Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The contribution of nitric oxide (NO) to ischemic acute renal failure is unclear. Because polymorphonuclear neutrophils (PMN) accentuate injury in kidneys subjected to ischemia-reperfusion and because NO has potent vascular and PMN effects, we examined the contribution of NO to PMN-mediated injury in isolated perfused rat kidneys. Nonischemic and ischemic kidneys were perfused by the isolated kidney technique in the presence or absence of PMN and NO agonists [sodium nitroprusside (SNP), L-arginine (L-Arg)] or a NO synthase inhibitor [N omega-nitro-L-arginine (L-NNA)]. In nonischemic kidneys, the NOS antagonist decreased perfusion flow rate by 25% without affecting glomerular filtration rate (GFR) or tubular sodium reabsorption (TNa), whereas NOS agonist treatment had no effects. After 20 min of ischemia/60 min reperfusion in the absence of PMN NO agonist treatment potentiated ischemia-reperfusion-induced loss of GFR and TNa, whereas adding the NO antagonist lessened glomerular and tubular injury. Reperfusion of ischemic kidneys with PMN resulted in PMN retention and potentiated ischemic injury. However, increases in PMN retention as well as decreases in GFR and TNa caused by PMN were prevented by SNP and worsened by L-NNA. Moreover, in nonischemic kidneys, activated PMN caused renal injury and PMN retention, which were prevented by SNP and worsened by L-NNA. In conclusion, 1) NO worsens ischemic injury in the absence of PMN, and 2) NO prevents the PMN component of ischemic renal injury by blocking PMN retention and the deleterious effects of activated PMN on glomerular and tubular function.
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PMID:Nitric oxide prevents neutrophil-mediated acute renal failure. 903 48

During cardiac surgery, ischemia-reperfusion injury (IRI) is thought to be a major factor in intraoperative myocardial damage. Coronary endothelial cells have been thought to play an important role in the pathogenesis of cardiac IRI. Release of nitric oxide (NO) from coronary endothelial cells is impaired following myocardial ischemia, and this may contribute to the vulnerability of the coronary circulation to thrombus-formation and vasospasm. Several experimental studies have found that NO has a cardioprotective effect in myocardial IRI. In this regard, attempts have been made to supplement NO production exogenously during reperfusion, when endogenous NO release from endothelial cells may be diminished. In a blood-reperfused heart model, L-arginine acts cardioprotectively via 2 primary possible mechanisms: (1) by blocking both neutrophil aggregation and neutrophil adherence, and (2) by scavenging oxygen-derived free-radicals. On the other hand, in a non-blood reperfused heart model, the optimal concentration of L-arginine may be low and protection may be due to 2 additional mechanisms: (3) direct coronary vasodilatation and (4) reduced oxygen demand due to vasodilatation-induced hypotension. Other studies have suggested that NO exacerbates IRI and that NO synthase (NOS) inhibitors act cardioprotectively. It has also been suggested that the pharmacological effectiveness of inhibiting NO production may be due to the prevention of peroxinitrite formation from NO and superoxide during reperfusion. This review summarizes the current understanding of the role of NO in IRI.
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PMID:The role of nitric oxide in cardiac ischemia-reperfusion injury. 907 Sep 67

Reperfusion after ischemia induces cytokines, chemoattractant chemokines, adhesion molecules, and nitric oxide (NO). The resultant neutrophil adherence and NO potentiates renal injury. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent anti-inflammatory agent that inhibits neutrophil migration and production of neutrophil chemokines and NO. Since neutrophils and NO promote renal ischemic injury, we sought to determine if alpha-MSH inhibits renal injury in a model of bilateral renal ischemia. alpha-MSH significantly reduced ischemia-induced renal damage, measured by changes in renal histology and plasma blood urea nitrogen and creatinine in mice. alpha-MSH significantly decreased tubule necrosis, neutrophil plugging, and capillary congestion. Delay of alpha-MSH treatment for 6 h after ischemia also significantly inhibited renal damage. alpha-MSH also significantly inhibited ischemic damage in rats. To begin to determine the mechanism of action of alpha-MSH, we measured its effects on mediators of neutrophil trafficking and induction of the inducible isoform of NO synthase-II. alpha-MSH inhibited ischemia-induced increases in mRNA for the murine neutrophil chemokine KC/IL-8. alpha-MSH also inhibited induction of mRNA for the adhesion molecule ICAM-1, which is known to be critical in renal ischemic injury. alpha-MSH inhibited nitration of kidney proteins and induction of NO synthase-II. We conclude: (a) alpha-MSH protects against renal ischemia/reperfusion injury; and (b) it may act, in part, by inhibiting the maladaptive activation of genes that cause neutrophil activation and adhesion, and induction of NO synthase.
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PMID:Alpha-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats. 907 23

