AJP - Endocrinology and Metabolism, Vol 269, Issue 3 E530-E537, Copyright © 1995 by American Physiological Society

ARTICLES

Nerve function and regeneration in diabetic rats: effects of ZD-7155, an AT1 receptor antagonist

E. K. Maxfield, A. Love, M. A. Cotter and N. E. Cameron
Department of Biomedical Sciences, University of Aberdeen, Scotland, United Kingdom.

Effects of the angiotensin II AT1 receptor antagonist ZD-7155 on nerve function, blood flow, capillarization, oxygenation, and regenerative capacity after injury were studied in streptozocin-diabetic rats. Deficits in saphenous sensory and sciatic motor conduction velocity measured after 1 or 2 mo of diabetes in anesthetized rats were prevented and corrected by ZD-7155. Sciatic resistance to hypoxic conduction failure, which was increased by 71% by 2 mo of diabetes, was attenuated by 39% with ZD-7155. Endoneurial capillary density, which was unaffected by diabetes, was increased by 34% with 2 mo of ZD-7155 treatment. Sciatic nutritive endoneurial blood flow, which was reduced by 45% by 2 mo of diabetes, remained in the nondiabetic range with ZD-7155. Mean endoneurial O2 tension was reduced 38% by diabetes, which was attenuated by ZD-7155. Punctate freeze damage of sciatic nerve caused complete fiber degeneration. Fourteen days postlesion, there was a 26% deficit in myelinated fiber regeneration distance after 2 mo of diabetes, which was prevented by ZD-7155 treatment from diabetes induction. Thus alterations in the renin-angiotensin system contribute to the neurovascular etiology of nerve dysfunction in experimental diabetes.

This article has been cited by other articles:

				J. M. Kennedy and D. W. Zochodne The regenerative deficit of peripheral nerves in experimental diabetes: its extent, timing and possible mechanisms Brain, October 1, 2000; 123(10): 2118 - 2129. [Abstract] [Full Text] [PDF]