Protective effect of a novel and selective inhibitor of inducible nitric oxide synthase on experimental crescentic glomerulonephritis in WKY rats

Daisuke Ogawa, Kenichi Shikata, Mitsuhiro Matsuda, Shinichi Okada, Hitomi Kataoka, Jun Wada, Naoyuki Taniguchi, Hirofumi Makino

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2117-2121
Number of pages5
JournalNephrology Dialysis Transplantation
Volume17
Issue number12
Publication statusPublished - Dec 1 2002

Fingerprint

Inbred WKY Rats
Nitric Oxide Synthase Type II
Glomerulonephritis
Nitric Oxide Synthase
Nitric Oxide
Nephritis
Nitrites
Serum
Nitrates
Amidines
Intraperitoneal Injections
Proteinuria
Macrophages
7-chloro-3-imino-5-methyl-2-azabicyclo(4.1.0)heptane
Control Groups
Injections

Keywords

  • Crescent
  • Glomerulonephritis
  • Inducible nitric oxide synthase
  • Macrophage
  • Nitric oxide
  • ONO-1714

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Protective effect of a novel and selective inhibitor of inducible nitric oxide synthase on experimental crescentic glomerulonephritis in WKY rats. / Ogawa, Daisuke; Shikata, Kenichi; Matsuda, Mitsuhiro; Okada, Shinichi; Kataoka, Hitomi; Wada, Jun; Taniguchi, Naoyuki; Makino, Hirofumi.

In: Nephrology Dialysis Transplantation, Vol. 17, No. 12, 01.12.2002, p. 2117-2121.

Research output: Contribution to journalArticle

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AU - Taniguchi, Naoyuki

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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.

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