Beneficial effect of the Ca2+ antagonist, nimodipine, on existing diabetic neuropathy in the BB/Wor rat.
1. Neuropathy is a frequently diagnosed complication of diabetes mellitus. Effective pharmacotherapy is not available. 2. The spontaneously diabetic BB/Wor rats develop secondary complications like neuropathy as do human diabetic patients. 3. BB/Wor rats treated with insulin via a subcutaneous implant show a significant impairment of sensory and motor nerve conduction velocity 6 weeks after the onset of diabetes mellitus. 4. Intraperitoneal treatment of diabetic BB/Wor rats with the Ca2+ antagonist, nimodipine (20 mg kg-1), from week 6 onwards every 48 h for a period of 6 weeks resulted in a significant increase of sensory and motor nerve conduction velocity. 5. Twelve weeks after the onset of diabetes mellitus BB/Wor rats show a 40% impairment of sciatic nerve blood flow as compared to the non-diabetic age-matched controls. Treatment with nimodipine (20 mg kg-1) from week 6 onwards significantly increased the sciatic nerve blood flow as compared to placebo-treated diabetic BB/Wor rats. 6. The adrenergic responsiveness of the vasa nervorum of the sciatic nerve to tyramine and phenylephrine was investigated as a parameter for autonomic neuropathy. 7. The fact that nimodipine treatment restored the reduced response to tyramine independently of the reduced postsynaptic phenylephrine responsiveness indicates that nimodipine improves adrenergic responsiveness mainly at the presynaptic level.
Kappelle
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Department of Medical Pharmacology, Rudolf Magnus Institute, University of Utrecht, The Netherlands.
Biessels
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G
Bravenboer
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B
van Buren
T
T
Traber
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J
de Wildt
D J
DJ
Gispen
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D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology*; D017933:Peripheral Nervous System / Q000187:drug effects / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011913:Rats, Inbred BB; D012584:Sciatic Nerve / Q000098:blood supply / Q000187:drug effects; D014439:Tyramine / Q000494:pharmacology
D001786:Blood Glucose; D010656:Phenylephrine; D009553:Nimodipine; D014439:Tyramine