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 relative importance of endothelial derived relaxing factor (EDRF)/nitric oxide (NO) in maintaining kidney function in normal condition and in acute renal failure (ARF) were evaluated in inactin anesthetized rats. ARF was induced by unilateral occlusion of the left renal artery (40 min) followed by reperfusion, with the contralateral kidney serving as normal control. This protocol resulted in marked reductions in renal plasma flow (RPF), glomerular filtration rate (GFR) and increases in fractional sodium excretion (FENa) and urinary protein excretion in the post-ischemic kidney in comparison to the contralateral normal kidney. Administration of the nitric oxide (NO) synthase inhibitor NG--monomethyl-L-arginine (0.25 mg/kg per min, L-NMMA) exacerbated the ischemia-induced changes in renal functions as reflected by further reductions in urine flow (V), GFR, marked sodium wasting and renal edema. Pretreatment of the animals with NO precursor L-arginine (2.5 mg/kg per min, L-Arg) abolished the detrimental effects of L-NMMA in ARF. In contrast, D-Arginine (2.5 mg/kg per min, D-Arg) failed to reverse the detrimental effects of L-NMMA. Infusion of L-Arg alone also resulted in improvements in RPF and GFR in the ischemic kidney. The results of the present study suggest that the function of the ischemic kidney is sustained by EDRF/NO and is thus more sensitive to NO synthase inhibition.
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PMID:Inhibition of endothelial derived relaxing factor (EDRF) aggravates ischemic acute renal failure in anesthetized rats. 823 7

1. The aims of the present study were to detect changes in superoxide anion (O2.-), nitric oxide (NO) and other reactive oxygen species (ROS) directly by measurement of chemiluminescence (CL) and to investigate the role of L-arginine, a nitric oxide synthase (NOS) substrate, and NG-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, together with their molecular enantiomers D-arginine and D-NAME, in a rat mesenteric ischaemia-reperfusion (I/R) model. 2. Seventy-nine female Wistar albino rats were divided into eight groups. The first three groups underwent sham operation; group 1 was the control group, group 2 received L-arginine and group 3 received L-NAME. Ischaemia was produced in the remaining five groups by ligation of the superior mesenteric artery for 30 min followed by 60 min reperfusion. Group 4 rats were control I/R rats and groups 5-8 received either L-arginine, L-NAME, D-arginine or D-NAME, respectively. 3. Both luminol and lucigenin CL was significantly increased in I/R groups compared with sham-operated groups. L-Arginine significantly reduced CL measurements. D-Arginine was also protective, but not as much as L-arginine. Both L- and D-arginine had in vitro O2.- (-)scavenging potential, as tested by the xanthine-xanthine oxidase system. NG-Nitro-L-arginine methyl ester decreased lipid peroxidation values in addition to reducing CL measurements. Nitric oxide concentrations were significantly increased in I/R groups in comparison with sham-operated groups. Peroxynitrite formation was increased by I/R. Treatment with L-NAME was beneficial by reducing NO concentrations in the reperfused ileum. 4. In our I/R model, O2.-, NO and other ROS were increased. Although NOS inhibitors were effective in reducing oxidative damage, increasing NO concentrations with L-arginine was also beneficial, presumably due to the ability of L-arginine to inhibit phagocyte adherence and its radical scavenging potential. In fact, NO may have different effects in terms of tissue injury or protection depending on the concentration of oxygen and the haemodynamic state of the tissue.
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PMID:Oxygen radicals and nitric oxide in rat mesenteric ischaemia-reperfusion: modulation by L-arginine and NG-nitro-L-arginine methyl ester. 980 62

The role of the L-arginine/nitric oxide (NO) pathway in myocardial ischaemic/reperfusion injury remains controversial in experimental animal models. The aim of the present studies was to investigate the role of this pathway in the human myocardium. Myocardial specimens from right atrial appendages of patients undergoing elective coronary bypass graft surgery were incubated in crystalloid buffer at 37 degrees C and subjected to 120 min of simulated ischaemia followed by 120 min of reoxygenation. Tested drugs were added 15 min before ischaemia, and maintained during ischaemia and throughout reoxygenation. Ischaemia resulted in severe myocardial damage, as assessed by the leakage of lactate dehydrogenase (LDH) into the incubation medium and by the capacity of the tissue to reduce 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to formazan product. L-Arginine (10 mM), a precursor of NO, significantly decreased LDH leakage (from 9.0+/-0.6 to 5.3+/-0.3 units/g wet wt; P<0.05), but had no effect on MTT reduction or oxygen consumption. D-Arginine (10 mM), N(G)-nitro-L-arginine methyl ester (L-NAME; 0.5 mM), an NO synthase inhibitor, and S-nitroso-N-acetylpenicillamine (at 1, 100, 500 and 1000 microM), an NO donor, had no significant effects on the measured indices, and L-NAME did not reverse the protection afforded by L-arginine against LDH leakage. In addition, the formation of nitrotyrosine was not influenced by ischaemia/reoxygenation alone or by the agents investigated. In conclusion, these data suggest that L-arginine affords modest protection against ischaemic/reoxygenation injury of the human myocardium, an action that is NO-independent, and that NO metabolism does not play a significant role in this model.
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PMID:Role of the L-arginine/nitric oxide pathway in ischaemic/reoxygenation injury of the human myocardium. 1109 92