Effect of inhibition of angiotensin converting enzyme and/or neutral endopeptidase on vascular and neural complications in high fat fed/low dose streptozotocin-diabetic rats

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

doi:10.1016/j.ejphar.2011.12.003

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Effect of inhibition of angiotensin converting enzyme and/or neutral endopeptidase on vascular and neural complications in high fat fed/low dose streptozotocin-diabetic rats

Journal article

Peer reviewed

Effect of inhibition of angiotensin converting enzyme and/or neutral endopeptidase on vascular and neural complications in high fat fed/low dose streptozotocin-diabetic rats

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

European journal of pharmacology, Vol.677(1-3), pp.180-187

02/29/2012

DOI: 10.1016/j.ejphar.2011.12.003

PMCID: PMC3268870

PMID: 22198047

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https://www.ncbi.nlm.nih.gov/pmc/articles/3268870View

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Abstract

Treating high fat fed/low dose streptozotocin-diabetic rats; model of type 2 diabetes, with ilepatril (vasopeptidase inhibitor, blocks neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE)) improved vascular and neural functions. Next, studies were performed to determine the individual effect of inhibition of NEP and ACE on diabetes-induced vascular and neural dysfunctions. High fat fed rats (8weeks) were treated with 30mg/kg streptozotocin (i.p.) and after 4 additional weeks, were treated for 12weeks with ilepatril, enalapril (ACE inhibitor) or candoxatril (NEP inhibitor) followed by analysis of vascular and neural functions. Glucose clearance was impaired in diabetic rats and was not improved with treatment although treatment with ilepatril or candoxatril partially improved insulin stimulated glucose uptake by isolated soleus muscle. Diabetes caused slowing of motor and sensory nerve conduction, thermal hypoalgesia, reduction in intraepidermal nerve fiber (IENF) profiles and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide (CGRP) in epineurial arterioles of the sciatic nerve. Inhibition of NEP improved nerve conduction velocity and inhibition of NEP or ACE improved thermal sensitivity and protected IENF density. Ilepatril and candoxatril treatments of diabetic rats were efficacious in improving vascular responsiveness to acetylcholine in epineurial arterioles; whereas all three treatments improved vascular response to CGRP. These studies suggest that inhibition of NEP and ACE activity is an effective approach for treatment of type 2 diabetes neural and vascular complications.

Diabetic neuropathy

Diabetes

Neutral endopeptidase

Vasopeptidase inhibitor

Angiotensin converting enzyme

Vascular relaxation

Details

Title: Subtitle: Effect of inhibition of angiotensin converting enzyme and/or neutral endopeptidase on vascular and neural complications in high fat fed/low dose streptozotocin-diabetic rats
Creators: Eric P Davidson - Department of Internal Medicine, University of Iowa, Iowa City, IA, 52246, United States
Lawrence J Coppey - Department of Internal Medicine, University of Iowa, Iowa City, IA, 52246, United States
Amey Holmes - Department of Veterans Affairs Iowa City Health Care System, United States
Mark A Yorek - Department of Veterans Affairs Iowa City Health Care System, United States
Resource Type: Journal article
Publication Details: European journal of pharmacology, Vol.677(1-3), pp.180-187
DOI: 10.1016/j.ejphar.2011.12.003
PMID: 22198047
PMCID: PMC3268870
NLM abbreviation: Eur J Pharmacol
ISSN: 0014-2999
eISSN: 1879-0712
Publisher: Elsevier B.V
Language: English
Date published: 02/29/2012
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094671502771

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