Effects of nimodipine on sciatic nerve blood flow and vasa nervorum responsiveness in the diabetic rat.
Evidence is accumulating that impairment of nerve blood flow is a key factor in the pathogenesis of diabetic neuropathy. Nimodipine, a 1,4-dihydropyridine type Ca2+ channel antagonist, has been shown to ameliorate an existing neuropathy in the streptozotocin-induced diabetic rat. In the present study the effect of diabetes mellitus itself and the effect of chronic nimodipine treatment on the sciatic nerve blood flow of streptozotocin-induced diabetic rats were investigated. Nerve blood flow was assessed using laser-Doppler flowmetry. Nerve blood flow gradually decreased during the first 10 weeks of diabetes mellitus and remained relatively stable thereafter. Intervention with nimodipine significantly improved the flow deficit observed in the diabetic rats. Vasa nervorum adrenergic responsiveness was also investigated. Diabetic rats showed a postsynaptic adrenergic hyporesponsiveness. Treatment with nimodipine restored the reduced presynaptic responsiveness independent of the postsynaptic adrenergic hyporesponsiveness. It was concluded that, in addition to direct neuroprotective effects, nimodipine exerts beneficial effects on disturbed nerve blood flow and on reduced presynaptic adrenergic responsiveness of the vasa nervorum in experimental diabetic neuropathy.
Kappelle
A C
AC
Department of Medical Pharmacology, Rudolf Magnus Institute, University of Utrecht, Netherlands.
Biessels
G J
GJ
Van Buren
T
T
Erkelens
D W
DW
De Wildt
D J
DJ
Gispen
W H
WH
D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000098:blood supply* / Q000187:drug effects; D014650:Vasa Nervorum / Q000187:drug effects* / Q000502:physiology
D001786:Blood Glucose; D010656:Phenylephrine; D009553:Nimodipine