Jocks T, Zahner G, Helmchen U, Kneissler U, Stahl R A
Department of Medicine, University of Hamburg, Germany.
Am J Physiol. 1996 Jan;270(1 Pt 2):F179-85. doi: 10.1152/ajprenal.1996.270.1.F179.
To evaluate the effect of antibody and complement on renal hemodynamic changes, glomerular injury was induced in isolated perfused kidneys by an anti-thymocyte antibody (ATS) and rat serum (RS). Glomerular filtration rate (GFR), renal vascular resistance (RVR), and renal perfusate flow (RPF) were assessed over an 80-min period. The possible role of thromboxane (Tx) was tested by the application of the Tx synthesis inhibitor UK-38485 and the Tx receptor blocker daltroban. Perfusion of kidneys with ATS and RS significantly reduced GFR at 10 min (control, 501 +/- 111; ATS + RS, 138 +/- 86 ml.g kidney-1.min-1, significance of F = 0.000) after RS. Similarly, RPF (ml.g kidney-1.min-1) fell from 19.2 +/- 1.8 to 6.1 +/- 2.0 (significance of F = 0.000), whereas RVR (mmHg.ml-1.g.min) increased threefold from 5.2 +/- 0.4 to 17.9 +/- 5.0 at 10 min. These changes were ameliorated by the pretreatment of the rats with daltroban and UK-38485. Addition of erythrocytes to the perfusate increased RVR and GFR, whereas RPF decreased compared with cell-free perfused kidneys. ATS and RS in this preparation also decrease GFR and RPF. The hemodynamic alterations appeared without changes in filtration fraction. Compared with untreated, perfused control kidneys, glomerular Tx formation was significantly increased in ATS and RS perfused kidneys. These data demonstrate that antibody and RS induce impairment of renal hemodynamics, which are mediated by increased Tx formation.
为评估抗体和补体对肾脏血流动力学变化的影响，通过抗胸腺细胞抗体（ATS）和大鼠血清（RS）在离体灌注肾中诱导肾小球损伤。在80分钟内评估肾小球滤过率（GFR）、肾血管阻力（RVR）和肾灌注液流量（RPF）。通过应用血栓素（Tx）合成抑制剂UK - 38485和Tx受体阻滞剂达曲班来测试Tx的可能作用。用ATS和RS灌注肾脏在RS灌注后10分钟时显著降低GFR（对照组，501±111；ATS + RS组，138±86 ml·g肾-1·min-1，F值的显著性=0.000）。同样，RPF（ml·g肾-1·min-1）从19.2±1.8降至6.1±2.0（F值的显著性=0.000），而RVR（mmHg·ml-1·g·min）在10分钟时从5.2±0.4增加了三倍至17.9±5.0。用达曲班和UK - 38485预处理大鼠可改善这些变化。向灌注液中添加红细胞会增加RVR和GFR，而与无细胞灌注的肾脏相比RPF降低。此制剂中的ATS和RS也会降低GFR和RPF。血流动力学改变出现时滤过分数无变化。与未处理的灌注对照肾脏相比，ATS和RS灌注的肾脏中肾小球Tx形成显著增加。这些数据表明抗体和RS诱导肾脏血流动力学受损，这是由Tx形成增加介导的。
