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Vascular and neural dysfunctions in obese Zucker rats: effect of AVE7688
Eric P Davidson1, Lawrence J Coppey, Travis L Kleinschmidt
1Department of Veterans Affairs Iowa City Health Care System, University of Iowa, Iowa City, IA 52246, USA.
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.
Insights
The drug AVE7688, inhibiting angiotensin converting enzyme and neutral endopeptidase, improved vascular and nerve function in metabolic syndrome rats. This treatment also reduced oxidative stress and improved pain perception.
Area of Science:
- Cardiovascular Research
- Neuroscience
- Metabolic Syndrome Research
Background:
- Metabolic syndrome is associated with vascular and nerve dysfunction.
- Obese Zucker rats serve as a model for studying metabolic syndrome.
- Age-related vascular and neural deficits occur even in normoglycemic states.
Purpose of the Study:
- To investigate the protective effects of AVE7688 on vascular and nerve functions.
- To assess AVE7688's impact on oxidative stress markers.
- To evaluate AVE7688's influence on pain perception in metabolic syndrome.
Main Methods:
- Obese Zucker rats were treated with AVE7688 for 12 weeks.
- Vascular reactivity was assessed using videomicroscopy.
- Nerve conduction velocity was measured via electrical stimulation.
- Superoxide levels and nitrotyrosine staining were quantified.
- Pain responses were evaluated using thermal and tactile stimuli.
Main Results:
- AVE7688 treatment improved vasodilation and nerve conduction velocity.
- Superoxide levels and nitrotyrosine staining in the aorta were reduced.
- Hypoalgesia and impaired tactile responses were significantly improved.
- Vascular and neural dysfunctions were ameliorated by AVE7688.
Conclusions:
- AVE7688 demonstrates significant protective effects on vascular and nerve functions.
- The drug effectively reduces oxidative stress and improves sensory deficits.
- AVE7688 offers a potential therapeutic strategy for metabolic syndrome-related complications.