The stimulation of NMDA receptor activates NO dependent cGMP biosynthesis with dynamic and extent different for hippocampus and brain cortex. The significantly higher NO mediated cGMP level was observed in hippocampus than in brain cortex. NMDA receptor stimulation increases NO mediated cGMP formation about 8 fold in hippocampus and 2.5 fold in brain cortex as compared to basal value (2 mM CaCl2). The activity of NO synthase and the basal level of cGMP in unstimulated slices were only slightly higher in hippocampus then in brain cortex. The CA2+ calmodulin dependent NO synthase was found in brain membrane and cytosol fraction. The enzyme activity was not affected by glucocorticoids, even after 20 days of hydrocortisone treatment in a dose of 40 mg/kg b.w. Brain ischemia induced by ligation of both common carotid arteries in gerbils increases significantly NOS activities as well as the level of cGMP and putrescine but decreases mono-ADP-ribosylation of brain proteins during reperfusion period. The ischemia evoked changes of NOS/cGMP were eliminated by specific inhibitor of neuronal form of NOS, 7-Nitrodazole (7NI) administered in a dose of 25 mg/kg b.w. 5 min. before ischemia. This inhibitor has no effect on the level of putrescine enhanced during ischemia and also biphasically during reperfusion. The inhibitor of guanylate cyclase, LY 83583 administered in a dose of 6 mg/kg b.w. 5 min before ischemia diminishes not only the enhanced level of cGMP but also NOS activity stimulated by ischemia. These results indicate that activation of NMDA receptor stimulates more significantly NO/cGMP production in hippocampus than in brain cortex suggesting the role of NO in neuronal form of NOS and inhibitor of guanylate cyclase protect the brain against excessive production of nitric oxide and cGMP during ischemia-reperfusion. These compounds may offer a new strategy in the therapy of brain ischemia.
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PMID:NMDA receptor mediated nitric oxide dependent cGMP synthesis in brain cortex and hippocampus. Effect of ischemia on NO related biochemical processes during reperfusion. 910 Feb 45

The effects of local periarterial placement of capsaicin upon pancreatic blood flow, oxygen extraction from pancreatic circulation and oxygen consumption by pancreatic tissue were measured in anesthetized dogs. These studies explored also the possible role of endogenous nitric oxide (NO) in the pancreatic vascular and metabolic responses to periarterial capsaicin. In anesthetized dogs, superior pancreatico-doudenal artery blood flow (SPBF) was measured with an ultrasonic blood flowmeter. Microcirculatory pancreatic blood flow (PBF) was measured with laser-Doppler flowmeter. Arteriovenous oxygen difference (AVO2) across the pancreatic circulation was determined spectrophotometrically. Pancreatic oxygen uptake was calculated as the product of AVO2 and SPBF. Capsaicin applied periarterialy induced initial increase in SPBF, PBF and oxygen uptake. The acute capsaicin-induced vascular dilation was followed by steady state response characterized by significant decrease in SPBF, PBF and oxygen uptake. Inhibition of NO synthase by N omega-nitro-L-arginine (L-NNA) induced pancreatic ischemia and hypoxia. After pretreatment with L-NNA the acute capsaicin-induced pancreatic vascular dilation and the increase in pancreatic oxygen uptake were significantly reduced. Above circulatory and metabolic effects of L-NNA were significantly attenuated when administration of L-NNA was combined with L-arginine. The results of these studies indicate that sensory C-fibers at rest and when activated play a role in the control of pancreatic blood flow and tissue oxygenation. These findings support also the hypothesis that NO plays a role in the mediation of pancreatic vasodilatory action of neuropeptides released from sensory C-fibers.
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PMID:Role of nitric oxide in the pancreatic vascular and metabolic responses associated with activation of capsaicin-sensitive neurons. 911 27

Nitric oxide (NO), identified as a mediator of endothelium-dependent relaxation of vascular smooth muscle, is known to cause a number of inflammatory diseases, especially ischemia-reperfusion injury. This experimental study, using a rabbit epigastric island flap, was designed to investigate whether skin flap ischemia followed by reperfusion influences serum NO concentrations. In addition, the author investigated the effects of NO synthase inhibitors and heparin on skin flap ischemia. Serum NO concentrations after 15, 30, 45, and 60 minutes of ischemia followed by reperfusion were significantly increased compared with non-ischemic controls and elevated flaps. On the other hand, serum NO concentrations were suppressed in nitro-amino-methyl-L-arginine- and aminoguanidine-treated animals. Furthermore, administration of heparin increased serum NO concentrations in controls and animals with elevated flaps, but decreased serum NO concentrations in ischemic flaps with subsequent reperfusion. These results suggest that NO is one of the factors responsible for ischemia-reperfusion injury and that NO synthase inhibitors and heparin may protect against such injury.
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PMID:The influence of skin flap ischemia on serum nitric oxide concentrations. 914 Sep 51

