Beneficial effect of the Ca2+ antagonist, nimodipine, on existing diabetic neuropathy in the BB/Wor rat

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Abstract
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.