[Progression of chronic renal failure in remnant rats: role of arginase inhibition].
BACKGROUND
Oral administration of arginine to remnant (REM) rats (5/6 nx) slows the progression of chronic renal failure through a nitric-oxide(NO)-dependent mechanism. We have recently shown that inhibition of arginase, the main metabolic pathway of arginine, was able to induce similar results on renal dynamics (GIN: 2001, 18:285-290). Aim of the present study was to test whether these changes were mediated by increased availability of arginine-derived NO. Methods. Three Groups of REM rats were studied for 8 weeks after surgery: 1) untreated REM (Group REM); 2) REM rats treated with arginine (1%) in tap water (Group ARG); 3) REM rats administered a Mn++-free diet, to induce partial inhibition of arginase (Group MNF). Normal unmanipulated rats were used as controls (Group NOR).


RESULTS
Liver arginase activity was significantly depressed only in MNF-rats (-35% vs. REM, p < 0.01). Blood pressure was significantly lower in Group MNF vs. ARG and REM after 6 weeks (p < 0.05). Proteinuria was significantly decreased in Group ARG (-42%, p < 0.05 vs. REM) and even more in Group MNF (-57%, p < 0.01). ARG plasma levels, decreased in REM rats (-41% vs. Group CON), were normalized in Group ARG (p < 0.01 vs. Group REM); arginase inhibition was able to increase such levels in Group MNF (+38% vs. REM) and this resulted in a proportional rise in urinary nitrite excretion (+33% vs. REM), grossly depressed in REM rats. Renal arginase activity was lower in all the Groups of remnant rats vs. Group NOR, but intrarenal concentrations of ARG were significantly lower only in rats of Group MNF (p < 0.05 vs. all the other Groups). Histological examination showed that MNF-rats had a glomerular sclerosis index lower than in the other Groups (p < 0.05 vs. Group REM and ARG).


CONCLUSIONS
In conclusion, inhibition of arginase in remnant rats slows the progression of CRF and preserves renal histology through a direct and/or indirect NO-dependent mechanism.
Pisani
A
A
Cattedra di Nefrologia Medica, Università degli Studi Federico II, Napoli.
Uccello
F
F
Cesaro
A
A
Alfieri
R
R
Comi
N
N
Mirenghi
F
F
Serio
V
V
Sabbatini
M
M
D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors*; D018450:Disease Progression; D007676:Kidney Failure, Chronic / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001119:Arginase