Epalrestat prevents the decrease in gastric mucosal blood flow and protects the gastric mucosa in streptozotocin diabetic rats

Hitoshi Suzuki, Toru Shimosegawa, Shuichi Ohara, Takayoshi Toyota

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

We have recently reported that steadystate gastric mucosal blood flow (GMBF) is decreased in streptozotocin (STZ) diabetic rats, and that their GMBF response to hum-stress is impaired, probably via a nitric oxide (NO)-mediated mechanism. Accordingly, this study was designed to investigate the relation of aldose reductase (AR) and NO synthase to the regulation of GMBF during chronic hyperglycemia. STZ rats were treated with or without chronic oral administration of an AR inhibitor, epalrestat (EPA) and/or an NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME). GMBF was measured by laser-Doppler velocimetry (LDV). In the STZ rats, GMBF after a 24-h fasting period was decreased significantly 4 weeks after the onset of diabetes and this was accompanied by an increase in the gastric ulcer index (UT) (a measure of the length of gastric erosions and ulcers). Chronic oral administration of EPA to the STZ rats dose-dependently inhibited the increased UI and the decreased GMBF after the fasting stress, whereas chronic oral administration of L-NAME further increased the UT and further decreased the GMBF. EPA administered in combination with L-NAME to the STZ rats reduced the effects of L-NAME, but the effects did not reach significance. These results suggest that EPA protects the gastric mucosa of diabetic rats, by preventing the decrease in GMBF that is, at least in part, caused by NO-related mechanisms.

Original languageEnglish
Pages (from-to)172-177
Number of pages6
JournalJournal of gastroenterology
Volume34
Issue number2
DOIs
Publication statusPublished - 1999 Apr 1

Keywords

  • Epalrestat
  • Gastric mucosal blood flow
  • Gastric mucosal injury
  • Nitric oxide
  • Streptozotocin diabetic rats

ASJC Scopus subject areas

  • Gastroenterology

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