Summary
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.
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Abbreviations
- EDN:
-
Experimental diabetic neuropathy
- NBF:
-
nerve blood flow
- STZ:
-
streptozotocin
- NRC:
-
control rats receiving normal diet
- NRH:
-
control rats receiving a high (0.1%) cilostazol diet
- CSH:
-
STZ rats receiving high (0.1%) cilostazol diet
- CSL:
-
STZ rats receiving low (0.03%) cilostazol diet
- CV:
-
conduction velocity
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Kihara, M., Schmelzer, J.D. & Low, P.A. Effect of cilostazol on experimental diabetic neuropathy in the rat. Diabetologia 38, 914–918 (1995). https://doi.org/10.1007/BF00400579
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DOI: https://doi.org/10.1007/BF00400579