Korean Journal of Nephrology 1991;10(3):360-371.

Nifedipine과 Captopril이 흰쥐의 Cisplatin 신독성에 미치는 영향

유병희 , 하종식 , 김구자 , 경난호

Abstract

To investigate the effect of nifedipine, a calcium channel blocker and captopril, an angiotensin I conver- ting enzyme inhibitor on cisplastin induced nephrotox- icity, we administered nifedipine, captopril and cisplatin to rats (Sprague-Dawley) and followed the changes in renal function, Na', K'-ATPase activity, electrolyte concentration, renal tissue oxygen consumption and morphological changes. Results obtained were as followings. 1) As compared with control group, a marked weight loss was observed in cisplatin administered group, and the change was not prevented by the pretreatment with nifedipine or captopril. 2) Blood pressure was lowered in cisplatin, nifedipine and captopril groups at 5th day after.administration of cisplatin. Blood pressure was recovered by preteatment with nifedipine or captopril at 8th day. 3) Urine flow increased drastically and urine os- molality following cisplatin treatment and these changes were not alliviated by the pretreatment with nifedipine or captopril. 4) In cisplatin treated animals, the urinary excretion of Na' and K were significantly reduced but the frac- tional excretions were increased. In this case, however, the nifedifine and captopril pretreatments attenuated the changes in fractional excretion. 5) In cisplatin treated animals, both the urinary excre- tion and fractional excretion of Mg" were increased drastically. These changes were not improved by nifedipine pretreatment, but were significantly attenuat- ed by captopril. 6) In cisplatin treated animals, the glomerular filtra- tion rate was reduced markedly and this was not cor- rected by pretreatment with nifedipine or captopril. 7) As compared with control group, Na', K'-ATPase activities of the outer medullary tissues were decreased remarkably following cisplatin treatment. The decre- ments were not changed by preteatment with nifedipine or captopril. 8) As compared with control group, the Na' content of the outer medullary tissue was increased and K' content was decreased in cisplatin treated animals. These changes were not affected by pretreatment with nifedipine or captopril. 9) Oxygen consumptions of renal tissues was de- creased following cisplatin treatment, and this change was not reverted by pretreatment with nifedipine ar captopril. 10) There were no changes in plasma ADH level among 4 groups, however, plasma renin activity was increased significantly following cisplatin treatment, and the increment was reduced slightly by pretreatment with nifedipine or captopril. 11) In electron microscopic study, a focal coagulative necrosis and mitochondrial swelling of proximal tubular cells were observed in cisplatin treated animals. These findings were persisted in animals pretreated with nifedipine or captopril. These results indicate 1) The cisplatin induced ne- phrotoxicity is due to an impairment of tubular reabsor- ption systems, particularly active Na' transport mecha- nism in the ascending Henles loop, an impairment ofcountercurrent multiplication system and necrosis of proximal tubule, and 2) these alteration can not be prevented by pretreatment with nifedipine or captopril.