Summary
Abnormal vascular endothelium function may contribute to the reduced nerve perfusion implicated in the aetiology of neuropathy in diabetes mellitus. The aim was to test the hypothesis that a powerful vasoconstrictor, endothelin-1, could be involved in nerve dysfunction in streptozotocin-diabetic rats. After 6 weeks of untreated diabetes, rats were implanted with osmotic minipumps which continuously delivered the endothelin-1 antagonist, BQ-123, to the circulation via a jugular vein cannula. Sciatic motor conduction velocity, monitored serially, was increased after 4 days, treatment (p=0.028), and reached asymptote by 9–11 days (p=0.0001), when the degree of amelioration was approximately 60% of the initial diabetic deficit. Treatment of non-diabetic rats for 13 days with BQ-123 had no significant effect on motor conduction velocity. Sensory saphenous nerve conduction velocity was measured acutely after 20 days, BQ-123 treatment. The amelioration of a sensory deficit was approximately 80% (p<0.001); the resultant conduction velocity value was not significantly different from that of a non-diabetic control group. After 20 days, treatment, sciatic nutritive endoneurial blood flow was measured by microelectrode polarography and hydrogen clearance. A 48% deficit with untreated diabetes (p<0.001) was 64% ameliorated by BQ-123 treatment (p<0.001). In non-diabetic rats, BQ-123 treatment had no effect on blood flow. We conclude that endothelin-1 does not seem to be involved in the control of nerve blood flow in non-diabetic rats; however, it makes a major contribution to the perfusion deficit in experimental diabetes. This has deleterious consequences for nerve conduction, and it is possible that endothelin-1 receptor blockade may have therapeutic potential in diabetic patients.
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Abbreviations
- ED50 :
-
50% effective dose
- EMG:
-
electromyogram
- ET:
-
endothelin-1
- NCV:
-
nerve conduction velocity
- NO:
-
nitric oxide
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Cameron, N.E., Dines, K.C. & Cotter, M.A. The potential contribution of endothelin-1 to neurovascular abnormalities in streptozotocin-diabetic rats. Diabetologia 37, 1209–1215 (1994). https://doi.org/10.1007/BF00399794
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DOI: https://doi.org/10.1007/BF00399794