Attenuation of vascular/neural dysfunction in Zucker rats treated with enalapril or rosuvastatin

Christine L Oltman; Eric P Davidson; Lawrence J Coppey; Travis L Kleinschmidt; Donald D Lund; Mark A Yorek

doi:10.1038/oby.2007.19

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Attenuation of vascular/neural dysfunction in Zucker rats treated with enalapril or rosuvastatin

Journal article

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Attenuation of vascular/neural dysfunction in Zucker rats treated with enalapril or rosuvastatin

Christine L Oltman, Eric P Davidson, Lawrence J Coppey, Travis L Kleinschmidt, Donald D Lund and Mark A Yorek

Obesity (Silver Spring, Md.), Vol.16(1), pp.82-89

01/2008

DOI: 10.1038/oby.2007.19

PMID: 18223617

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Abstract

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. 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. 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. 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.

Arterioles - physiology

Sciatic Nerve - physiology

Nociceptors - physiology

Male

Peripheral Nerves - drug effects

Sciatic Nerve - blood supply

Tyrosine - analogs & derivatives

Fluorobenzenes - pharmacology

Cardiovascular System - physiopathology

Metabolic Syndrome - physiopathology

Superoxides - metabolism

Angiotensin-Converting Enzyme Inhibitors - pharmacology

Neural Conduction - drug effects

Motor Neurons - drug effects

Disease Models, Animal

Neurons, Afferent - drug effects

Motor Neurons - physiology

Vasodilator Agents - pharmacology

Acetylcholine - pharmacology

Rats

Rosuvastatin Calcium

Neural Conduction - physiology

Obesity - physiopathology

Cardiovascular System - drug effects

Pyrimidines - pharmacology

Sulfonamides - pharmacology

Arterioles - drug effects

Neurons, Afferent - physiology

Peripheral Nerves - physiopathology

Rats, Zucker

Tyrosine - metabolism

Animals

Enalapril - pharmacology

Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology

Nociceptors - drug effects

Details

Title: Subtitle: Attenuation of vascular/neural dysfunction in Zucker rats treated with enalapril or rosuvastatin
Creators: Christine L Oltman - Department of Veteran Affairs, Iowa City, Iowa, USA
Eric P Davidson
Lawrence J Coppey
Travis L Kleinschmidt
Donald D Lund
Mark A Yorek
Resource Type: Journal article
Publication Details: Obesity (Silver Spring, Md.), Vol.16(1), pp.82-89
DOI: 10.1038/oby.2007.19
PMID: 18223617
NLM abbreviation: Obesity (Silver Spring)
ISSN: 1930-7381
eISSN: 1930-739X
Grant note: DK073990 / NIDDK NIH HHS R01 DK073990 / NIDDK NIH HHS
Language: English
Date published: 01/2008
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094580502771

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