Tubular and glomerular L-arginine transport (uptake and transporters) and the nitric oxide synthases in ischemic acute renal failure (iARF) in streptozotocin-induced diabetic rats (STZ-DM).
BACKGROUND
L-arginine or its metabolites may be important pathogenetic factors in ischemic acute renal failure (iARF) in rats. It was found that the L-arginine-nitric oxide synthase-nitric oxide system plays an important role in the renal hemodynamic alterations in the early stages of diabetes. The iARF in diabetic rats is much more severe than the normal rats exposed to a same ischemia time. The purpose of the present study was to evaluated L-arginine uptake and its transporters and nitric oxide synthase isoform expression in tubuli and glomeruli of STZ-induced diabetic rats with iARF.


METHODS
iARF was induced by right nephrectomy and left renal artery clamping for 60 min followed by a 60 min reflow period. iARF was induced in STZ diabetes rats two weeks after intraperitoneal streptozotocin (60 mg/kg body weight) and in normal control rats. L-arginine uptake, L-arginine transporters (CAT1 and CAT2) and nitric oxide synthases (iNOS, eNOS, and bNOS) were determined by RT-PCR) in both glomeruli and tubuli preparations.


RESULTS
The STZ diabetic rats compared with the non diabetic normal rats have a higher glomerular L-arginine uptake, higher iNOS mRNA, lower eNOS mRNA, and lower tubular CAT1 mRNA, eNOS mRNA, and bNOS mRNA. The diabetic iARF after one hour of reperfusion had lower glomerular L-arginine uptake, lower CAT1 mRNA, lower eNOS mRNA, lower bNOS, and higher tubular iNOS mRNA compared with iARF in normal rats.


CONCLUSIONS
Our findings suggest a prolonged and more severe post-glomerular vasoconstriction very early after the reflow in the iARF of STZ diabetic rats compared with the iARF in the normal control rats. That may be a plausible explanation to the very significant decline in GFR and tubular necrosis that characterize the iARF in diabetic rats.
Levin-Iaina
Nomy
N
Department of Nephrology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. lironomy@gmail.com
Schwartz
Idit
I
Chernichovsky
Tamara
T
Davidovitch
Aron
A
Iaina
Adrian
A
Schwartz
Doron
D
D058186:Acute Kidney Injury / Q000150:complications / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D027201:Cationic Amino Acid Transporter 1 / Q000378:metabolism; D027202:Cationic Amino Acid Transporter 2 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009399:Nephrons / Q000201:enzymology / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D015427:Reperfusion Injury / Q000378:metabolism
D027201:Cationic Amino Acid Transporter 1; D027202:Cationic Amino Acid Transporter 2; D007527:Isoenzymes; D012333:RNA, Messenger; D001120:Arginine; D019001:Nitric Oxide Synthase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases