title: Atorvastatin improves the course of ischemic acute renal failure in aging rats.
abstract: Statins increase the production of nitric oxide (NO) and have beneficial effects on the course of acute renal failure (ARF) in young rats. The effects of a short-term treatment with atorvastatin (ATO) on ischemic ARF in old rats, characterized by a great susceptibility to ischemia, was tested. No difference was found in renal dynamics between young (Y, 3 mo old) and old (O, 18 mo old) rats in normal conditions (CON) or after ATO treatment (12 mg/kg/d for 14 d). Twenty-four hours after clamping of both renal arteries, a more pronounced decrease in GFR was observed in O rats versus Y rats after a greater renal vasoconstriction and hypoperfusion of aging animals. Pretreatment with ATO mitigated renal vasoconstriction in O rats and restored GFR values to Y rats. Nitrate excretion was enhanced in Y rats after ARF but was not further modified by ATO; in O rats, ARF did not increase nitrate excretion, which was raised after ATO treatment. This reflected the increase in endothelial NO synthase (eNOS)-mRNA expression and eNOS protein observed in old ATO-treated animals with ARF. ATO treatment had also a significant protective effect against the cell injury at tubular level in O, but not Y, rats. The Ras system was not influenced by ATO in O rats, whereas the activation of Rho proteins was partially inhibited by ATO. Low-dose treatment with ATO enhances NO availability in aging rats, improving renal dynamics and conferring a peculiar histologic protection at tubular level after ischemia.
authors.affiliation: Department of Nephrology, University Federico II, Via A. Manzoni 50, 80123 Naples, Italy. sabbatin@unina.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Sabbatini
authors.forename: Antonio
authors.initials: A
authors.lastname: Pisani
authors.forename: Francesco
authors.initials: F
authors.lastname: Uccello
authors.forename: Vittorio
authors.initials: V
authors.lastname: Serio
authors.forename: Rosalba
authors.initials: R
authors.lastname: Serù
authors.forename: Roberto
authors.initials: R
authors.lastname: Paternò
authors.forename: Bruno
authors.initials: B
authors.lastname: Cianciaruso
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fuiano
authors.forename: Michele
authors.initials: M
authors.lastname: Andreucci
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000069059:Atorvastatin; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007511:Ischemia / Q000209:etiology* / Q000473:pathology; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D008297:Male; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin