Nerve function and regeneration in diabetic rats: effects of
zd7155, an angiotensin ii at1 receptor antagonist.
Maxfield, Emily K., Alastair Love, Mary A. Cotter, and Norman E.
Cameron.
Department of Biomedical Sciences, University of Aberdeen, Aberdeen
AB9 1AS, Scotland, United Kingdom
APStracts 2:0092E, 1995.
Effects of the angiotensin II AT1 receptor antagonist, ZD7155, on
nerve function, blood flow, capillarization, oxygenation and
regenerative capacity following injury were studied in
streptozotocin-diabetic rats. Deficits in saphenous sensory and
sciatic motor conduction velocity measured after 1 or 2 mo diabetes
in anesthetized rats were prevented and corrected by ZD7155. Sciatic
resistance to hypoxic conduction failure, 71% increased by 2 mo
diabetes, was attenuated by 39% with ZD7155. Endoneurial capillary
density, unaffected by diabetes, was 34% increased with 2 mo ZD7155
treatment. Sciatic nutritive endoneurial blood flow, which was 45%
reduced by 2 mo diabetes, remained in the nondiabetic range with
ZD7155. Mean endoneurial oxygen tension was 38% reduced by diabetes,
which was attenuated by ZD7155. 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 diabetes, which was prevented by ZD7155 treatment from
diabetes induction. Thus, alterations in the renin-angiotensin system
contribute to the neurovascular etiology of nerve dysfunction in
experimental diabetes.
Received 10 February 1995; accepted in final form 21 April 1995.
APS Manuscript Number E60-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 2 May 1995.