| Role of the effect of inhibition of neutral endopeptidase on vascular and neural complications in streptozotocin-induced diabetic rats. | |
| | |
MedLine Citation:
|
PMID: 21040718 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Christine L Oltman; Eric P Davidson; Lawrence J Coppey; Travis L Kleinschmidt; Brian Dake; Mark A Yorek |
Related Documents
:
|
18784848 - Renal and vascular mechanisms of thiazolidinedione-induced fluid retention. 10405788 - Hypertension and insulin resistance: role of peroxisome proliferator-activated receptor... 9676728 - Oral administration of the antioxidant, n-acetylcysteine, abrogates diabetes-induced en... 16601768 - Pharmacotherapeutical approaches to decreasing hematocrit and increasing claudication d... 7928188 - Decreased rhodopsin regeneration in diabetic mouse eyes. 17065678 - Design and validation of a population-based definition of the metabolic syndrome. |
Publication Detail:
|
Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-10-30 |
Journal Detail:
|
Title: European journal of pharmacology Volume: 650 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2011 Jan |
Date Detail:
|
Created Date: 2010-12-14 Completed Date: 2011-05-02 Revised Date: 2012-03-07 |
Medline Journal Info:
|
Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 556-62 Citation Subset: IM |
Copyright Information:
|
Published by Elsevier B.V. |
Affiliation:
|
Department of Veterans Affairs Iowa City Health Care System, University of Iowa, Iowa City, IA 52246, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Angiotensin-Converting Enzyme Inhibitors
/
pharmacology Animals Diabetes Mellitus, Experimental / complications, drug therapy*, physiopathology Diabetic Angiopathies / drug therapy, etiology, physiopathology Diabetic Neuropathies / drug therapy, etiology, physiopathology Enalapril / pharmacology*, therapeutic use Heterocyclic Compounds, 3-Ring / pharmacology*, therapeutic use Indans / pharmacology*, therapeutic use Male Neprilysin / antagonists & inhibitors* Neural Conduction / drug effects* Propionates / pharmacology*, therapeutic use Rats Rats, Sprague-Dawley Sciatic Nerve / drug effects, physiopathology Streptozocin |
| Grant Support | |
ID/Acronym/Agency:
|
DK073990/DK/NIDDK NIH HHS; R01 DK073990-03/DK/NIDDK NIH HHS; R01 DK073990-05/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/AVE 7688; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Heterocyclic Compounds, 3-Ring; 0/Indans; 0/Propionates; 118785-03-8/candoxatril; 18883-66-4/Streptozocin; 75847-73-3/Enalapril; EC 3.4.24.11/Neprilysin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Chronic infusion of angiotensin receptor antagonists in the hypothalamic paraventricular nucleus pre...
Next Document: Inhibitory effect of fenofibrate on neointima hyperplasia via G(0)/G(1) arrest of cell proliferation...