Gerkens J F
University of Newcastle, Royal Newcastle Hospital, NSW, Australia.
Eur J Pharmacol. 1990 Feb 27;177(3):119-26. doi: 10.1016/0014-2999(90)90261-4.
The vasodilator effect of platelet-activating factor (PAF) and its reproducibility was determined in rat kidneys perfused in situ with blood or in isolated kidneys perfused with Krebs solution or Krebs plus 0.25% bovine serum albumin (BSA) at 3 ml/min. Dilatation was measured as inhibition of the increase in perfusion pressure produced by stimulation of the renal nerves or by infusion of noradrenaline. PAF, in saline and 0.25% BSA, was infused into the perfusate at 0.05 ml/min to produce eight incremental consecutive concentrations from 3 x 10(-11) to 10(-7). Two sets of PAF infusions were made during nerve-stimulated responses followed by one set during noradrenaline infusion. With blood perfusion, PAF consistently produced dose-dependent dilatation and 3 x 10(-9) M reduced nerve-stimulated responses to 52% of control. This effect was reproduced by a second infusion. However in Krebs-perfused kidneys the effect of the first PAF infusion was not consistent, with responses either not affected or reduced only at the lower doses so that the mean maximum decrease was only 10% and the vasodilatation was not dose-dependent. The second PAF infusion invariably had no effect. On the other hand perfusion with Krebs and 0.25% BSA produced consistent and dose-dependent inhibition of vasoconstriction which was reproduced by a second infusion. PAF was effective at 10-fold lower doses in Krebs-albumin perfused compared to blood-perfused kidneys. These results indicate that exogenous PAF is a potent and reproducible dilator of the rat renal vasculature perfused with blood or Krebs-albumin solution but not albumin-free Krebs solution.
在以3毫升/分钟的速度用血液原位灌注的大鼠肾脏中,或在以克雷布斯溶液或含0.25%牛血清白蛋白(BSA)的克雷布斯溶液灌注的离体肾脏中,测定了血小板活化因子(PAF)的血管舒张作用及其可重复性。通过抑制肾神经刺激或去甲肾上腺素输注引起的灌注压力升高来测量血管舒张。将溶于生理盐水和0.25% BSA中的PAF以0.05毫升/分钟的速度注入灌流液中,以产生从3×10⁻¹¹到10⁻⁷的八个连续递增浓度。在神经刺激反应期间进行两组PAF输注,随后在去甲肾上腺素输注期间进行一组输注。在血液灌注时,PAF始终产生剂量依赖性舒张,3×10⁻⁹ M可将神经刺激反应降低至对照的52%。第二次输注再现了这种效果。然而,在克雷布斯溶液灌注的肾脏中,第一次PAF输注的效果不一致,反应要么不受影响,要么仅在较低剂量下降低,因此平均最大降低仅为10%,且血管舒张不依赖剂量。第二次PAF输注始终无效。另一方面,用克雷布斯溶液和0.25% BSA灌注产生了一致的、剂量依赖性的血管收缩抑制,第二次输注再现了这种抑制。与血液灌注的肾脏相比,在克雷布斯-白蛋白灌注的肾脏中,PAF在低10倍的剂量下就有效。这些结果表明,外源性PAF是灌注血液或克雷布斯-白蛋白溶液的大鼠肾血管系统的一种强效且可重复的舒张剂,但不是无白蛋白的克雷布斯溶液的舒张剂。