effect of treatment of sprague dawley rats with ave7688, enalapril, or candoxatril on diet-induced obesity治疗效果与ave7688雄性sd大鼠中,卡托普利或candoxatril食源性肥胖.pdfVIP

Hindawi Publishing Corporation Journal of Obesity Volume 2011, Article ID 686952, 9 pages doi:10.1155/2011/686952 Research Article Effect of Treatment of Sprague Dawley Rats with AVE7688, Enalapril, or Candoxatril on Diet-Induced Obesity Eric P. Davidson,1, 2 Lawrence J. Coppey,1, 2 Brian Dake,1, 2 and Mark A. Yorek1, 2 1 Veteran Aff airs Medical Center, Iowa City, IA 52246, USA 2 Department of Internal Medicine, The University of Iowa, Iowa City, IA 52242, USA Correspondence should be addressed to Mark A. Yorek, mark-yorek@ Received 21 April 2010; Accepted 29 June 2010 Academic Editor: A. Halpern Copyright © 2011 Eric P. Davidson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The objective of this study was to determine the effect of AVE7688, a drug that inhibits both angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) activity, on neural and vascular defects caused by diet induced obesity (DIO). Rats at 12 weeks of age were fed a standard or high fat diet with or without AVE7688 for 24 weeks. DIO rats had impaired glucose tolerance and developed sensory neuropathy. Vascular relaxation to acetylcholine and calcitonin gene-related peptide was decreased in epineurial arterioles of DIO rats. Rats fed a high fat diet containing AVE7688 did not become obese and vascular and sensory nerve dysfunction and impaired glucose tolerance were improved. DIO is associated with increased expression of NEP in epineurial arterioles. NEP degrades vasoactive peptides which may explain the decrease in neurovascular function in DIO. 1. Introduction