Effect of cilostazol on experimental diabetic neuropathy in the rat.
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.
Kihara
M
M
Department of Neurology, Mayo Foundation, Rochester, Minnesota 55905, USA.
Schmelzer
J D
JD
Low
P A
PA
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D000077407:Cilostazol; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D005527:Food, Fortified; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D010525:Peripheral Nerves / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000187:drug effects / Q000503:physiopathology; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013979:Tibial Nerve / Q000187:drug effects / Q000503:physiopathology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D001786:Blood Glucose; D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D014665:Vasodilator Agents; D000077407:Cilostazol