Ishikawa A, Fujita K, Suzuki K
Department of Urology, Hamamatsu University School of Medicine, Japan.
J Urol. 1997 Feb;157(2):739-42.
We examined the effect of temocapril (Tem), an angiotensin converting enzyme inhibitor (ACEI), on the cyclosporine-induced nephrotoxicity (CsA-NT) in rats.
Male Wistar rats were used. Group 1 (G1) received a medium (i.e. olive oil) only, group 2 (G2) received CsA (30 mg./kg./d) only, group 3 (G3) received both CsA (30 mg./kg./d) and Tem (80 micrograms./kg./d), and group 4 (G4) received Tem (80 micrograms./kg./d) only. Each group consisted of 5 animals. Drugs were given orally for fourteen days. Then, renal cortical blood flow (RCBF) and concentrations of serum creatinine (S-Cr), serum potassium (S-K), whole blood CsA (WB-CsA), serum aldosterone (Ald), and plasma renin activity (PRA) were measured. The creatinine clearance (CCr) was also calculated. Kidneys were processed to the light microscopic examination with Bowie stain, and the size of the renin granules (S-RGs) was estimated by an image analysis system.
G2 showed a decrease of RCBF (p < 0.01), an increase of S-Cr (p < 0.01), a decrease of CCr (p < 0.01), an increase of S-K (p < 0.05), and an increase of S-RGs (p < 0.01). Compared with G2, G3 showed significant improvement in RCBF (p < 0.01) and S-Cr (p < 0.05), but still showed significant impairments in all indices (p < 0.01 or p < 0.05, vs control). G4 showed no remarkable changes comparing with G1, except a significant (p < 0.01, vs. control) increase of S-K. G3 showed additional effect on the increase of S-K (p < 0.01, vs. control and G2). Tem showed no significant influence on the WB-CsA level. The serum Ald and PRA levels were not significantly changed by these drugs.
These data are compatible with the hypothesis that the vasoconstriction of the afferent arterioles (AAs) is a principal mechanism of CsA-NT. The increase of RGs may be the result of both increased production and inhibited secretion of renin.
我们研究了血管紧张素转换酶抑制剂（ACEI）替莫普利（Tem）对环孢素诱导的大鼠肾毒性（CsA-NT）的影响。
使用雄性Wistar大鼠。第1组（G1）仅接受介质（即橄榄油），第2组（G2）仅接受环孢素（30毫克/千克/天），第3组（G3）接受环孢素（30毫克/千克/天）和替莫普利（80微克/千克/天），第4组（G4）仅接受替莫普利（80微克/千克/天）。每组由5只动物组成。药物口服给药14天。然后，测量肾皮质血流量（RCBF）、血清肌酐（S-Cr）、血清钾（S-K）、全血环孢素（WB-CsA）、血清醛固酮（Ald）和血浆肾素活性（PRA）的浓度。还计算了肌酐清除率（CCr）。肾脏用鲍伊染色进行光镜检查，并通过图像分析系统估计肾素颗粒的大小（S-RGs）。
G2组显示RCBF降低（p < 0.01）、S-Cr升高（p < 0.01）、CCr降低（p < 0.01）、S-K升高（p < 0.05）和S-RGs升高（p < 0.01）。与G2组相比，G3组在RCBF（p < 0.01）和S-Cr（p < 0.05）方面有显著改善，但所有指标仍有显著损害（与对照组相比，p < 0.01或p < 0.05）。与G1组相比，G4组除S-K显著升高（p < 0.01，与对照组相比）外无明显变化。G3组对S-K升高有额外影响（p < 0.01，与对照组和G2组相比）。替莫普利对WB-CsA水平无显著影响。这些药物对血清Ald和PRA水平无显著改变。
这些数据与以下假设一致，即入球小动脉（AAs）的血管收缩是CsA-NT的主要机制。RGs的增加可能是肾素产生增加和分泌受抑制的结果。
