Effect of treatment of high fat fed/low dose streptozotocin-diabetic rats with Ilepatril on vascular and neural complications

Eric P Davidson; Lawrence J Coppey; Amey Holmes; Brian Dake; Mark A Yorek

doi:10.1016/j.ejphar.2011.07.016

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Effect of treatment of high fat fed/low dose streptozotocin-diabetic rats with Ilepatril on vascular and neural complications

Journal article

Peer reviewed

Effect of treatment of high fat fed/low dose streptozotocin-diabetic rats with Ilepatril on vascular and neural complications

Eric P Davidson, Lawrence J Coppey, Amey Holmes, Brian Dake and Mark A Yorek

European journal of pharmacology, Vol.668(3), pp.497-506

2011

DOI: 10.1016/j.ejphar.2011.07.016

PMCID: PMC3185159

PMID: 21816138

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https://www.ncbi.nlm.nih.gov/pmc/articles/3185159View

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Abstract

We have previously shown that treating streptozotocin-induced diabetic rats, an animal model of type 1 diabetes, with Ilepatril (an inhibitor of neutral endopeptidase and angiotensin converting enzyme (ACE)) improves vascular and neural functions. In this study we sought to determine the effect of Ilepatril treatment of high fat fed/low dose streptozotocin-diabetic rats, a model for type 2 diabetes, on vascular and neural complications. Following 8 weeks on a high fat diet rats were treated with 30 mg/kg streptozotocin (i.p.) and after 4 additional weeks a group of these rats was treated for 12 weeks with Ilepatril followed by analysis of neural and vascular functions. Included in these studies were age-matched control rats and rats fed a high fat diet and treated with or without Ilepatril. Diabetic and diet induced obese rats have characteristics of insulin resistance, slowing of nerve conduction velocity, thermal hypoalgesia, reduction in intraepidermal nerve fiber density in the hindpaw and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles of the sciatic nerve. Treatment with Ilepatril was efficacious in improving all of these endpoints although improvement of insulin resistance in diabetic rats was minimal. These studies suggest that dual inhibition of angiotensin converting enzyme and neutral endopeptidase activity of type 2 diabetic rats is an effective approach for treatment of diabetic neural and vascular complications.

Diabetic neuropathy

Diabetes

Neutral endopeptidase

Vasopeptidase inhibitor

Angiotensin converting enzyme

Vascular relaxation

Details

Title: Subtitle: Effect of treatment of high fat fed/low dose streptozotocin-diabetic rats with Ilepatril on vascular and neural complications
Creators: Eric P Davidson - Department of Internal Medicine, University of Iowa, Iowa City, IA 52246, USA
Lawrence J Coppey - Department of Internal Medicine, University of Iowa, Iowa City, IA 52246, USA
Amey Holmes - Department of Veterans Affairs Iowa City Health Care System, University of Iowa, Iowa City, IA 52246, USA
Brian Dake - Department of Internal Medicine, University of Iowa, Iowa City, IA 52246, USA
Mark A Yorek - Department of Veterans Affairs Iowa City Health Care System, University of Iowa, Iowa City, IA 52246, USA
Resource Type: Journal article
Publication Details: European journal of pharmacology, Vol.668(3), pp.497-506
DOI: 10.1016/j.ejphar.2011.07.016
PMID: 21816138
PMCID: PMC3185159
NLM abbreviation: Eur J Pharmacol
ISSN: 0014-2999
eISSN: 1879-0712
Publisher: Elsevier B.V
Language: English
Date published: 2011
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094765802771

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