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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the pase decade, several experimental models of acute renal failure (ARF) have been evaluated with micropuncture and hemodynamic techniques. Five of these models have been most extensively studied: glycerol injection, renal artery clamping, intrarenal norepinephrine infusion, uranyl nitrate, and mercuric chloride administration. In the first three models, renal ischemia is the initiating insult, whereas in the two nephrotoxic models a direct effect of the agent on cellular integrity is also seemingly operative. In all of these models, renal blood flow 24--48 h after the initial insult either spontaneously returns to normal or can be elevated to this level with volume expansion but without restoration of the glomerular filtration rate. Therefore, the maintenance of ARF in these various models is due to other factors, which include tubular obstruction, leakage of filtrate across damaged tubular epithelium, and a decrease in the glomerular capillary ultrafiltration coefficient. In a given model, one or all three of these alterations may be present. Although these various models may not be completely analogous to the clinical setting, they have provided powerful tools for the study of ARF and their use has greatly increased our knowledge in this field.
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PMID:Current concepts on the pathophysiology of acute renal failure. 34 2

We evaluated, in renal epithelial cells with a proximal tubule phenotype, the effect of nitric oxide (NO) on ecto-5 -nucleotidase (5'-N U), the underlying mechanism and its functional consequence. Sodium nitroprusside (SNP, 1-1000 microM), a NO donor, inhibited 5'-NU activity in a time- and concentration-dependent manner. Consequently, NO blunted the inhibition by extracellular cyclic AMP (cAMP, 10-1000 microM) of sodium-phosphate cotransport, a pathway which involves degradation of adenosine monophosphate (AMP) by 5'-NU. SNP-induced inhibition of 5'-NU was not mediated by cyclic GMP, since it was not mimicked by atrial natriuretic peptide, and was reproduced by isosorbide dinitrate and sodium nitrate, two NO donors. SNP and genuine NO decreased the activity of 5'-NU in renal homogenates, and the effect of SNP was potentiated by dithiothreitol and glutathione, but not by nicotinamide adenine dinucleotide. In vivo in rats, kidney ischemia/reperfusion, which activates inducible NO-synthase, inhibited renal 5'-NU. This inhibition was prevented by Nomega-nitro-L-arginine methyl ester, a NO-synthase inhibitor. These results indicate that: (i) NO-related activity inhibited the activity of an ecto-enzyme, 5'-NU, most likely through S-nitrosylation of the enzyme; (ii) inhibition of 5'-NU activity by NOx, which can occur in vivo under pathophysiological conditions, affected the extent to which extracellular cAMP inhibited sodium-Pi cotransport.
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PMID:Inhibition of ecto-5'-nucleotidase by nitric oxide donors. Implications in renal epithelial cells. 861 29

Renal ischemia/reperfusion (I/R) injury results in decreased glomerular filtration and renal blood flow (RBF) and increased urine output, characterized by natriuresis and impaired concentrating ability. We studied unilateral I/R in rats to assess renal handling of nitric oxide (NO). Prior to I/ R, we measured urine flow rate (V), inulin clearance (C[IN]), para-aminohippuric acid clearance (C[PAH]), NO clearance (C[NOx] determined from metabolites NO2 and NO3), tubular transport of NOx (T[NOx], filtered load +/- urinary excretion), urine sodium and potassium excretion (U[Na]V, U[K]V), fractional excretion of sodium (FENa), and fractional excretion of NOx (FENOx) in each kidney. The left renal artery was then ligated for 30 min, followed by 30 min of reperfusion, and all measurements were repeated. C(IN) and C(PAH) were decreased in I/R kidneys compared with the contralateral kidney or pre-ischemia controls. V, FENa, and U(K)V were all significantly increased in I/R kidneys. Plasma NOx concentration was lower after injury in all animals (23.3 +/- 2.8 post injury vs. 30.4 +/- 7.7 microM pre injury, P < 0.05). C(NOx) was significantly higher in I/R kidneys (0.14 +/- 0.05 ml/min per g kidney weight) than in pre-injury kidneys (0.03 +/- 0.02 right, 0.04 +/- 0.30 left) or the contralateral controls (0.04 +/- 0.02) (P < 0.05 for all three controls). T(NOx) showed net tubular reabsorption of NOx in all kidneys (11 +/- 6 in post-ischemic left kidneys vs. 25 +/- 20 in left pre-ischemia, 33 +/- 13 in right pre-ischemia, and 21 +/- 4 right post-ischemia, nM/min per g kidney weight, P = NS). FENOx was higher in injured kidneys (28% +/- 18) than in pre-injury (3% +/- 0.6, 5% +/- 3) or contralateral controls (6% +/- 3) (P < 0.05 for all three controls). Renal NOx excretion and clearance are increased despite decreased plasma levels of NO metabolites after I/R injury. This increased excretion is not dependent on RBF or glomerular filtration, but may be related to impaired tubular reabsorption of NOx combined with increased intra-renal NO production.
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PMID:Nitric oxide metabolism following unilateral renal ischemia/reperfusion injury in rats. 950 63

