Benigni A, Zoja C, Corna D, Orisio S, Longaretti L, Bertani T, Remuzzi G
Mario Negri Institute for Pharmacological Research, Division of Nephrology and Dialysis, Ospedali Riuniti di Bergamo, Italy.
Kidney Int. 1993 Aug;44(2):440-4. doi: 10.1038/ki.1993.263.
We have recently reported that renal preproendothelin-1 gene is up-regulated in rats with renal mass reduction (RMR) and that time-dependent increase in urinary excretion of the corresponding peptide correlates with renal disease progression. Here we evaluated whether a specific endothelin subtype A (ETA) receptor antagonist, FR139317, reduced signs of disease activity in this model. Two groups of rats were given FR139317 or its vehicle (saline) from day 7 to day 60 after the surgical procedure. Sham-operated animals were the control group. Blood pressure, urinary protein excretion and serum creatinine were evaluated at days 0, 7 (before FR139317 or saline administration), 30, 45 and 60. At sacrifice, histological evaluation of renal tissue was performed. The results showed that ETA receptor blocker reduced the abnormal permeability to proteins, limited glomerular injury and prevented renal function deterioration thus confirming the working hypothesis. These findings suggest that this class of compounds may eventually prove useful in the treatment of human progressive nephropathies.
我们最近报道，肾前内皮素-1基因在肾质量减少（RMR）的大鼠中上调，并且相应肽的尿排泄量随时间的增加与肾脏疾病进展相关。在此，我们评估了一种特异性内皮素A（ETA）受体拮抗剂FR139317是否能减轻该模型中的疾病活动迹象。两组大鼠在手术操作后第7天至第60天给予FR139317或其溶媒（生理盐水）。假手术动物作为对照组。在第0、7天（给予FR139317或生理盐水之前）、30、45和60天评估血压、尿蛋白排泄和血清肌酐。处死时，对肾组织进行组织学评估。结果表明，ETA受体阻滞剂降低了对蛋白质的异常通透性，限制了肾小球损伤并防止了肾功能恶化，从而证实了工作假设。这些发现表明，这类化合物最终可能被证明对治疗人类进行性肾病有用。
