Using Na+/Ca2+ exchanger (NCX1)-deficient mice, the pathophysiological role of Ca2+ overload via the reverse mode of the Na+/Ca2+ exchanger in ischaemia/reperfusion-induced renal injury was investigated. Since NCX1-/- homozygous mice die of heart failure before birth, we utilized NCX1+/- heterozygous mice. The ischaemia/reperfusion-induced renal dysfunction in heterozygous mice were significantly attenuated compared with cases in wild-type mice. Also, histological renal damage such as tubular necrosis and proteinaceous casts in tubuli in heterozygous mice were much less than that in wild-type mice. Ca2+ deposition in necrotic tubular epithelium was observed more markedly in wild-type than in heterozygous mice. The increase in renal endothelin-1 (ET-1) content was significantly greater in wild-type than in heterozygous mice, and this reflected the difference in immunohistochemical ET-1 localization in necrotic tubular epithelium. We conclude that Ca2+ overload via the reverse-mode of Na+/Ca2+ exchange, followed by renal ET-1 overproduction, plays an important role in the pathogenesis of ischaemia/reperfusion-induced acute renal failure.
Pathophysiological roles of Ca2+ overload via the Na+/Ca2+ exchanger and endothelin-1 overproduction in ischaemia/reperfusion-induced acute renal failure
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Yasuo MATSUMURA, Junji YAMASHITA, Satomi KITA, Takahiro IWAMOTO, Masaya OGATA, Masanori TAKAOKA, Koji WAKIMOTO, Munekazu SHIGEKAWA, Issei KOMURO; Pathophysiological roles of Ca2+ overload via the Na+/Ca2+ exchanger and endothelin-1 overproduction in ischaemia/reperfusion-induced acute renal failure. Clin Sci (Lond) 1 September 2002; 103 (s2002): 389S–392S. doi: https://doi.org/10.1042/CS103S389S
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