Tissue subjected to a period of ischemia undergoes functional and morphological damage that increases during the reperfusion phase. In this study, the protective effect of aprotinin, which is a protease inhibitor, was assessed in a rabbit unilateral renal ischemia-reperfusion (I/R) model. New Zealand rabbits, weighing 1.5-2 kg, were randomized to receive either aprotinin 30.000 KIU x kg(-1) and 10.000 KIU x kg(-1) x h(-1) i.v. infusion (group I, n= 7) or equivalent volumes of 0.09% sodium chloride (SF) (group II, control, n= 7) i.v. 15 minutes before a 45 minutes interruption of left renal artery blood flow and then 45 minutes of reperfusion. Blood samples were obtained before and after the ischemia-reperfusion period for measurement of nitric oxide serum (NO) levels with the nitrite/nitrate colorimetric method. Histological changes were evaluated by quantitative measurements using a numerical score (0-4) and immunohistochemical analysis of inducible nitric oxide synthase (iNOS) expression was determined. A Wilcoxon W -test was used for statistical analysis of biochemical measurements and mean values were expressed as +/-sd. Histological examination revealed the distinctive pattern of ischemic renal tissue injury with obvious signs of epithelial necrosis. The intensity of epithelial necrosis was more extensive in the SF group. Immunohistochemical analysis showed that there was severe immunostaining in the tubular epithelium in both cortical and medullary regions and iNOS expression was more intense in SF-only cases. The staining results for aprotinin cases did not differ much from the non-ischemic kidney. Biochemical analysis revealed an increase in serum NO levels in both groups (P< 0.05), but this was more evident in the SF group (mean NO levels were 38.63 +/- 19.03 micromol x L(-1) in group I, 50.63 +/- 24.28 micromol x L(-1) in group II). No statistically important difference was observed between the two groups. These results suggest that aprotinin may be beneficial in the prevention of systemic inflammation after transient renal ischemia.
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PMID:The effect of aprotinin on ischemia-reperfusion injury in the rabbit kidney. 1173 50

Since hepatorenal syndrome is a functional renal failure due to renal ischemia in cirrhotics with refractory ascites, we investigated whether increased intra-abdominal pressure (IAP) impairs the renal function and perfusion in cirrhotic portal hypertensive rats. Eight groups of 32 rats each were studied, including 4 control and 4 CCl(4) cirrhotic groups. These were subdivided into two groups each, with and without an increased IAP, and further subdivided into groups of rats with and without NO inhibition. IAP was increased to 20 mm Hg for 7 consecutive days by means of an intraperitoneally placed balloon filled with water. The animals were studied in normal conditions and after inhibition of NO synthesis. Changes in mean arterial pressure and renal microcirculation by means of femoral artery catheterization and laser-Doppler technique, respectively, were recorded. Venous samples for determination of plasma renin-aldosterone activity, biochemical parameters of liver and renal function, and plasma nitrite/nitrate levels as an index of NO synthesis were drawn. Cirrhotic rats showed decreased renal microcirculation (P = 0.05), while elevated IAP produced a further decrease (P = 0.01). Renin-aldosterone levels found increased (P = 0.001) in cirrhotics, and elevated IAP produced a further increase (P = 0.01] in both groups. Inhibition of NO synthesis resulted in a nonsignificant decrease in both renal microcirculation and renin-aldosterone levels in all experimental groups. Liver and renal function was found to be impaired in cirrhotics, but increased IAP had a nonsignificant further functional impairment in both organs. In conclusion, chronically elevated IAP in cirrhotic rats is associated with an increase in renin-aldosterone levels and significant impairment of renal perfusion.
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PMID:The influence of continuous seven-day elevated intra-abdominal pressure in the renal perfusion in cirrhotic rats. 1457 84

