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.
Raff
Ulrike
U
Division of Nephrology, Department of Medicine, Julius Maximilian University, Würzburg, Germany.
Schneider
Reinhard
R
Gambaryan
Stepan
S
Seibold
Stefan
S
Reber
Mark
M
Vornberger
Nicole
N
Freund
Ralf
R
Schramm
Lothar
L
Wanner
Christoph
C
Galle
Jan
J
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