[Effects of atorvastatin on ischemic acute renal failure in aging rats]. / Effetti della atorvastatina nell'insufficienza renale acuta ischemica del ratto anziano.

BACKGROUND: Aging (O) rats have a greater susceptibility to renal ischemia than young (Y) rats due to an endothelial dysfunction partially reversed by exogenous administration of L-Arginine. Since statins are able to increase nitric oxide (NO) production, aim of the study was to evaluate whether pre-treatment with atorvastatin (ATO, 10 mg/kg/day for 12 days), had positive effects on ischemic acute renal failure (ARF) of aging rats. METHODS: Renal clearance studies (inulin) were performed 24 hours after ischemia in 6 Groups (n=6 in each Group) of both Y- and O-rats: control rats (CON), untreated rats with ARF (Groups IRA), and rats with ARF but pretreated with ATO (Groups ATO+IRA). RESULTS: Renal ischemia determined a sharper decrease in GFR of Group O-IRA than Y-IRA (-80% and -63% vs respective CON, both p<0.001). In both Groups the fall in GFR was secondary to renal vasoconstriction and the consequent reduction in renal plasma flow. Pre-treatment with ATO did not modify GFR in Group Y-ATO+IRA, but was able to determine a marked rise in GFR of rats of O-ATO+IRA Group (+100% vs O-IRA), through a reduction in renal vascular resistances. Induction of ARF greatly enhanced nitrate excretion in Group Y-IRA, but slightly affected Group O-ARF. Administration of ATO did not modify nitrite excretion in Y rats, whereas it was able to increase nitrate excretion in O-ATO+ARF rats (+111% vs O-IRA). CONCLUSIONS: Pre-treatment with ATO is able to improve the renal response to ischemia in aging rats, through a mechanism which likely is NO-dependent.

[Progression of chronic renal failure in remnant rats: role of arginase inhibition]. / Progressione dell'insufficienza renale cronica nel ratto remnant: ruolo della inibizione dell'arginasi.

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.