Effect of the selective A1 adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine on acute renal dysfunction induced by Escherichia coli endotoxin in rats

J Pharm Pharmacol. 1993 Nov;45(11):979-84. doi: 10.1111/j.2042-7158.1993.tb05640.x.

Abstract

The effect of the selective A1 adenosine antagonist, 8-cyclopentyl-1,3-dipropylxanthine (CPX), on Escherichia coli endotoxin-induced acute renal dysfunction was determined in anaesthetized rats. Bolus administration of endotoxin at doses of either 1 or 20 mg kg-1 evoked decreases in inulin clearance, renal blood flow, urine flow and excretion of sodium, potassium and chloride. The changes in renal function produced by 20 mg kg-1 endotoxin were more severe than those noted with 1 mg kg-1 toxin and, by contrast to this lower dose, renal function showed no signs of recovery. Intravenous administration of CPX (0.1 mg kg-1) elicited a statistically significant, although modest, attenuation of the decline in inulin clearance, renal blood flow, urine output and electrolyte excretion induced by 20 mg kg-1 endotoxin. By contrast, treatment with 0.1 mg kg-1 CPX resulted in statistically significant protection against the falls in excretory function evoked by 1 mg kg-1 endotoxin but not against the reductions in renal blood flow and inulin clearance produced by the lower dose of toxin. These results suggest that adenosine may play a role, albeit not a major one, in the pathophysiology of endotoxaemic acute renal failure.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / physiopathology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Chlorides / urine
  • Endotoxins*
  • Escherichia coli*
  • Inulin
  • Kidney Function Tests
  • Male
  • Potassium / urine
  • Purinergic P1 Receptor Antagonists*
  • Rats
  • Rats, Wistar
  • Renal Circulation / drug effects
  • Sodium / urine
  • Urodynamics / drug effects
  • Xanthines / therapeutic use*

Substances

  • Chlorides
  • Endotoxins
  • Purinergic P1 Receptor Antagonists
  • Xanthines
  • Inulin
  • Sodium
  • 1,3-dipropyl-8-cyclopentylxanthine
  • Potassium