Toshihiko Kuro, Yutaka Kobayashi, Masanori Takaoka and Yasuo Matsumura*
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 4 - 20 - 1 Nasahara, Takatsuki, Osaka 569 - 1094, Japan
* To whom correspondence should be addressed.
Abstract: The effects of KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate), a novel Na+/Ca2+ exchange inhibitor, on ischemic acute renal failure (ARF) in rats were examined. ARF was induced by clamping the left renal pedicle for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function was markedly diminished in ARF rats. Pretreatment with KB-R7943 (10 mg/kg, i.v.) markedly attenuated the ARF-induced renal dysfunction. Histopathological examination of the kidney of ARF rats revealed severe renal damage, which was suppressed by KB-R7943. Activation of the reverse mode of Na+/Ca2+ exchange seems to play an important role in the pathogenesis of ARF. A selective Na+/Ca2+ exchange inhibitor may be useful in cases of ARF.
Keywords: Ischemic acute renal failure, Na+/Ca2+ exchanger, Renal function