Preservation of the glomerular capillary ultrafiltration coefficient during rat nephrotoxic serum nephritis by a specific leukotriene D4 receptor antagonist.
Preservation of the glomerular capillary ultrafiltration coefficient during rat nephrotoxic serum nephritis by a specific leukotriene D4 receptor antagonist.
复制标题
特定白三烯 D4 受体拮抗剂对大鼠肾毒性血清肾炎期间肾小球毛细血管超滤系数的保护。
DOI：
10.1172/jci113509
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Ichikawa,I
中科院分区：
文献类型：
--
作者：
Badr,KF;Schreiner,GF;Wasserman,M;Ichikawa,I
白三烯D4是活化白细胞中花生四烯酸的一种有效的生物活性脂氧合酶衍生物，可降低肾小球毛细血管超滤系数（Kf）并收缩培养中的系膜细胞。因此，我们研究了其在介导大鼠实验性肾毒性血清（NTS）诱导的肾小球肾炎后肾单位滤过率降低中的潜在作用。在静脉内给予0.8ml兔血清（组1，n = 6）、0.8ml兔抗大鼠肾小球基底膜抗体（组2，n = 8）或存在（组3，n = 7）新的高度特异性LTD 4受体拮抗剂SK&F 104353后2小时，在等容性Munich-Wistar大鼠中进行微穿刺测量。抗体结合和中性粒细胞浸润的定量显示组2和组3之间无差异。然而，内源性LTD 4作用的拮抗作用与NTS诱导的SNGFR下降的预防有关，因为Kf下降的消除是这种形式的实验性肾小球肾炎的特征。内源性LTD 4的拮抗作用对NTS诱导的肾小球前和肾小球后小动脉阻力增加没有影响，也不影响肾单位血浆流速或净跨毛细血管液压差。观察到LTD 4拮抗剂对肾小球毛细血管的高度局部保护作用表明，在这种形式的肾小球肾炎的病理生理学中，肾小球内释放的LTD 4可能具有重要的功能作用，可能来源于浸润的白细胞。
Leukotriene D4, a potent biologically active lipoxygenase derivative of arachidonic acid in activated leukocytes, depresses the glomerular capillary ultrafiltration coefficient (Kf) and contracts mesangial cells in culture. We therefore investigated its potential role in mediating the reduction in nephron filtration rate seen after induction of experimental nephrotoxic serum (NTS)-induced glomerulonephritis in the rat. Micropuncture measurements were performed in euvolemic Munich-Wistar rats 2 h after i.v. administration of 0.8 ml of rabbit serum (group 1, n = 6), 0.8 ml of rabbit anti-rat glomerular basement membrane antibody in the absence (group 2, n = 8), or presence (group 3, n = 7) of the new highly specific LTD4 receptor antagonist SK&F 104353. Quantitation of antibody binding and neutrophil infiltration revealed no differences between groups 2 and 3. Antagonism of endogenous LTD4 actions, however, was associated with prevention of the NTS-induced fall in SNGFR because of the abrogation of the fall in Kf which characterizes this form of experimental glomerulonephritis. Antagonism of endogenous LTD4 had no effect on the NTS-induced increases in pre- and postglomerular arteriolar resistances, and did not affect nephron plasma flow rate or net transcapillary hydraulic pressure difference. The observed highly localized protective action of the LTD4 antagonist on the glomerular capillary points to a possibly major functional role for intraglomerularly released LTD4, likely originating from infiltrating leukocytes, in the pathophysiology of this form of glomerulonephritis.Images