Platelet activating factor antagonism with BN52021 protects the kidney against acute ischemic injury

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The present study has been conducted to evaluate the eventual role of the platelet activating factor (PAF) in post-ischemic recovery of renal function, using BN52021, a PAF receptor antagonist, in the anesthetized rat. In Groups 1 and 2, animals were maintained hydropenic (fractional excretion of sodium <1%), while in Groups 3 and 4, studies were performed under extracellular expansion (0.9% NaCl, 5% of body weight), a procedure known to protect the kidney from ischemic injury. Groups 1 and 3 (control animals) were untreated, whereas Groups 2 and 4 received an intravenous bolus of BN52021 (3mg/kg), immediately before clearance studies. After three 20-minute control periods, the left renal artery was occluded during 30 minutes. Four consecutive 20-minute clearance periods were taken after the release of occlusion. In Groups 1 and 2, urine flow (UV) increased from 3.1±0.9 to 20.9±3.6 ml/min, and from 6.8±0.3 to 40.4±4.5 ml/min, respectively, from control to the last period of recovery. Glomerular filtration (GFR) recovered to 38% of control values, from 0.58±0.09 to 0.22±0.10 ml/min in Group 1, as opposed to Group 2, where GFR recovered to 69%, from 0.61±0.07 to 0.42±0.06 ml/min. Urinary sodium (UNaV) increased from 0.3±0.1 to 3.0±0.9 μEq/min, and from 1.0±0.3 to 6.0±0.7 μEq/min, in Groups 1 and 3. UV rose from 14.3±2.5 to 35.3±3.5 μl/min, and from 14.2±2.1 to 68.6±9.3 μl/min, in Groups 3 and 4, during the same periods. GFR only recovered to 21% of control values, from 0.72±0.06 to 0.15±0.05 ml/min in Group 3, while it reached 44% of control values, from 0.78±0.06 to 0.34±0.07 ml/min in Group 4. UNaV increased from 3.4±0.3 to 5.6±1.1 μEq/min, and from 3.1±0.8 to 10.8±1.8 μEq/min, in Groups 3 and 4. The results show that BN52021 markedly improved the recovery of GFR after acute ischemic renal injury. BN52021 treated rats also exhibited a better ability to excrete fluid and sodium, despite partial recovery of GFR. These results suggest that endogenous PAF could play a deleterious role in acute ischemic renal injury.