Nitric oxide (NO) is synthesized from l-arginine by nitric oxide synthase (NOS), and nitrite and nitrate are believed to be waste forms of NO. We previously reported an enzyme-independent pathway of NO generation from nitrite in acidic conditions. In this study, we show nitrite-derived NO formation in renal ischemia-reperfusion injury using electron paramagnetic resonance (EPR) spectroscopy. In this experiment, we utilized a stable isotope of [(15)N]nitrite as a source of nitrite to distinguish l-arginine-derived NO from [(15)N]nitrite-derived (15)NO. Intravenous infusion of a stable isotope of [(15)N]nitrite ((15)NO(2)(-)) facilitated the formation of Hb(15)NO during renal ischemia, which demonstrated that the origin of NO was nitrite. The EPR signal of Hb(15)NO in kidney appeared after 40 min of renal ischemia, and renal reperfusion decreased the Hb(15)NO level in the kidney and increased it in blood by contrast. In addition, the amount of HbNO was nitrite concentration dependent, and this formation was NOS independent. Our findings suggest that nitrite can be an alternative source of NO in ischemic kidney and that it binds with hemoglobin and then is spread by the circulation after reperfusion.
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PMID:Nitrite-derived nitric oxide formation following ischemia-reperfusion injury in kidney. 1536 87

The role of poly(ADP-ribose) (PAR) glycohydrolase (PARG) in the pathophysiology of renal ischemia/reperfusion (I/R) injury is not known. Poly(ADP-ribosyl)ation is rapidly stimulated in cells after DNA damage caused by the generation of reactive oxygen and nitrogen species during I/R. Continuous or excessive activation of poly(ADP-ribose) polymerase-1 produces extended chains of ADP-ribose on nuclear proteins and results in a substantial depletion of intracellular NAD(+) and subsequently, ATP, leading to cellular dysfunction and, ultimately, cell death. The key enzyme involved in polymer turnover is PARG, which possesses mainly exoglycosidase activity but can remove olig(ADP-ribose) fragments via endoglycosidic cleavage. Thus, the aim of this study was to investigate whether the absence of PARG(110) reduced the renal dysfunction, injury, and inflammation caused by I/R of the mouse kidney. Here, the renal dysfunction and injury caused by I/R (bilateral renal artery occlusion [30 min] followed by reperfusion [24 h]) in mice lacking PARG(110), the major nuclear isoform of PARG, was investigated. The following markers of renal dysfunction and injury were measured: Plasma urea, creatinine, aspartate aminotransferase, and histology. The following markers of inflammation were also measured: Myeloperoxidase activity, malondialdehyde levels, and plasma nitrite/nitrate. The degree of renal injury and dysfunction caused by I/R was significantly reduced in PARG(110)-deficient mice when compared with their wild-type littermates, and there were no differences in any of the biochemical parameters measured between sham-operated PARG(110)(-/-) mice and sham-operated wild-type littermates. Thus, it is proposed that endogenous PARG(110) plays a pivotal role in the pathophysiology of I/R injury of the kidney.
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PMID:Mice lacking the 110-kD isoform of poly(ADP-ribose) glycohydrolase are protected against renal ischemia/reperfusion injury. 1567 8

