Journal article
Treatment of Zucker diabetic fatty rats with AVE7688 improves vascular and neural dysfunction
Diabetes, obesity & metabolism, Vol.11(3), pp.223-233
Received 16 March 2008; accepted 2 May 2008
03/2009
DOI: 10.1111/j.1463-1326.2008.00924.x
PMCID: PMC2667677
PMID: 18564175
Abstract
Aim: Vasopeptidase inhibitors are drugs that inhibit angiotensin-converting enzyme and neutral endopeptidase (NEP). The latter is a protease that degrades vasoactive peptides and is increased in diabetes. We have previously shown that treating streptozotocin-induced diabetic rats, an animal model of type 1 diabetes, with AVE7688, a vasopeptidase inhibitor, improves neurovascular and neural function. In this study, we determined the effect of treating Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes, with AVE7688 on vascular and neural function.
Methods: ZDF rats at 12 weeks of age were treated for 12 weeks with AVE7688 (500 mg/kg diet). Afterwards, vascular reactivity of epineurial arterioles of the sciatic nerve and nerve conduction velocity and blood flow was determined.
Results: Vascular and neural function was significantly impaired in ZDF rats compared with age-matched lean (control) rats. Treating ZDF rats with AVE7688 improved vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles. Motor and sensory nerve conduction velocity, endoneurial blood flow and thermal nociception end-points were also improved by treatment compared with untreated ZDF rats. Superoxide and expression of NEP were increased in epineurial arterioles from ZDF rats and attenuated by treatment with AVE7688.
Conclusions: AVE7688 is an effective treatment for microvascular and neural disease in ZDF rats. Thus, vasopeptidase inhibitors may be an effective treatment for diabetic microvascular and neural complication in type 2 diabetes.
Details
- Title: Subtitle
- Treatment of Zucker diabetic fatty rats with AVE7688 improves vascular and neural dysfunction
- Creators
- C. L Oltman - Veteran Affairs Medical Center, Iowa City, IA, USAE. P Davidson - Veteran Affairs Medical Center, Iowa City, IA, USAL. J Coppey - Veteran Affairs Medical Center, Iowa City, IA, USAT. L Kleinschmidt - Veteran Affairs Medical Center, Iowa City, IA, USAM. A Yorek - Veteran Affairs Medical Center, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Diabetes, obesity & metabolism, Vol.11(3), pp.223-233
- Edition
- Received 16 March 2008; accepted 2 May 2008
- DOI
- 10.1111/j.1463-1326.2008.00924.x
- PMID
- 18564175
- PMCID
- PMC2667677
- NLM abbreviation
- Diabetes Obes Metab
- ISSN
- 1462-8902
- eISSN
- 1463-1326
- Publisher
- Wiley
- Number of pages
- 11
- Language
- English
- Date published
- 03/2009
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094761602771
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