nitroarginine and Acute-Kidney-Injury

Possible involvement of nitric oxide (NO) in the protective effect of ischemic preconditioning against the ischemia/reperfusion-induced acute renal failure was investigated. Ischemic preconditioning, which consists of three cycles of 2-minute ischemia followed by 5-minute reperfusion, was performed prior to 45-minute ischemia. Ischemic preconditioning significantly improved the renal dysfunction induced by 45-minute ischemia followed by 24-hour reperfusion. Histopathological examination of the kidney of ischemia/reperfusion rats revealed severe renal damage, and suppression of the damage was seen with the ischemic preconditioning treatment. NO metabolites (NOx) production in the kidney after 45-minute ischemia and reperfusion was markedly increased in ischemia/reperfusion rats with ischemic preconditioning, compared with animals not subjected to ischemic preconditioning, and these increases correlated with changes in endothelial NO synthase (eNOS) protein expression in renal tissues. The improvement of renal dysfunction in ischemic preconditioning rats was abolished by the pretreatment with NG-nitro-L-arginine, a nonselective NOS inhibitor, but not with aminoguanidine, an inducible NOS inhibitor. In addition, increment of endothelin-1 (ET-1) content in the kidney after the reperfusion was markedly suppressed by ischemic preconditioning treatment. These findings suggest that the protective effect of ischemic preconditioning on ischemia/reperfusion -induced acute renal failure is closely related to the renal nitric oxide production following the increase in eNOS expression after the reperfusion and that the suppressive effect of ischemic preconditioning on the ischemia/reperfusion -induced renal ET-1 overproduction may be partly involved in the ameliorating effect of ischemic preconditioning.

Topics: Acute Kidney Injury; Animals; Blood Urea Nitrogen; Endothelin-1; Enzyme Inhibitors; Guanidines; Ischemic Preconditioning; Kidney; Male; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Rats; Rats, Sprague-Dawley

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.

Topics: Absorption; Acute Kidney Injury; Animals; Arginine; Enzyme Inhibitors; Glomerular Filtration Rate; Ischemia; Kidney; Neutrophils; Nitric Oxide; Nitroarginine; Nitroprusside; Rats; Reference Values; Renal Circulation; Reperfusion Injury; Sodium

Changes in nitric oxide (NO) levels were determined in ischaemic acute renal failure in streptozotocin-induced diabetes mellitus rats. Two weeks after streptozotocin administration and immediately after right nephrectomy, the left renal artery was occluded for 60 min. Similar procedures were carried out in non-diabetic rats. The nitrite (NO2) + nitrate (NO3) levels were measured in plasma and urine. The effects of chronic oral supplementation with L-arginine and an NO synthase inhibitor (N-omega-nitro-L-arginine) were also studied in both diabetic and non-diabetic rats before and after renal artery clamping. The rats with diabetic acute renal failure had a much lower creatinine clearance (90 +/- 22 microliters.min-1. 100g body weight-1, p < 0.005), and higher fractional excretion of sodium (FENa)% (10.90 +/- 4.2, p < 0.001) and protein excretion (2078 +/- 69 micrograms/ml creatinine clearance, p < 0.001) compared with the respective values in the non-diabetic groups (163 +/- 30; 1.46 +/- 86; 453.3 +/- 31). The plasma and urine NO2 + NO3 levels were significantly higher in the untreated diabetic rats compared with the untreated normal rats before ischaemia (p < 0.001). The ischaemic acute renal failure in non-diabetic rats increased the plasma and urinary NO2 + NO3 excretion after ischaemia. The urinary excretion of these metabolites decreased significantly and their plasma levels remained unchanged in the ischaemic diabetic rats. The L-arginine administration resulted in a small but significantly higher creatinine clearance after clamping in the non-diabetic rats. The NO synthase inhibitor caused deterioration in renal function in all ischaemic and non-ischaemic groups. In summary, the greater vulnerability to ischaemia of the diabetic kidney seems to be associated with both impaired response to and impaired production of NO.

