Role of the effect of inhibition of neutral endopeptidase on vascular and neural complications in streptozotocin-induced diabetic rats

Christine L Oltman; Eric P Davidson; Lawrence J Coppey; Travis L Kleinschmidt; Brian Dake; Mark A Yorek

doi:10.1016/j.ejphar.2010.10.047

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Role of the effect of inhibition of neutral endopeptidase on vascular and neural complications in streptozotocin-induced diabetic rats

Journal article

Peer reviewed

Role of the effect of inhibition of neutral endopeptidase on vascular and neural complications in streptozotocin-induced diabetic rats

Christine L Oltman, Eric P Davidson, Lawrence J Coppey, Travis L Kleinschmidt, Brian Dake and Mark A Yorek

European journal of pharmacology, Vol.650(2), pp.556-562

2011

DOI: 10.1016/j.ejphar.2010.10.047

PMCID: PMC3016620

PMID: 21040718

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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 function. In this study we sought to determine the individual effect of inhibition of neutral endopeptidase and ACE on diabetes-induced vascular and neural dysfunction. After 4 weeks of untreated diabetes, rats were treated for 12 weeks with Ilepatril, Enalapril (ACE inhibitor) or Candoxatril (neutral endopeptidase inhibitor) followed by analysis of neural and vascular function. Diabetes caused slowing of motor and sensory nerve conduction, thermal hypoalgesia, reduction in intraepidermal nerve fiber density in the hindpaw and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineural arterioles of the sciatic nerve and to atrial natriuretic peptide and calcitonin gene-related peptide in renal arteries. Inhibition of neutral endopeptidase or ACE improved neural function; however, dual inhibition of neutral endopeptidase and ACE with Ilepatril tended to have the greatest efficacy. Ilepatril and Candoxatril treatment of diabetic rats was more efficacious in improving vascular responsiveness in epineurial arterioles than treatment with Enalapril. Ilepatril, Enalapril or Candoxatril treatment of diabetic rats were all efficacious in renal arteries. These studies suggest that combination therapy may be the most effective approach for treatment of diabetic neural and vascular complications.

Vasopeptidase inhibitor

Angiotensin converting enzyme

Diabetic neuropathy

Diabetic nephropathy

Diabetes

Neutral endopeptidase

Vascular relaxation

Details

Title: Subtitle: Role of the effect of inhibition of neutral endopeptidase on vascular and neural complications in streptozotocin-induced diabetic rats
Creators: Christine L Oltman - Department of Veterans Affairs Iowa City Health Care System, University of Iowa, Iowa City, IA, 52246, United States
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
Travis L Kleinschmidt - Department of Veterans Affairs Iowa City Health Care System, University of Iowa, Iowa City, IA, 52246, United States
Brian Dake - Department of Internal Medicine, University of Iowa, Iowa City, IA, 52246, United States
Mark A Yorek - Department of Veterans Affairs Iowa City Health Care System, University of Iowa, Iowa City, IA, 52246, United States
Resource Type: Journal article
Publication Details: European journal of pharmacology, Vol.650(2), pp.556-562
DOI: 10.1016/j.ejphar.2010.10.047
PMID: 21040718
PMCID: PMC3016620
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: 9984094718502771

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