Protective effect of N-acetyl-L-cysteine on the renal failure induced by inferior vena cava occlusion.
BACKGROUND
Renal ischemia is produced during orthotopic liver transplantation when the inferior vena cava is clamped above the renal veins (inferior vena cava occlusion [IVCO]), and it often leads to postoperative renal failure. Although free radicals and nitric oxide (NO) have been implicated in the pathogenesis of ischemic renal failure, the effect of free radical scavengers in this model is unknown.


METHODS
The effects of N-acetyl-L-cysteine (NAC), a free radical scavenger, on the acute renal failure that follows IVCO were evaluated in pentobarbital-anesthetized dogs. The effect of NO synthesis inhibition with NG-nitro-L-arginine methyl ester (NAME) was also studied. Renal vascular endothelial function was tested by infusing acetylcholine (Ach) into the renal artery before the ischemia and during reperfusion.


RESULTS
Renal failure developed during IVCO and persisted during reperfusion in all groups. However, in NAC-pretreated dogs, the glomerular filtration rate recovered progressively, reaching 31% of basal preischemic values 150 min after reperfusion. During reperfusion, fractional excretion of sodium increased above preischemic values only in the control group, which indicates a beneficial effect of NAC and NAME on the tubular dysfunction observed during reperfusion. The renal response to Ach was abolished in control dogs and in animals given NAME during reperfusion, which indicates endothelial dysfunction. However, in NAC-pretreated dogs, the renal response to Ach was preserved during reperfusion.


CONCLUSIONS
These results demonstrate that NAC ameliorates the renal failure and renal endothelial dysfunction induced by IVCO. This protective effect was abolished by NAME, which suggests that NO is involved in the beneficial effects of NAC. These data also suggest that the use of NAC could be beneficial in ameliorating the acute renal failure observed after orthotopic liver transplantation.
Salom
M G
MG
Departamento de Fisiología y Farmacología, Facultad de Medicina, Murcia, Spain. mgsalom@fcu.um.es
Ramírez
P
P
Carbonell
L F
LF
López Conesa
E
E
Cartagena
J
J
Quesada
T
T
Parrilla
P
P
Fenoy
F J
FJ
D000109:Acetylcholine / Q000494:pharmacology; D000111:Acetylcysteine / Q000494:pharmacology*; D058186:Acute Kidney Injury / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D003250:Constriction; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007269:Injections, Intra-Arterial; D007511:Ischemia / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D012079:Renal Circulation / Q000502:physiology; D015424:Reperfusion; D014682:Vena Cava, Inferior / Q000503:physiopathology*
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine