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Attenuation of vascular/neural dysfunction in Zucker rats treated with enalapril or rosuvastatin
Christine L Oltman1, Eric P Davidson, Lawrence J Coppey
1Department of Veteran Affairs, Iowa City, Iowa, USA.
Objective:
Obese Zucker rats, animal model for the metabolic syndrome, develop a diabetes-like neuropathy that is independent of hyperglycemia. The purpose of this study was to determine whether drugs used to treat cardiovascular dysfunction in metabolic syndrome also protect nerve function.
Methods And Procedures:
Obese Zucker rats at 20 weeks of age were treated for 12 weeks with enalapril or rosuvastatin. Lean rats were used as controls. Vasodilation in epineurial arterioles was measured by videomicroscopy. Endoneurial blood flow (EBF) was measured by hydrogen clearance and nerve conduction velocity was measured following electrical stimulation of motor or sensory nerves.
Results:
Enalapril treatment decreased serum angiotensin-converting enzyme (ACE) activity and both drugs reduced serum cholesterol levels. In obese Zucker rats at 32 weeks of age superoxide levels were elevated in the aortas and epineurial arterioles, which were reduced by treatment with either drug. Nitrotyrosine levels were increased in epineurial arterioles and reduced with enalapril treatment. EBF was decreased and corrected by treatment with either drug. Motor nerve conduction velocity was decreased and significantly improved with enalapril treatment. Obese Zucker rats were hypoalgesic in response to a thermal stimulus and this was significantly improved with either treatment. Treatment with either enalapril or rosuvastatin significantly reversed the decrease in acetylcholine-mediated vascular relaxation of epineurial arterioles in obese Zucker rats.
Discussion:
Even though obese Zucker rats have normal glycemia vascular and neural dysfunctions develop with age and can be improved by treatment with either enalapril or rosuvastatin.
Insights
Cardiovascular drugs enalapril and rosuvastatin improved nerve function and vascular dysfunction in obese Zucker rats with metabolic syndrome, independent of blood sugar levels.
Area of Science:
- Neuroscience
- Cardiovascular Science
- Metabolic Syndrome Research
Background:
- Obese Zucker rats, a model for metabolic syndrome, develop neuropathy independent of hyperglycemia.
- Cardiovascular dysfunction is a common comorbidity in metabolic syndrome.
Purpose of the Study:
- To investigate if cardiovascular drugs (enalapril, rosuvastatin) protect nerve function in obese Zucker rats.
- To assess the impact of these drugs on vascular and neural deficits associated with metabolic syndrome.
Main Methods:
- Obese Zucker rats were treated with enalapril or rosuvastatin for 12 weeks.
- Measurements included epineurial arteriole vasodilation, endoneurial blood flow (EBF), nerve conduction velocity, and thermal hypoalgesia response.
Main Results:
- Both drugs reduced cholesterol; enalapril reduced ACE activity. Superoxide levels decreased with both treatments.
- Enalapril and rosuvastatin improved EBF and vascular relaxation. Enalapril significantly improved motor nerve conduction velocity.
- Both treatments significantly improved hypoalgesia in obese Zucker rats.
Conclusions:
- Vascular and neural dysfunctions manifest in obese Zucker rats with normal glycemia.
- Enalapril and rosuvastatin treatments effectively improved these age-related vascular and neural deficits.
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