Vascular and neural dysfunctions in obese Zucker rats: effect of AVE7688.
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.
Davidson
Eric P
EP
Department of Veterans Affairs Iowa City Health Care System, University of Iowa, Iowa City, IA 52246, USA.
Coppey
Lawrence J
LJ
Kleinschmidt
Travis L
TL
Oltman
Christine L
CL
Yorek
Mark A
MA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000503:physiopathology*; D015260:Neprilysin / Q000037:antagonists & inhibitors; D009420:Nervous System / Q000187:drug effects* / Q000503:physiopathology*; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D009431:Neural Conduction / Q000187:drug effects; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker; D014652:Vascular Diseases / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects
C479877:AVE 7688; D000806:Angiotensin-Converting Enzyme Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D015260:Neprilysin