GLOMERULAR RESPONSES TO PLATELET-ACTIVATING FACTOR IN THE RAT - ROLE OF THROMBOXANE-A2
GLOMERULAR RESPONSES TO PLATELET-ACTIVATING FACTOR IN THE RAT - ROLE OF THROMBOXANE-A2
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DOI：
10.1152/ajprenal.1989.256.1.f35
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发表时间：
1989-01-01
影响因子：
--
通讯作者：
JACOBSON, HR
中科院分区：
文献类型：
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作者：
BADR, KF;DEBOER, DK;JACOBSON, HR
鉴于其在肾小球损伤中作为促炎介质的作用，我们研究了麻醉的正常血容量Munich-Wistar大鼠肾动脉内注射血小板活化因子（PAF）对肾皮质微循环的反应。在没有低血压或血液浓缩的情况下，PAF的近动脉给药导致肾血浆流速（RPF）、肾小球滤过率（GFR）和滤过分数（FF）的剂量依赖性降低。单肾单位（SN）血浆流速（QA）、SNGFR和SNFF也下降[126 . ±. 7到101 .+-. 6nl/min（P < 0.005），40.6 ±. 2.1至21.5 .+-。2.5 nl/min（P < 0.005）和0.33 ± 0.05。0.03至0.21 . ±. 0.03（P < 0.025）]。PAF增加肾小球前和肾小球后小动脉阻力[2.32 . ±-. 0.14至2.73 .+-。0.19（P < 0.005）和1.32 ±. 0.13到1.45 .+-。0.10 1010dyn. cntdot. s.cntdot. cm-5（P < 0.05）]。PAF输注还导致肾小球毛细血管超滤系数Kf [0.058 ± 0.0001]的平均值显著降低。0.012至0.020 ±。0.003 nl. cntdot. s-1.cntdot. mmHg（P < 0.025）]。PAF引起的肾血流动力学改变在环氧化酶抑制剂吲哚美辛和布洛芬的存在下被消除。当与血栓素A2（TxA 2）受体拮抗剂同时给药时，PAF导致RPF和GFR显著增加。在离体肾小球中，PAF以剂量依赖性方式刺激TxB 2的生物合成。PAF通过收缩小动脉和系膜平滑肌抑制肾小球功能。这些作用可能通过TxA 2的次级释放介导。
In view of its role as a proinflammatory mediator in glomerular injury, we investigated the renal cortical microcirculatory responses to the intrarenal arterial administration of platelet-activating factor (PAF) in the anesthetized euvolemic Munich-Wistar rat. Close arterial administration of PAF led to dose-dependent reductions in renal plasma flow rate (RPF), glomerular filtration rate (GFR), and filtration fraction (FF), in the absence of hypotension or hemoconcentration. Single-nephron (SN) plasma flow rate (QA), SNGFR and SNFF also fell [126 .+-. 7 to 101 .+-. 6 nl/min (P < 0.005), 40.6 .+-. 2.1 to 21.5 .+-. 2.5 nl/min (P < 0.005), and 0.33 .+-. 0.03 to 0.21 .+-. 0.03 (P < 0.025)]. PAF increased pre- and postglomerular arteriolar resistances [2.32 .+-. 0.14 to 2.73 .+-. 0.19 (P < 0.005) and 1.32 .+-. 0.13 to 1.45 .+-. 0.10 1010dyn .cntdot. s .cntdot. cm-5 (P < 0.05)]. PAF infusion also led to a dramatic reduction in the mean value for the glomerular capillary ultrafiltration coefficient, Kf [0.058 .+-. 0.012 to 0.020 .+-. 0.003 nl .cntdot. s-1 .cntdot. mmHg (P < 0.025)]. PAF-incuded changes in renal hemodynamics were abolished in the presence of the cyclooxygenase inhibitors, indomethacin and ibuprofen. When administered concomitantly with a thromboxane A2 (TxA2) receptor antagonist, PAF led to significant increases in RPF and GFR. In isolated glomeruli, PAF stimulated the biosynthesis of TxB2 in a dose-dependent manner. Thus PAF depresses rat glomerular function by inducing contraction of arteriolar and mesangial smooth muscle. These effects are likely mediated via the secondary release of TxA2.