Topics: Acute Kidney Injury; Analysis of Variance; Animals; Arginine; Creatinine; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Ischemia; Nephrectomy; Nitrates; Nitric Oxide; Nitrites; Nitroarginine; Rats; Rats, Wistar; Reference Values; Renal Artery; Renal Circulation; Sodium

EDRF results from the metabolism of L-arginine. N-omega-nitro-L-arginine is a nitric oxide synthase inhibitor (L-arginine competitive inhibitor). Acute renal failure was induced by i.m glycerol (50%) 5 ml/kg bw. L-arginine: 3 mg/kg bw/min for 60 min before and 60 min after glycerol administration. L-arginine inhibitor (150 micrograms/kg bw/min for 120 min). Cin, Cpah and FENa% were measured immediately or 24 h after glycerol (mean of three periods of 20 min). A second series of similar experiments was done in dehydrated (16 h) rats with a high dose of glycerol (50% solution, 10 ml/kg bw). L-arginine ameliorates the severity of ARF immediately after glycerol administration and enhances the recovery of glycerol-induced ARF. The L-arginine inhibitor resulted in a more severe ARF. Urinary cGMP decreased significantly after glycerol administration. It is concluded that nitric oxide has an important pathogenetic role in the glycerol induced ARF.

Topics: Acute Kidney Injury; Amino Acid Oxidoreductases; Animals; Arginine; Blood Pressure; Cyclic GMP; Female; Glomerular Filtration Rate; Glycerol; Male; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Rats; Rats, Sprague-Dawley; Renal Circulation

This study was undertaken to examine the possible role of endothelium-derived relaxing factor (EDRF), identified as nitric oxide (NO), in the pathogenesis of radiocontrast-induced acute renal failure in rats. Normal and salt-depleted rats were monitored for 60 min or 24 h after radiocontrast administration. The administration of L-arginine to normal rats abolished the immediate decrease in p-aminohippurate clearance (CPAH) and attenuated the decrease in inulin clearance (CIn). The administration of NO synthase inhibitor to the salt-depleted animals resulted in a significantly more pronounced decrease in CPAH compared with both the control and the L-arginine-treated animals. The recovery of CIn 24 h after radiocontrast administration to the salt-depleted rats was significantly better in the L-arginine-treated rats than in either the control or inhibitor-treated groups. The administration of radiocontrast material resulted in a significant decrease in urinary guanosine 3',5'-cyclic monophosphate as well as NO2 + NO3 excretion. This decrease was significantly attenuated by L-arginine. Our results 1) suggest that NO plays a major role in the pathogenesis of radiocontrast-induced acute renal failure and 2) suggest a novel therapeutic approach, i.e., the use of L-arginine in this form of acute renal failure.

Topics: Acute Kidney Injury; Animals; Arginine; Blood Pressure; Cyclic GMP; Diatrizoate; Female; Nitrates; Nitric Oxide; Nitrites; Nitroarginine; Rats; Rats, Sprague-Dawley; Sodium; Time Factors

Acute renal failure in rats was induced by transient occlusion of bilateral renal arteries and veins to investigate whether insulin-like growth factor-I (IGF-I) has an effect on the damaged renal function or not. Administration of IGF-I at 0.01, 0.1 and 1 mg/kg by s.c. injection caused a 18.7, 33.0 and 66.5% increase of glomerular filtration rate and 54.8, 61.2 and 84.1% decrease of blood urea nitrogen, respectively, compared with the values in the saline-treated group 2 days after ischemia. Other renal parameters tested such as fractional excretion of sodium, N-acetyl-beta-D-glucosaminidase and tubular reabsorptance of phosphorus which are thought to represent renal function of proximal and distal tubules, respectively, were also improved by IGF-I treatment. A histochemical study also supported these observations. Severe epithelial necrosis of proximal tubules and decrease of brush borders were observed 2 days after transient ischemia in the saline-treated group, whereas marked histochemical alterations were not observed in the IGF-I-treated group. L-NG-nitroarginine, an inhibitor of nitric oxide synthetase, prevented the improvement of glomerular filtration rate and blood urea nitrogen by IGF-I at 1 mg/kg, suggesting that the ameliorative action on renal function by IGF-I is mediated via nitric oxide, possibly its vasodilating action. These findings provide the first evidence for the efficacy of IGF-I in the model of acute renal failure, suggesting that IGF-I may be useful for the treatment of acute renal failure.

Topics: Acute Kidney Injury; Animals; Arginine; Blood Urea Nitrogen; Drug Synergism; Glomerular Filtration Rate; Insulin-Like Growth Factor I; Ischemia; Kidney; Male; Nitric Oxide; Nitroarginine; Rats; Rats, Sprague-Dawley; Renal Artery; Renal Veins