Beraprost sodium, prostacyclin analogue, attenuates glomerular hyperfiltration and glomerular macrophage infiltration by modulating ecNOS expression in diabetic rats

Tetsuji Yamashita, Kenichi Shikata, Mitsuhiro Matsuda, Shinichi Okada, Daisuke Ogawa, Hikaru Sugimoto, Jun Wada, Hirofumi Makino

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Stable prostacyclin analogue, beraprost sodium (BPS) has recently been reported to attenuate glomerular hyperfiltration in diabetic rats, however, the mechanism has been still unknown. We previously reported that overexpression of endothelial cell nitric oxide synthase (ecNOS) in afferent arterioles and glomeruli induce inappropriate dilatation of afferent arterioles and glomerular hyperfiltration through overproduction of nitric oxide in early stage of diabetic nephropathy. In this study, we tested the hypothesis that BPS ameliorates glomerular hyperfiltration through modulating ecNOS expression in diabetic nephropathy. Furthermore, we examined the effects of BPS on the expression of intercellular adhesion molecule-1 (ICAM-1) and macrophage infiltration in diabetic glomeruli, because glomerular hyperfiltration induces the expression of ICAM-1 resulting in macrophage infiltration. Male Sprague-Dawley (SD) rats were administered continuously with BPS for 4 weeks after induction of diabetes by streptozotocin. In diabetic rats, the diameters of afferent arterioles, glomerular volume, creatinine clearance and urinary excretion of albumin and NO2/NO3 were increased as compared with non-diabetic control rats. Treatment with BPS improved these changes. The expression of ecNOS was increased in afferent arterioles and glomeruli in diabetic rats and suppressed by BPS. Prostacyclin receptor was expressed along afferent arterioles. Our results suggest that BPS attenuates glomerular hyperfiltration by modulating ecNOS expression in early stage of diabetic nephropathy. Moreover, BPS may inhibit ICAM-1-dependent infiltration of macrophages in diabetic glomeruli.

Original languageEnglish
Pages (from-to)149-161
Number of pages13
JournalDiabetes Research and Clinical Practice
Volume57
Issue number3
DOIs
Publication statusPublished - Jul 24 2002

Keywords

  • Diabetic nephropathy
  • Hyperfiltration
  • ICAM-1
  • Macrophage
  • Nitric oxide
  • Prostacyclin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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