title: Attenuation of vascular/neural dysfunction in Zucker rats treated with enalapril or rosuvastatin.
abstract: 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
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Veteran Affairs, Iowa City, Iowa, USA.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Oltman
authors.forename: Eric P
authors.initials: EP
authors.lastname: Davidson
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Coppey
authors.forename: Travis L
authors.initials: TL
authors.lastname: Kleinschmidt
authors.forename: Donald D
authors.initials: DD
authors.lastname: Lund
authors.forename: Mark A
authors.initials: MA
authors.lastname: Yorek
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology*; D005464:Fluorobenzenes / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D009765:Obesity / Q000503:physiopathology*; D010525:Peripheral Nerves / Q000187:drug effects / Q000503:physiopathology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D000068718:Rosuvastatin Calcium; D012584:Sciatic Nerve / Q000098:blood supply / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D014665:Vasodilator Agents; D013481:Superoxides; C002744:3-nitrotyrosine; D014443:Tyrosine; D004656:Enalapril; D000068718:Rosuvastatin Calcium; D000109:Acetylcholine