Role of Endothelium-Related Mechanisms in the Pathophysiology of Renal Ischemia/Reperfusion in Normal Rabbits

Abstract

The present study addressed the effect of interventions aimed to increase NO in the setting of acute renal ischemia/reperfusion (I/R) in uninephrectomized rabbits. In the 60-minute post-I/R period, L-arginine+superoxide (O2.-) dismutase (SOD) synergistically improved the renal functional (69.4% versus 10.4% of the pre-I/R glomerular filtration rate with or without L-arginine+SOD, respectively; p < .01) and histological parameters (82.9% decrease of medullary congestion in L-arginine+SOD, P < .01 versus vehicle) and blocked the I/R-dependent neutrophil accumulation (89.3% reduction). In spite of these results over the short term, a second set of experiments disclosed that the protection by L-arginine+SOD was no longer present at 24 and 48 hours (plasma creatinine in vehicle-treated versus L-arginine+SOD-treated animals [mg/100 mL]: 24 hours after I/R, 9.4 +/- 1.9 versus 8.07 +/- 0.65; 48 hours after I/R, 11.6 +/- 3.6 versus 9.7 +/- 0.9; P = NS in all the cases). Additional experiments were conducted using a milder 30-minute ischemic model, which showed no significant functional or histological protection by using L-arginine+SOD. In conclusion, our experiments disclosed the following: (1) the critical importance of the interaction between NO and O2.- in the acute protective effect of L-arginine (this effect not only improved renal function and histology but also reduced neutrophil accumulation) and (2) the discordance existing between the immediate protection afforded by L-arginine+SOD and the lack of protection observed at 24 and 48 hours. This finding suggests that a punctual intervention on the NO system at the time of I/R is not sufficient to reduce renal damage over the long term.

Oligomycin, an F1FO-ATPase Inhibitor, Protects Against Ischemic Acute Kidney Injury in Male but Not in Female Rats

“…The kidneys were preserved in phosphate-buffered 10% formalin (pH 7.4), after which the kidneys were chopped into small pieces, embedded in paraffin wax, cut at 4 mm, and stained with hematoxylin and eosin. Histopathological changes were analyzed for tubular necrosis and proteinaceous casts as described by Caramelo et al (16). These lesions were graded as follows: no damage (0), mild (1: unicellular, patchy isolated damage), moderate (2: damage less than 25%), severe (3: damage between 25% and 50%), and very severe (4: more than 50% damage).…”

Preventive Effect of GGsTop, a Novel and Selective γ-Glutamyl Transpeptidase Inhibitor, on Ischemia/Reperfusion-Induced Renal Injury in Rats

“…The kidneys were then fixed in phosphate-buffered 10% formalin, pH 7.4, after which they were chopped into small pieces, embedded in paraffin wax, cut at 4 m, and stained with hematoxylin and eosin. Histopathological changes were analyzed for tubular necrosis, proteinaceous cast, and medullary congestion, as described by Caramelo et al (1996). Tubular necrosis and proteinaceous casts were graded as follows: no damage (severity score 0), mild (1, unicellular, patchy isolated damage), moderate (2, damage less than 25%), severe (3, damage between 25 and 50%), and very severe (4, more than 50% damage).…”

Effect of L-arginine on Hemodynamic, Biochemical, and Histopathological Outcomes in a New Zealand Rabbit Model of Renal Ischemia–Reperfusion Injury

“…Caramelo et al (14) administered superoxide dismutase together with L-arginine and demonstrated that there is a remarkable increase in renal functions and urine volume and that this arises from the synergistic effects of these two substances. Burra et al (15) expressed that L-arginine therapy reduces histopathological injury in pigs that have been exposed to renal I/R.…”