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Experimental Diabetes Research
Volume 2009 (2009), Article ID 912327, 8 pages
http://dx.doi.org/10.1155/2009/912327
Research Article

Vascular and Neural Dysfunctions in Obese Zucker Rats: Effect of AVE7688

1Department of Veterans Affairs Iowa City Health Care System, University of Iowa, Iowa City, IA 52246, USA
2Department of Internal Medicine, University of Iowa, Iowa City, IA 52246, USA

Received 3 February 2009; Accepted 12 May 2009

Academic Editor: Soroku Yagihashi

Copyright © 2009 Eric P. Davidson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The purpose of this study was to determine whether AVE7688 a drug that inhibits both angiotensin converting enzyme and neutral endopeptidase activity protects vascular and nerve functions in an animal model of metabolic syndrome. Obese Zucker rats at 20 weeks of age were treated for 12 weeks with AVE7688. Vasodilation in epineurial arterioles was measured by videomicroscopy and nerve conduction velocity was measured following electrical stimulation. Treatment with AVE7688 improved vascular relaxation in response to acetylcholine and motor and sensory nerve conduction velocity. In obese Zucker rats superoxide levels and nitrotyrosine staining were elevated in the aorta and treatment corrected both conditions. Obese Zucker rats were hypoalgesic in response to a thermal stimulus and demonstrated signs of impaired tactile response and both conditions were significantly improved with treatment. Even though obese Zucker rats are normoglycemic vascular and neural dysfunctions develop with age and can be improved by treatment with AVE7688.