Inhibition of thromboxane synthesis ameliorates the progressive kidney disease of rats with subtotal renal ablation.
Inhibition of thromboxane synthesis ameliorates the progressive kidney disease of rats with subtotal renal ablation.
复制标题
抑制血栓素合成可改善肾次全消融大鼠的进行性肾病。
DOI：
10.1073/pnas.82.1.193
复制
发表时间：
1985
影响因子：
11.1
通讯作者：
Klahr,S
中科院分区：
文献类型：
--
作者：
Purkerson,ML;Joist,JH;Yates,J;Valdes,A;Morrison,A;Klahr,S
切除大鼠超过70%的肾脏肿块会导致高血压、蛋白尿和残余肾脏的肾小球硬化。与正常大鼠相比，残肾大鼠的尿中血栓素排泄量增加。在残留肾脏的大鼠中，长期口服血栓素合成抑制剂OKY 1581可增加肾脏血流量和肾小球滤过率(GFR)，减少尿中蛋白质和血栓素的排泄，降低血压和心脏指数，并改善肾脏组织学。给予OKY 1581对残肾肥大程度无影响。服用oky 1581的残肾大鼠的单肾单位血浆流量和肾小球滤过率的计算值明显大于注射生理盐水的大鼠。急性静脉注射。给予OKY 1581可增加残肾大鼠的肾血浆流量和肾小球滤过率，但对正常大鼠或先前用乙酰水杨酸治疗的残肾大鼠无影响。OKY 1581可显著抑制血小板聚集。我们认为，在这种肾脏疾病模型中，血小板聚集和肾小球内血栓形成在肾小球硬化的发展中起着关键作用。抑制血小板聚集可防止肾小球硬化、高血压和心肌肥厚的发生。我们认为残留肾小球发生的高灌流和高滤过本身并不是肾小球硬化的直接原因。
Ablation of greater than 70% of renal mass in the rat results in hypertension, proteinuria, and glomerular sclerosis of the remnant kidney. Rats with a remnant kidney have increased excretion of thromboxane in the urine when compared with normal rats. Chronic oral administration of OKY 1581, an inhibitor of thromboxane synthesis, in rats with a remnant kidney increases renal blood flow and glomerular filtration rate (GFR), decreases protein and thromboxane excretion in the urine, lowers blood pressure and cardiac index, and improves renal histology. The degree of hypertrophy of the remnant kidney was unaffected by administration of OKY 1581. Calculated values for single nephron plasma flow and GFR were significantly greater in rats with remnant kidneys given OKY 1581 than in rats given saline. Acute i.v. administration of OKY 1581 increased renal plasma flow and GFR in rats with a remnant kidney but not in normal rats or rats with a remnant kidney previously treated with acetylsalicyclic acid. OKY 1581 markedly inhibited platelet aggregation. We suggest that in this model of renal disease platelet aggregation and intraglomerular thrombosis play a key role in the development of glomerulosclerosis. Inhibition of platelet aggregation prevents development of glomerulosclerosis, hypertension, and cardiac hypertrophy. We suggest that hyperperfusion and hyperfiltration per se occurring in remnant glomeruli are not directly responsible for the development of glomerulosclerosis.