L-Arginine does not affect renal morphology and cell survival in ischemic acute renal failure in rats.
BACKGROUND
L-Arginine (L-Arg), a substrate of nitric oxide synthases, improves renal function in ischemic acute renal failure (iARF). We evaluated whether L-Arg improves renal morphology and cell survival in the course of iARF.


RESULTS
iARF was induced in rats by bilateral clamping of renal arteries for 45 min. L-Arg was applied intraperitoneally during clamping, and orally during 14 days of follow-up. Morphology and cell survival of renal cortical and medullar tissue was analyzed on days 1, 3, 7, and 14 of follow-up, using toluidine blue staining and immunohistochemistry of perfusion-fixated tissue, and Western blot analysis of tissue homogenate. Renal tubular injury showed typical features of necrosis and was most severe on days 1 and 3 after clamping, predominantly in S3 segments, with almost complete recovery by day 14. Enhanced medullar monocyte infiltration, determined by ED-1 expression as well as by immunohistochemistry, and enhanced expression of proliferating cell nuclear antigen (PCNA), indicative of proliferation and regeneration, accompanied these morphological changes. Compared to controls, L-Arg had no impact on renal morphology, ED-1, and PCNA expression. Furthermore, expression of markers of apoptosis Bcl-2, Bax, and cleaved caspase-3 was only slightly increased in iARF rats, compared to sham-operated animals, and was also not influenced by L-Arg.


CONCLUSIONS
Despite its repeatedly reported positive impact on renal function as also shown in our model, L-Arg does not alter cell death and proliferation in the course of iARF in our model. Thus, different mechanisms have to be considered, in particular improved intrarenal hemodynamics.
Division of Nephrology, Department of Medicine, Julius Maximilian University, Würzburg, Germany.
Ulrike
U
Raff
Reinhard
R
Schneider
Stepan
S
Gambaryan
Stefan
S
Seibold
Mark
M
Reber
Nicole
N
Vornberger
Ralf
R
Freund
Lothar
L
Schramm
Christoph
C
Wanner
Jan
J
Galle
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology*; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D007679:Kidney Medulla / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D009000:Monocytes / Q000473:pathology; D009336:Necrosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D001120:Arginine; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases