TY - JOUR
T1 - Protective effect of a novel and selective inhibitor of inducible nitric oxide synthase on experimental crescentic glomerulonephritis in WKY rats
AU - Ogawa, Daisuke
AU - Shikata, Kenichi
AU - Matsuda, Mitsuhiro
AU - Okada, Shinichi
AU - Usui, Hitomi
AU - Wada, Jun
AU - Taniguchi, Naoyuki
AU - Makino, Hirofumi
N1 - Funding Information:
Acknowledgements. A portion of this study was supported by a Grant-in-Aid for Scientific Research (C) (11671036 to K.S.) from the Ministry of Education, Science, Culture, Sports and Technology of Japan. We thank Ms Atsuko Yuasa (Okayama Central Hospital, Okayama, Japan) for excellent technical assistance.
PY - 2002/12/1
Y1 - 2002/12/1
N2 - Background. Nitric oxide (NO) plays important roles in a variety of pathophysiological processes. It has been reported that inducible NO synthase (iNOS) is upregulated in the glomeruli of patients with glomerulonephritis, although there has been no direct evidence that NO generated by iNOS contributes to the progression of glomerulonephritis. ONO-1714, a novel cyclic amidine analog, is a selective inhibitor of iNOS. To elucidate the role of iNOS in the pathogenesis of experimental crescentic glomerulonephritis, we examined the effect of ONO-1714 given to rats with nephrotoxic serum (NTS) nephritis. Methods. We induced NTS nephritis in Wistar-Kyoto (WKY) rats. These rats were given ONO-1714 or physiological saline intraperitoneally for 14 days using an osmotic pump after intraperitoneal injection with NTS. Results. Glomerular expression of iNOS and urinary excretion of NO metabolites (nitrite/nitrate) were increased in rats after injection of NTS. As compared with the control group, ONO-1714 significantly reduced proteinuria, crescent formation, glomerular infiltration of macrophages and urinary excretion of nitrite/nitrate. Conclusion. The present results suggest that NO radicals generated by iNOS contribute to the progression of experimental crescentic glomerulonephritis in WKY rats. The selective iNOS inhibitor ONO-1714 may be beneficial for the treatment of crescentic glomerulonephritis.
AB - Background. Nitric oxide (NO) plays important roles in a variety of pathophysiological processes. It has been reported that inducible NO synthase (iNOS) is upregulated in the glomeruli of patients with glomerulonephritis, although there has been no direct evidence that NO generated by iNOS contributes to the progression of glomerulonephritis. ONO-1714, a novel cyclic amidine analog, is a selective inhibitor of iNOS. To elucidate the role of iNOS in the pathogenesis of experimental crescentic glomerulonephritis, we examined the effect of ONO-1714 given to rats with nephrotoxic serum (NTS) nephritis. Methods. We induced NTS nephritis in Wistar-Kyoto (WKY) rats. These rats were given ONO-1714 or physiological saline intraperitoneally for 14 days using an osmotic pump after intraperitoneal injection with NTS. Results. Glomerular expression of iNOS and urinary excretion of NO metabolites (nitrite/nitrate) were increased in rats after injection of NTS. As compared with the control group, ONO-1714 significantly reduced proteinuria, crescent formation, glomerular infiltration of macrophages and urinary excretion of nitrite/nitrate. Conclusion. The present results suggest that NO radicals generated by iNOS contribute to the progression of experimental crescentic glomerulonephritis in WKY rats. The selective iNOS inhibitor ONO-1714 may be beneficial for the treatment of crescentic glomerulonephritis.
KW - Crescent
KW - Glomerulonephritis
KW - Inducible nitric oxide synthase
KW - Macrophage
KW - Nitric oxide
KW - ONO-1714
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U2 - 10.1093/ndt/17.12.2117
DO - 10.1093/ndt/17.12.2117
M3 - Article
C2 - 12454221
AN - SCOPUS:0036900792
VL - 17
SP - 2117
EP - 2121
JO - Proceedings of the European Dialysis and Transplant Association - European Renal Association. European Dialysis and Transplant Association - European Renal Association. Congress
JF - Proceedings of the European Dialysis and Transplant Association - European Renal Association. European Dialysis and Transplant Association - European Renal Association. Congress
SN - 0931-0509
IS - 12
ER -