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

Abstract

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.