Nitric oxide formed in vivo in the rat brain regions of hippocampus, striatum, neocortex and cerebellum was spin trapped and measured ex vivo by cryogenic electron paramagnetic resonance spectroscopy. In non-ischemic control animals the rate of nitric oxide (NO) formation in the individual brain regions ranged from 15 to 42 pmol.g-1.min-1. During exposure to global ischemia for 7 min the generation of NO increased in all parts of the brain. In the hippocampus the rate of NO formation during ischemia increased by 6-fold from a control rate of 19 pmol.g-1.min-1. This increase was attenuated 47% by pretreatment with the NO synthase antagonist 7-nitroindazole, whereas pretreatment with the non-NMDA receptor anatogonist NBQX and the Ca2+ channel blocker NS638 did not influence the NO formation. The data show that short-duration ischemia elicits a significant, NO-synthase-dependent formation of NO in all brain regions.
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PMID:Regional measurements of NO formed in vivo during brain ischemia. 915 Aug 12

The role of endothelin and its relationship with nitric oxide (NO) production in ischemia-reperfusion associated with pancreas transplantation has been explored. For this purpose, pancreatic levels of endothelin were evaluated in an experimental model of pancreas transplantation after different periods of cold preservation. The effects of NO synthase inhibition were also evaluated. Results show posttransplantation increases in lipase and endothelin production. The release of lipase and endothelin was only prevented by NG-nitro-L-arginine methyl ester after a short ischemic period. Thus, endothelin synthesis could be a consequence of stimulation with NO in the ischemia-reperfusion associated with pancreas transplantation.
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PMID:Nitric oxide enhances endothelin production in pancreas transplantation. 916 83

During the postischemic flow response (PFR), vasodilator mediators such as nitric oxide (NO) and histamine are liberated, influencing the blood flow rate at the onset of reperfusion. The possible roles of these two mediators, and the relationship between their release, were examined during segmental intestinal ischemia of different durations and subsequent reperfusion in two series of anesthetized dogs. In series I (untreated ischemia), 15, 30, 60, and 120 min ischemia and 2 h reperfusion were studied. In series II, the same experimental protocol was repeated after pretreatment with the NO synthase inhibitor N-nitro-L-arginine (NNA, 10 mumol/kg, i.e., 2.19 mg/kg). Intramucosal pH (pHi), segmental blood flow and effluent histamine levels were measured, and segmental vascular resistance (SVR) and PFR volumes were calculated. The ischemic periods caused a considerable fall in pHi. Reperfusion resulted in an early return to normal pHi levels following a 15 or 30 min ischemia, but this process took longer after longer occlusions. In the later phase of reperfusion, SVR was elevated. The PFR volume increased in proportion to the duration of occlusion, except after the 120 min ischemia. At the onset of reperfusion, peak histamine levels rose in parallel with the duration of ischemia. During reperfusion, a prolonged decrease in pHi, an increase in SVR, and a reduction in PFR volume, with no significant histamine level elevation, were observed in the NNA-treated groups. This study indicates that both NO and histamine take part in the PFR in the canine small intestine. Inhibition of NO synthesis prevents the postischemic release of histamine.
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PMID:Possible relationship between histamine and nitric oxide release in the postischemic flow response following mesenteric ischemia of different durations. 916 74

Repetitive spreading depression (SD) waves, involving depolarization of neurons and astrocytes and up-regulation of glucose consumption, is thought to lower the threshold of neuronal death during and immediately after ischemia. Using rat models for SD and focal ischemia we investigated the expression of cyclooxygenase-1 (COX-1), the constitutive form, and cyclooxygenase-2 (COX-2), the inducible form of a key enzyme in prostaglandin biosynthesis and the target enzymes for nonsteroidal anti-inflammatory drugs. Whereas COX-1 mRNA levels were undetectable and uninducible, COX-2 mRNA and protein levels were rapidly increased in the cortex, especially in layers 2 and 3 after SD and transient focal ischemia. The cortical induction was reduced by MK-801, an N-methyl-D-aspartic acid-receptor antagonist, and by dexamethasone and quinacrine, phospholipase A2 (PLA2) inhibiting compounds. MK-801 acted by blocking SD whereas treatment with PLA2 inhibitors preserved the wave propagation. NBQX, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate-receptor antagonist, did not affect the SD-induced COX-2 expression, whereas COX-inhibitors indomethacin and diclofenac, as well as a NO synthase-inhibitor, NG-nitro-L-arginine methyl ester, tended to enhance the COX-2 mRNA expression. In addition, ischemia induced COX-2 expression in the hippocampal and perifocal striatal neurons and in endothelial cells. Thus, COX-2 is transiently induced after SD and focal ischemia by activation of N-methyl-D-aspartic acid-receptors and PLA2, most prominently in cortical neurons that are at a high risk to die after focal brain ischemia.
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PMID:Spreading depression and focal brain ischemia induce cyclooxygenase-2 in cortical neurons through N-methyl-D-aspartic acid-receptors and phospholipase A2. 917 47


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