Effect of Inhibition of Angiotensin-Converting Enzyme and/or Neutral Endopeptidase on Neuropathy in High-Fat-Fed C57Bl/6J Mice

Lawrence Coppey; Bao Lu; Craig Gerard; Mark A Yorek

doi:10.1155/2012/326806

Back

Effect of Inhibition of Angiotensin-Converting Enzyme and/or Neutral Endopeptidase on Neuropathy in High-Fat-Fed C57Bl/6J Mice

Journal article

Open access

Peer reviewed

Effect of Inhibition of Angiotensin-Converting Enzyme and/or Neutral Endopeptidase on Neuropathy in High-Fat-Fed C57Bl/6J Mice

Lawrence Coppey, Bao Lu, Craig Gerard and Mark A Yorek

Journal of obesity, Vol.2012, 326806

2012

DOI: 10.1155/2012/326806

PMCID: PMC3465928

PMID: 23056927

Files and links (1)

url

https://doi.org/10.1155/2012/326806View

Published (Version of record) Open Access

Abstract

We have demonstrated that treating diet-induced obese (DIO) mice with the vasopeptidase inhibitor ilepatril improved neural function. Vasopeptidase inhibitors block angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) activity. We propose that increased activity of ACE and NEP contributes to pathophysiology of DIO. To address this issue C57Bl/6J mice or mice deficient in NEP were fed a high-fat diet and treated with ilepatril, enalapril, ACE inhibitor, or candoxatril, NEP inhibitor, using both prevention and intervention protocols. Endpoints included glucose utilization and neural function determination. In the prevention study glucose tolerance was impaired in DIO C57Bl/6J mice and improved with ilepatril or enalapril. Sensory nerve conduction velocity, thermal nociception, and intraepidermal nerve fiber density were impaired in DIO C57Bl/6J mice and improved with ilepatril or candoxatril. In the intervention study only enalapril improved glucose tolerance. Sensory nerve conduction velocity and intraepidermal nerve fiber density were improved by all three treatments, whereas thermal nociception was improved by ilepatril or candoxatril. In NEP-deficient mice DIO impaired glucose utilization and this was improved with enalapril. Nerve function was not impaired by DIO in NEP-deficient mice. These studies suggest that ACE and NEP play a role in pathophysiology associated with DIO.

Details

Title: Subtitle: Effect of Inhibition of Angiotensin-Converting Enzyme and/or Neutral Endopeptidase on Neuropathy in High-Fat-Fed C57Bl/6J Mice
Creators: Lawrence Coppey - Department of Veterans Affairs Iowa City Health Care System, Iowa City, IA 52246, USA, Department of Internal Medicine, University of Iowa, Iowa City, IA 52246, USA
Bao Lu - Ina Sue Perlmutter Laboratory, Children’s Hospital, Department of Pediatrics and Medicine, Harvard Medical School, Boston, MA 02115, USA
Craig Gerard - Ina Sue Perlmutter Laboratory, Children’s Hospital, Department of Pediatrics and Medicine, Harvard Medical School, Boston, MA 02115, USA
Mark A Yorek - Department of Veterans Affairs Iowa City Health Care System, Iowa City, IA 52246, USA, Department of Internal Medicine, University of Iowa, Iowa City, IA 52246, USA
Resource Type: Journal article
Publication Details: Journal of obesity, Vol.2012, 326806
DOI: 10.1155/2012/326806
PMID: 23056927
PMCID: PMC3465928
NLM abbreviation: J Obes
ISSN: 2090-0708
eISSN: 2090-0716
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: DK073990, BX001680
Language: English
Date published: 2012
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094711202771

Metrics

18 Record Views

15 Times Cited - Web of Science