Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556


The Potential Role of Angiotensin Converting Enzyme and Vasopeptidase Inhibitors in the Treatment of Diabetic Neuropathy

Author(s): Mark A. Yorek

Affiliation: Room 204, Building 40, Department of Veterans Affairs Iowa City Health Care System, Iowa City, IA 52246, USA.


Diabetic neuropathy is a debilitating disorder that occurs in more than 50 percent of patients with diabetes. Evidence suggests that there are at least five major pathways involved in the development of diabetic neuropathy: metabolic, vascular, immunologic, neurohormonal growth factor deficiency, and extracellular matrix remodeling. In light of the complicated etiologies, an effective treatment for diabetic neuropathy has not yet been identified. Hyperglycemia increases tissue angiotensin II, which induces oxidative stress, endothelial damage and other pathologies including vasoconstriction, thrombosis, inflammation and vascular remodeling. Angiotensin converting enzyme inhibition and/or blocking of the angiotensin II receptor are recognized as first line treatment for nephropathy and cardiovascular disease in diabetes patients. A new class of drug in late stages of development is vasopeptidase inhibitors. This drug inhibits both angiotensin converting enzyme activity and neutral endopeptidase. Neutral endopeptidase is a protease that degrades a number of biologically active peptides including vasoactive peptides. However, little information is available about the potential benefits of these drugs on diabetic neuropathy. Pre-clinical studies suggest that these drugs may be useful in treating diabetic complications involving vascular tissue. The purpose of this review is to evaluate the use of angiotensin converting enzyme and vasopeptidase inhibitors in the treatment of diabetic neuropathy.

Keywords: Diabetic neuropathy, vascular function, angiotensin converting enzyme inhibitor, vasopeptidase inhibitor, natriuretic peptide, neutral endopeptidase

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Article Details

Page: [77 - 84]
Pages: 8
DOI: 10.2174/138945008783431736