Effect of theophylline on the initiation phase of postischemic acute renal failure in rats.

These experiments were designed to test, pharmacologically, the hypothesis that adenosine mediates the reduction in glomerular filtration rate (GFR) observed during the initiation phase of postischemic acute renal failure (ARF). Six groups of pentobarbital-anesthetized rats were studied; in all groups, the left renal arteries were completely occluded for either 30 or 45 minutes, and 30 minutes after relieving the occlusion, two consecutive 40-minute clearances were begun. Two control groups received no pretreatment; two experimental groups were pretreated with intravenous theophylline (24 mumol/kg prime followed by 0.28 mumol/min/kg infusion); two further experimental groups were pretreated with a higher dose of theophylline (111 mumol/kg prime followed by 1.1 mumol/min/kg infusion). As assessed by reduction in inulin clearance, the impairment of GFR was directly related to the duration of ischemia. The lower dose of theophylline had no significant effects on inulin clearances of right or left kidneys in either group (previously ischemic for 30 or 45 minutes). The higher dose of theophylline also had no significant effects on right kidney inulin clearances, but it significantly increased the inulin clearances of left kidneys previously ischemic for 30 to 45 minutes. This theophylline-induced increase in inulin clearance after 30 minutes of ischemia was accompanied by an increase in renal plasma flow. Because theophylline is a competitive antagonist at adenosine receptors, these results are consistent with the hypothesis that endogenous adenosine mediates, at least in part, the hemodynamic changes in postischemic ARF in rats.