McAuley F T, Whiting P H, Thomson A W, Simpson J G
Biochem Pharmacol. 1987 Mar 1;36(5):699-703. doi: 10.1016/0006-2952(87)90721-0.
Adult Sprague-Dawley rats treated daily for 14 days with 50 mg/kg cyclosporin A (CsA) exhibited nephrotoxicity, characterized by reduced glomerular filtration rate, decreased urinary sodium and potassium flow, tubular enzymuria and proximal tubular structural damage. Elevations in plasma renin activity (PRA) were observed on day 4, but returned to normal within 7 days. Co-treatment of animals for the 14 day period with enalapril (8 mg/kg/day), a potent inhibitor of angiotensin converting enzyme (ACE), or spironolactone (25 mg/kg/day), the distal tubular antagonist of aldosterone, reduced the nephrotoxicity, although PRA remained elevated. Neither enalapril nor spironolactone affected circulating CsA levels. These data suggest that the action of aldosterone on the distal tubule may be important in the pathogenesis of CsA nephrotoxicity.
成年Sprague-Dawley大鼠每天用50毫克/千克环孢素A（CsA）处理14天，表现出肾毒性，其特征为肾小球滤过率降低、尿钠和钾流量减少、肾小管酶尿以及近端肾小管结构损伤。在第4天观察到血浆肾素活性（PRA）升高，但在7天内恢复正常。在14天期间，用血管紧张素转换酶（ACE）的强效抑制剂依那普利（8毫克/千克/天）或醛固酮的远端肾小管拮抗剂螺内酯（25毫克/千克/天）对动物进行联合处理，可降低肾毒性，尽管PRA仍保持升高。依那普利和螺内酯均未影响循环中的CsA水平。这些数据表明，醛固酮对远端肾小管的作用可能在CsA肾毒性的发病机制中起重要作用。
