Reyes A A, Klahr S
Renal Division, Washington University School of Medicine, St. Louis, Missouri 63110.
Proc Soc Exp Biol Med. 1991 Oct;198(1):572-8. doi: 10.3181/00379727-198-43291.
Platelet-activating factor (PAF) is a powerful vasodilator with important effects on kidney function. It has been suggested that the renal effects of PAF are mediated by thromboxane A2 (TxA2). We examined the effect of PAF on renal function in sham-operated rats and rats that had undergone unilateral release of bilateral ureteral obstruction (BUO) of 24-hr duration, a condition in which the synthesis of TxA2 is increased. To eliminate systemic hemodynamic changes, PAF was infused directly into the left renal artery using the lowest dose that affected renal function (2.3 x 10(-13) moles/min). Infusion of PAF significantly decreased the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in normal rats and rats with BUO. Normal (sham-operated) rats pretreated with an inhibitor of TxA2 synthesis also had a significant decrease in GFR after administration of PAF (ERPF also decreased, but not significantly). Rats with BUO pretreated with an inhibitor of TxA2 synthesis had significantly greater basal GFR and ERPF (increases of 72 and 171%, respectively) than untreated BUO rats. Administration of PAF to the former group further increased GFR and ERPF (by 37 and 39%, respectively; P less than 0.001). The role of endogenous PAF was evaluated by administering a specific PAF receptor antagonist. Sham-operated rats pretreated with high doses of the PAF receptor antagonist had significantly higher mean arterial pressure values than normal untreated rats, and had no decrease in GFR and ERPF during PAF infusion. Rats with BUO pretreated with the PAF antagonist had a significant, dose-dependent decrease in basal GFR and ERPF. These data suggest that endogenous PAF has a vasodilatory role in obstructive nephropathy. No significant differences in eicosanoid excretion in the urine corrected per GFR were observed during infusion of PAF in any of the groups examined. In BUO rats with intact TxA2 synthesis, exogenous administration of PAF decreased renal function, presumably through further increases in the production of TxA2. However, when TxA2 production was inhibited, PAF administration increased GFR and ERPF, presumably due to its unopposed vasodilatory properties. The data suggest an important role of PAF in the hemodynamic changes seen in obstructive nephropathy.
血小板活化因子（PAF）是一种强大的血管舒张剂，对肾功能有重要影响。有人提出，PAF的肾脏效应是由血栓素A2（TxA2）介导的。我们研究了PAF对假手术大鼠和经历了24小时双侧输尿管梗阻（BUO）单侧解除的大鼠肾功能的影响，在这种情况下TxA2的合成增加。为消除全身血流动力学变化，使用影响肾功能的最低剂量（2.3×10⁻¹³摩尔/分钟）将PAF直接注入左肾动脉。注入PAF显著降低了正常大鼠和BUO大鼠的肾小球滤过率（GFR）和有效肾血浆流量（ERPF）。用TxA2合成抑制剂预处理的正常（假手术）大鼠在给予PAF后GFR也显著降低（ERPF也降低，但不显著）。用TxA2合成抑制剂预处理的BUO大鼠的基础GFR和ERPF显著高于未处理的BUO大鼠（分别增加72%和171%）。向前一组给予PAF进一步增加了GFR和ERPF（分别增加37%和39%；P＜0.001）。通过给予特异性PAF受体拮抗剂评估内源性PAF的作用。用高剂量PAF受体拮抗剂预处理的假手术大鼠的平均动脉压值显著高于未处理的正常大鼠，并且在注入PAF期间GFR和ERPF没有降低。用PAF拮抗剂预处理的BUO大鼠的基础GFR和ERPF有显著的剂量依赖性降低。这些数据表明内源性PAF在梗阻性肾病中具有血管舒张作用。在任何检查的组中，注入PAF期间，按GFR校正的尿中类花生酸排泄没有显著差异。在TxA2合成完整的BUO大鼠中，外源性给予PAF降低了肾功能，推测是通过进一步增加TxA2的产生。然而，当TxA2产生被抑制时，给予PAF增加了GFR和ERPF，推测是由于其无对抗的血管舒张特性。数据表明PAF在梗阻性肾病中所见的血流动力学变化中起重要作用。