Reactive oxygen and nitrogen species play a key role in the pathophysiology of renal ischemia-reperfusion (I/R) injury. Recent studies have shown that nitrite (NO(2)(-)) serves as an endogenous source of nitric oxide (NO), particularly in the presence of hypoxia and acidosis. Nanomolar concentrations of NO(2)(-) reduce injury following I/R in the liver and heart in vivo. The purpose of this study was to evaluate the role of NO(2)(-) in renal I/R injury. Male Sprague-Dawley rats underwent a unilateral nephrectomy followed by 45 min of ischemia of the contralateral kidney or sham surgery under isoflurane anesthesia. Animals received normal saline, sodium NO(2)(-), or sodium nitrate (NO(3)(-); 1.2 nmol/g body wt ip) at 22.5 min after induction of ischemia or 15 min before ischemia. A separate set of animals received saline, NO(2)(-), or NO(3)(-) (0.12, 1.2, or 12 nmol/g body wt iv) 45 min before ischemia. Serum creatinine and blood urea nitrogen were increased following I/R injury but were not significantly different among treatment groups at 24 and 48 h after acute renal injury. Interestingly, NO(3)(-) administration appeared to worsen renal injury. Histological scoring for loss of brush border, tubular necrosis, and red blood cell extravasation showed no significant differences among the treatment groups. The results indicate that, contrary to the protective effects of NO(2)(-) in I/R injury of the liver and heart, NO(2)(-) does not provide protection in renal I/R injury and suggest a unique metabolism of NO(2)(-) in the kidney.
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PMID:Effects of sodium nitrite on ischemia-reperfusion injury in the rat kidney. 1652 23

In normal conditions, nitric oxide (NO) is oxidized to the anion nitrite, but in hypoxia, this nitrite may be reduced back to NO by the nitrite reductase action of deoxygenated hemoglobin, acidic disproportionation, or xanthine oxidoreductase (XOR). Herein, is investigated the effects of topical sodium nitrite administration in a rat model of renal ischemia/reperfusion (I/R) injury. Rats were subjected to 60 min of bilateral renal ischemia and 6 h of reperfusion in the absence or presence of sodium nitrite (30 nmol) administered topically 1 min before reperfusion. Serum creatinine, serum aspartate aminotransferase, creatinine clearance, fractional excretion of Na(+), and plasma nitrite/nitrate concentrations were measured. The nitrite-derived NO-generating capacity of renal tissue was determined under acidic and hypoxic conditions by ozone chemiluminescence in homogenates of kidneys that were subjected to sham, ischemia-only, and I/R conditions. Nitrite significantly attenuated renal dysfunction and injury, an effect that was abolished by previous treatment of rats with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide (2.5 mumol intravenously 5 min before ischemia and 50 nmol topically 6 min before reperfusion). Renal tissue homogenates produced significant amounts of NO from nitrite, an effect that was attenuated significantly by the xanthine oxidoreductase inhibitor allopurinol. Taken together, these findings demonstrate that topically administered sodium nitrite protects the rat kidney against I/R injury and dysfunction in vivo via the generation, in part, of xanthine oxidoreductase-catalyzed NO production. These observations suggest that nitrite therapy might prove beneficial in protecting kidney function and integrity during periods of I/R such as those encountered in renal transplantation.
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PMID:Nitrite-derived nitric oxide protects the rat kidney against ischemia/reperfusion injury in vivo: role for xanthine oxidoreductase. 1720 21

Nitric oxide (NO), produced by nitric oxide synthase, is implicated in the pathophysiology of renal ischemia/reperfusion (I/R) injury. This study sought to elucidate the impact of pharmacological induction of heme oxygenase-1 (HO-1) on renal I/R injury. Rats were subjected to 45 minutes of renal ischemia followed by various times of reperfusion (30 minutes, 1 hour, or 3 hours). Plasma from sacrificed rats was obtained, and the kidneys processed for the expression of iNOS, cleaved caspase-3, p38MAPK and for immunohistochemical analysis. Furthermore, we determined renal and plasma levels of lipid hydroperoxides, total thiol groups, and plasmatic NO2-/NO3- formation. Our results showed a time-dependent increase in iNOS expression, which was also confirmed by increased plasma formation of NO2-/NO3-. Interestingly, this effect was reversed by pretreatment (12 hours) with SnCl2, a potent and specific inducer of renal HO-1 expression and activity, or by intraperitoneal injection of biliverdin (10 mg/kg). Furthermore, we observed a concomitant reduction in plasma and renal LOOH formation, a normalization of renal total thiol content, a reduction of caspase-3-mediated apoptosis, and a significant increase in p38MAPK phosphoration. Taken together, these results suggested that HO-1 and its byproduct biliverdin play major roles in the pathophysiological cascade leading to renal I/R injury.
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PMID:Pharmacological induction of heme oxygenase-1 inhibits iNOS and oxidative stress in renal ischemia-reperfusion injury. 1808 6


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