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 language | English (US) |
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Pages (from-to) | 914-918 |
Number of pages | 5 |
Journal | Diabetologia |
Volume | 38 |
Issue number | 8 |
DOIs | |
State | Published - Aug 1995 |
Keywords
- Diabetic neuropathy
- cilostazol
- nerve blood flow
- sciatic nerve
- vasodilator
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism