[Effects of atorvastatin on ischemic acute renal failure in aging rats].
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.
Pisani
A
A
Cattedra di Nefrologia Medica, Universita' Federico II, Napoli, Italy.
Uccello
F
F
Cesaro
A
A
Comi
N
N
Mirenghi
F
F
Serio
V
V
Sabbatini
M
M
D058186:Acute Kidney Injury / Q000178:diet therapy / Q000188:drug therapy* / Q000473:pathology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000069059:Atorvastatin; D018753:Diet, Protein-Restricted; D004198:Disease Susceptibility; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000473:pathology; D005919:Glomerular Filtration Rate; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006984:Hypertrophy; D007444:Inulin / Q000097:blood; D007511:Ischemia / Q000188:drug therapy*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D008026:Ligation; D008297:Male; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D011292:Premedication; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery
D006538:Heptanoic Acids; D020030:Nitric Oxide Donors; D011758:Pyrroles; D007444:Inulin; D000069059:Atorvastatin