Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
ACE Inhibitor or Angiotensin II Receptor Antagonist Attenuates Diabetic Neuropathy in Streptozotocin-Induced Diabetic Rats
Lawrence J. Coppey ,
Eric P. Davidson ,
Thomas W. Rinehart ,
Jill S. Gellett ,
Christine L. Oltman ,
Donald D. Lund and
Mark A. Yorek
From the Department of Internal Medicine, University of Iowa and Veterans Affairs Medical Center, Iowa City, Iowa
Address correspondence and reprint requests to Mark A. Yorek, Room 204, Building 40, Veterans Affairs Medical Center, Iowa
City, IA 52246. E-mail: mark-yorek{at}uiowa.edu
Abstract
ACE inhibition and/or blocking of the angiotensin II receptor are recognized as first-line treatment for nephropathy and cardiovascular
disease in diabetic patients. However, little information is available about the potential benefits of these drugs on diabetic
neuropathy. We examined vascular and neural activity in streptozotocin-induced diabetic rats that were treated for 12 weeks
with enalapril, an ACE inhibitor, or l -158809, an angiotensin II receptor blocker. A prevention protocol (group 1) as well as three intervention protocols (treatment
was initiated after 4, 8, or 12 weeks of diabetes [groups 2, 3, and 4, respectively]) were used. Endoneurial blood flow and
motor nerve conduction velocity (MNCV) were impaired in all groups of untreated diabetic rats. In group 1, treatment of diabetic
rats with enalapril or l -158809 partially prevented the diabetes-induced decrease in endoneurial blood flow and MNCV. In groups 2–4, intervention
with enalapril was more effective in reversing the diabetes-induced impairment in endoneurial blood flow and MNCV than l -158809. The superoxide level in the aorta and epineurial arterioles of diabetic rats was increased. Treatment of diabetic
rats with enalapril or l -158809 reduced the superoxide level in the aorta in all groups but was less effective in epineurial arterioles. Acetylcholine
and calcitonin gene–related peptide (CGRP) cause vasodilation in epineurial arterioles of the sciatic nerve, which was impaired
by diabetes. Treatment of diabetic rats (all groups) with enalapril or l -158809 completely prevented/reversed the diabetes-induced impairment in CGRP-mediated vascular relaxation. Treatment with
enalapril or l -158809 was also effective in improving impaired acetylcholine-mediated vasodilation, but the efficacy was diminished from
groups 1 to 4. These studies suggest that ACE inhibitors and/or angiotensin II receptor blockers may be effective treatments
for diabetes and vascular and neural dysfunction. However, the efficacy of these treatments may be dependent on when the treatment
is initiated.
CGRP, calcitonin gene–related peptide
MNCV, motor nerve conduction velocity
Footnotes
Accepted October 24, 2005.
Received July 11, 2005.
DIABETES