Effect of the selective A1 adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine on acute renal dysfunction induced by Escherichia coli endotoxin in rats.
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.
Knight
R J
RJ
Department of Pharmacology, University of Leeds, UK.
Bowmer
C J
CJ
Yates
M S
MS
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D002712:Chlorides / Q000652:urine; D004731:Endotoxins; D004926:Escherichia coli; D007444:Inulin; D007677:Kidney Function Tests; D008297:Male; D011188:Potassium / Q000652:urine; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D014563:Urodynamics / Q000187:drug effects; D014970:Xanthines / Q000627:therapeutic use*
D002712:Chlorides; D004731:Endotoxins; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; D007444:Inulin; D012964:Sodium; C051360:1,3-dipropyl-8-cyclopentylxanthine; D011188:Potassium