Nerve function and regeneration in diabetic rats: effects of ZD-7155, an AT1 receptor antagonist.
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.
Maxfield
E K
EK
Department of Biomedical Sciences, University of Aberdeen, Scotland, United Kingdom.
Love
A
A
Cotter
M A
MA
Cameron
N E
NE
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002196:Capillaries / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects; D009420:Nervous System / Q000098:blood supply / Q000503:physiopathology*; D009431:Neural Conduction / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012501:Saphenous Vein / Q000294:innervation; D012584:Sciatic Nerve / Q000503:physiopathology; D012677:Sensation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D009287:Naphthyridines; D014665:Vasodilator Agents; C095905:ZD 7155; D010100:Oxygen