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