| 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. | |
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MedLine Citation:
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PMID: 22198047 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Eric P Davidson; Lawrence J Coppey; Amey Holmes; Mark A Yorek |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-14 |
Journal Detail:
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Title: European journal of pharmacology Volume: - ISSN: 1879-0712 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-26 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier B.V. |
Affiliation:
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Department of Internal Medicine, University of Iowa, Iowa City, IA, 52246, United States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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