio decreased. Serum NO2- + NO3- and liver iNOS protein were reduced, accompanied by ischemia as revealed by the histopathological analysis. GSH upregulates NO synthesis by increasing iNOS mRNA levels and iNOS activity, thus the reduction of GSH/GSSG ratio may be responsible for the downregulation of iNOS protein and NO synthesis, which in turn may explain the observed ischemia and the decreased hepatic blood perfusion in cholestasis reported by others.
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PMID:Nitric oxide and inducible nitric oxide synthase expression are downregulated in acute cholestasis in the rat accompanied by liver ischemia. 1124 95

The increase of radical forms of mitochondrial respiratory chain compounds (MRCC) is an indicator of an increased risk of the formation of oxygen radicals. Using electron paramagnetic resonance (EPR), we found an increase of signals corresponding to ubisemichinone radical (.QH) and ironsulfur proteins radical forms (-FeS) of these respiratory chain compounds during ischemia in the isolated perfused rat heart (.QH increased from 1.51 to 3.08, .FeS1 from 1.14 to 2.65 arbitrary units). During the 5-min reperfusion, the signals returned to normoxic levels. In isolated mitochondria exposed to anoxia and reoxygenation the radical forms of .QH and FeS2 changed in a similar manner as in the intact heart. A combination of in vivo captopril treatment and in vitro L-arginine administration significantly decreased the levels of MRCC radicals in the isolated myocardium (.QH from 2.61 to 1.72 and .FeS, from 1.82 to 0.46 under normoxia; .QH from 4.35 to 2.66 and .FeS1 from 1.93 to 1.35 during ischemia). This decrease in MRCC radical forms was associated with increased NO levels in the perfusate, determined as NO2- / NO3-, as well as tissue NO levels determined using EPR as the dinitrosyl iron complex (DNIC). These results provide new information about the cardioprotective effects of ACE inhibitors and L-arginine.
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PMID:The effect of captopril on nitric oxide formation and on generation of radical forms of mitochondrial respiratory chain compounds in ischemic rat heart. 1170 52

Reactive oxygen species are reactive, partly reduced derivatives of molecular oxygen. Important reactive oxygen species in biological systems include superoxide radical anion, hydrogen peroxide, and hydroxyl radical. Peroxynitrite, is another important species in biological systems. A variety of enzymatic and non-enzymatic processes can generate reactive oxygen species in mammalian cells. An extensive body of experimental evidence from studies using animal models supports the view that reactive oxygen species are important in the pathogenesis of ischemia-reperfusion syndromes, sepsis, acute respiratory distress syndrome, and multiple organ dysfunction syndrome. This view is further supported by data from clinical studies that correlate biochemical evidence of reactive oxygen species-mediated stress with the development of acute respiratory distress syndrome or sepsis in patients. Ethyl pyruvate, a simple derivative of pyruvic acid, has been shown to be efficacious in several animal models of critical illness, and warrants further evaluation in this regard.
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PMID:Reactive oxygen species as mediators of organ dysfunction caused by sepsis, acute respiratory distress syndrome, or hemorrhagic shock: potential benefits of resuscitation with Ringer's ethyl pyruvate solution. 1184 84

In the last decade it has become well established that in the skin, nitric oxide (NO), a diffusable gas, mediates various physiologic functions ranging from the regulation of cutaneous blood flow to melanogenesis. If produced in excess, NO combines with superoxide anion to form peroxynitrite (ONOO-), a cytotoxic oxidant that has been made responsible for tissue injury during shock, inflammation and ischemia-reperfusion. The opposite effects of NO and ONOO- on various cellular processes may explain the 'double-edged sword' nature of NO depending on whether or not cellular conditions favour peroxynitrite formation. Peroxynitrite has been shown to activate the nuclear nick sensor enzyme, poly(ADP-ribose) polymerase (PARP). Overactivation of PARP depletes the cellular stores of NAD+, the substrate of PARP, and the ensuing 'cellular energetic catastrophy' results in necrotic cell death. Whereas the role of NO in numerous skin diseases including wound healing, burn injury, psoriasis, irritant and allergic contact dermatitis, ultraviolet (UV) light-induced sunburn erythema and the control of skin infections has been extensively documented, the intracutaneous role of peroxynitrite and PARP has not been fully explored. We have recently demonstrated peroxynitrite production, DNA breakage and PARP activation in a murine model of contact hypersensitivity, and propose that the peroxynitrite-PARP route represents a common pathway in the pathomechanism of inflammatory skin diseases. Here we briefly review the role of NO in skin pathology and focus on the possible roles played by peroxynitrite and PARP in various skin diseases.
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PMID:Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skin. 1210 57

A timed profile of glutathione oxidation and reactive nitrogen species during reperfusion after cerebral ischemia in rat was obtained. Dialysate was collected every 25 min from a microdialysis probe inserted into the cerebral cortex before and after cerebral ischemia. NO2-, NO3-, and reduced and oxidized glutathione (GSH, GSSG) were detected by high-performance liquid chromatography. GSH and GSSG increased and reached a peak: 3408 +/- 1710% (mean +/- SE) at 25 min of reperfusion (P < 0.0001) and 329 +/- 104% at 50 min of reperfusion (P = 0.06), respectively. Oxidation ratio decreased from 0.82 +/- 0.04 to 0.42 +/- 0.07 (P < 0.0001) at 25 min of reperfusion. NO3- levels significantly decreased (68.3 +/- 9.1%) (P < 0.01) during ischemia and remained lower than the control value during reperfusion. NO2- levels did not significantly change. These data suggest that GSH releases during early phase of reperfusion and that its rapid oxidation contributes to prevent an increase in reactive nitrogen species.
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PMID:Relationship between oxidation of glutathione and reactive nitrogen species during the early-reperfusion phase of cerebral ischemia. 1219 54

