Allopurinol and enalapril failed to conserve urinary NOx and sodium in ischemic acute renal failure in spontaneously hypertensive rats

Am J Nephrol. 2006;26(4):388-99. doi: 10.1159/000094936. Epub 2006 Aug 8.

Abstract

Background: Ischemia-reperfusion-induced acute renal failure (ARF) is associated with a high mortality in patients with hypertension and with an unfavorable outcome of kidney transplants from marginal donors.

Aim: The influence of allopurinol and enalapril on urinary nitrate/nitrite (UNOx), glomerular filtration rate, plasma and urinary sodium, and hemodynamic parameters was examined in spontaneously hypertensive rats (SHR) with ARF.

Methods: ARF was induced by right-kidney removal and clamping the left renal artery for 40 min in 50 male 26-week-old SHR weighing 300 +/- 23 g. The rats were randomly allocated to five groups: (1) sham operated; (2) ARF; (3) ARF after pretreatment with 40 mg/kg allopurinol; (4) ARF after pretreatment with 40 mg/kg enalapril, and (5) ARF after pretreatment with 40 mg/kg allopurinol and 40 mg/kg enalapril. Creatinine clearance, UNOx (Griess reaction), cardiac output (dye dilution technique), mean arterial blood pressure, and renal blood flow were measured 24 h after reperfusion. Total vascular resistance and renal vascular resistance were calculated and compared between the groups.

Results: A nonsignificant decrease was found in both daily UNOx excretion and creatinine clearance when pretreated ARF groups and the ARF group without pretreatment were compared (p > 0.05). Significantly lower plasma sodium values (139.5 +/- 4.86 mmol/l) in the allopurinol-pretreated ARF group were found than in the ARF group without pretreatment, in the ARF group pretreated with enalapril, and in the sham SHR group (p = 0.029). The urinary sodium loss was greater in the enalapril-pretreated than in the allopurinol-pretreated ARF group (p = 0.047). Allopurinol and/or enalapril pretreatment decreased total vascular resistance (p = 0.003) in comparison with the sham SHR group.

Conclusion: Neither allopurinol nor enalapril nor both were protective against ischemia-reperfusion injury in SHR, nor altered glomerular filtration rate and UNOx in a favorable direction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / prevention & control
  • Acute Kidney Injury / urine*
  • Allopurinol / administration & dosage*
  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antimetabolites / administration & dosage
  • Drug Combinations
  • Enalapril / administration & dosage*
  • Male
  • Nitrates / urine*
  • Nitrites / urine*
  • Rats
  • Rats, Inbred SHR
  • Reperfusion Injury / complications
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / prevention & control
  • Sodium / urine*
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Antimetabolites
  • Drug Combinations
  • Nitrates
  • Nitrites
  • Allopurinol
  • Enalapril
  • Sodium