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Beneficial effect of the Ca 2+ antagonist, nimodipine, on existing diabetic neuropathy in the BB/Wor rat
Author(s) -
Kappelle A.C.,
Biessels G.,
Bravenboer B.,
Buren T.,
Traber J.,
Wildt D.J.,
Gispen W.H.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14821.x
Subject(s) - medicine , nimodipine , nerve conduction velocity , diabetic neuropathy , phenylephrine , diabetes mellitus , anesthesia , antagonist , endocrinology , sciatic nerve , calcium , blood pressure , receptor
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 Ca 2+ 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.