Tyrosine nitration is a common modification to proteins in vivo, but the reactive nitrogen species responsible for nitration are often studied in vitro using just the amino acid tyrosine in simple phosphate solutions. To investigate which reactive nitrogen species could nitrate proteins in a complex biological system, we exposed rat heart and brain homogenates to peroxynitrite, nitric oxide under aerobic conditions, and other putative nitrating agents. Peroxynitrite was by far the most efficient nitrating agent when alternative targets were available to compete with tyrosine. Curiously, proteins in heart homogenates were substantially more resistant to nitration than brain homogenates. Ultrafiltration to remove low molecular weight compounds made the heart proteins equally susceptible as the brain proteins to nitration. Endogenous ascorbate and free thiols had little effect on nitration by peroxynitrite in either heart or brain. However, accumulation of urate formed by the oxidation of hypoxanthine by xanthine dehydrogenase and oxidase in heart appeared to be the major inhibitor of nitration. Heart homogenates treated with uricase, which converts urate to allantoin, showed equivalent nitration as in brain homogenates. Urate, as assayed by HPLC, was 58 +/- 8 microM in heart but only 4 +/- 2 microM in brain homogenates. Although xanthine dehydrogenase conversion to a free radical-producing oxidase can serve as an important source of superoxide and hydrogen peroxide during ischemia/reperfusion, our results suggest that urate formation by xanthine dehydrogenase may provide a significant antioxidant defense against peroxynitrite and related nitric oxide-derived oxidants.
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PMID:Urate produced during hypoxia protects heart proteins from peroxynitrite-mediated protein nitration. 1239 32

Peroxynitrite generated in arteries from superoxide and NO may damage Ca(2+) pumps. Here, we report the effects of peroxynitrite on ATP-dependent azide-insensitive uptake of Ca(2+) into pig coronary artery vesicular membrane fractions F2 [enriched in plasma membrane (PM)] and F3 [enriched in sarcoplasmic reticulum (SR)]. Membranes were pretreated with peroxynitrite and then with DTT to quench this agent. This pretreatment inhibited Ca(2+) uptake in a peroxynitrite concentration-dependent manner, but the effect was more severe in F3 than in F2. The inhibition was thus not overcome by excess DTT used to quench peroxynitrite and was not affected if catalase, SOD, or mannitol was added along with peroxynitrite. Such damage to the pump protein would be difficult to repair if produced during ischemia-reperfusion. The acylphosphates formed with ATP in F3 corresponded mainly to the SR Ca(2+) pump (110 kDa), but in F2 both PM (140 kDa) and 110-kDa bands were observed. Peroxynitrite treatment of F2 inhibited only the 110-kDa band. Inhibition of Ca(2+) uptake and acylphosphate formation from ATP correlated well in peroxynitrite-treated F3 samples. However, inhibition of acylphosphates from orthophosphate (reverse reaction of the pump) was slightly poorer. Peroxynitrite treatment also covalently cross-linked the pump protein, yielding no dimers but only larger oligomers. In contrast, cross-linking of the SR Ca(2+) pump in skeletal and cardiac muscles gives dimers as the first oligomers. Therefore, we speculate that SERCA2 has a different quaternary structure in the coronary artery smooth muscle.
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PMID:Effects of peroxynitrite on sarcoplasmic reticulum Ca2+ pump in pig coronary artery smooth muscle. 1252 49

We have investigated the role of tyrosine kinase in the antiarrhythmic effects of peroxynitrite preconditioning in rat isolated heart by using a tyrosine phosphatase inhibitor, sodium orthovanadate, and tyrosine kinase inhibitors, genistein and tyrphostin. Rat hearts were preconditioned by peroxynitrite administration at 1 microM for 3 min, which was followed by 10-min washout and 30 min of ischemia. None of the hearts had ventricular fibrillation in the peroxynitrite preconditioning group (from 64%, n=11, to 0%, n=11). Neither sodium orthovanadate (10 microM) nor genistein (50 microM) or tyrphostin (100 microM) alone showed any effects on arrhythmias. Peroxynitrite preserved its beneficial effects on arrhythmias (to 0% ventricular fibrillation, n=7) during sodium orthovanadate infusion (for 23 min) prior to 30 min of an ischemic period. On the other hand, genistein or tyrphostin treatment significantly reversed the protective effects of the peroxynitrite preconditioning (to 71% ventricular fibrillation, n=14, genistein and, to 75% ventricular fibrillation, n=8, tyrphostin). These results suggest that the tyrosine kinase pathway plays a significant role in peroxynitrite-induced preconditioning in rat isolated heart.
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PMID:Involvement of tyrosine kinase in peroxynitrite-induced preconditioning in rat isolated heart. 1262 May 10


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