Effect of cilostazol on experimental diabetic neuropathy in the rat

M. Kihara, J. D. Schmelzer, P. A. Low

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Two proposed mechanisms of diabetic neuropathy are microvascular ischaemia and a reduction in Na,K-ATPase activity. We evaluated the effect of cilostazol, a drug that is both a potent phosphodiesterase inhibitor that normalizes nerve Na,K-AT-Pase and a vasodilator, on nerve blood flow (NBF) to determine whether it would improve experimental diabetic neuropathy. We examined whether epineurally applied cilostazol acted as a vasodilator on the peripheral nerve of normal and diabetic rats, and whether feeding the rats a cilostazol-supplemented diet could improve diabetic neuropathy. Cilostazol increased nerve blood flow (NBF) in a dose-dependent fashion with an EC50 of 10-5.74 mol/l. Cilostazol also normalized NBF in experimental diabetic neuropathy with a 10-4 mol/l local application on the sciatic nerve. In diabetic neuropathy, a cilostazol-supplemented diet improved both NBF and nerve conduction in a dose- and time-dependent fashion. Potential mechanisms of action of cilostazol on the nerve include its effect on NBF, Na, K-ATPase, and restoration of the thromboxane:prostacyclin ratio. Cilostazol may have potential in the treatment of diabetic neuropathy.

Original languageEnglish (US)
Pages (from-to)914-918
Number of pages5
JournalDiabetologia
Volume38
Issue number8
DOIs
StatePublished - Aug 1 1995

Keywords

  • Diabetic neuropathy
  • cilostazol
  • nerve blood flow
  • sciatic nerve
  • vasodilator

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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