Atorvastatin improves the course of ischemic acute renal failure in aging rats

J Am Soc Nephrol. 2004 Apr;15(4):901-9. doi: 10.1097/01.asn.0000119573.01290.ae.

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.

MeSH terms

  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / pathology
  • Animals
  • Atorvastatin
  • Heptanoic Acids / therapeutic use*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Ischemia / etiology*
  • Ischemia / pathology
  • Kidney / blood supply*
  • Kidney / pathology
  • Male
  • Pyrroles / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Atorvastatin