Role of endothelium-related mechanisms in the pathophysiology of renal ischemia/reperfusion in normal rabbits.
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.
Caramelo
C
C
Laboratorio de Nefrología e Hipertensión, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
Espinosa
G
G
Manzarbeitia
F
F
Cernadas
M R
MR
Pérez Tejerizo
G
G
Tan
D
D
Mosquera
J R
JR
Digiuni
E
E
Montón
M
M
Millás
I
I
Hernando
L
L
Casado
S
S
López-Farré
A
A
D000818:Animals; D001120:Arginine / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D006439:Hemodynamics; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology; D009573:Nitrites / Q000652:urine; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D012016:Reference Values; D012079:Renal Circulation; D015424:Reperfusion; D013997:Time Factors; D014664:Vasodilation / Q000502:physiology
D009573:Nitrites; D009569:Nitric Oxide; D001120:Arginine; D009195:Peroxidase