title: Effect of treatment of high fat fed/low dose streptozotocin-diabetic rats with Ilepatril on vascular and neural complications.
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 functions. In this study we sought to determine the effect of Ilepatril treatment of high fat fed/low dose streptozotocin-diabetic rats, a model for type 2 diabetes, on vascular and neural complications. Following 8 weeks on a high fat diet rats were treated with 30 mg/kg streptozotocin (i.p.) and after 4 additional weeks a group of these rats was treated for 12 weeks with Ilepatril followed by analysis of neural and vascular functions. Included in these studies were age-matched control rats and rats fed a high fat diet and treated with or without Ilepatril. Diabetic and diet induced obese rats have characteristics of insulin resistance, slowing of nerve conduction velocity, thermal hypoalgesia, reduction in intraepidermal nerve fiber density in the hindpaw and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles of the sciatic nerve. Treatment with Ilepatril was efficacious in improving all of these endpoints although improvement of insulin resistance in diabetic rats was minimal. These studies suggest that dual inhibition of angiotensin converting enzyme and neutral endopeptidase activity of type 2 diabetic rats is an effective approach for treatment of diabetic neural and vascular complications.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA 52246, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Davidson
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Coppey
authors.forename: Amey
authors.initials: A
authors.lastname: Holmes
authors.forename: Brian
authors.initials: B
authors.lastname: Dake
authors.forename: Mark A
authors.initials: MA
authors.lastname: Yorek
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001835:Body Weight / Q000187:drug effects; D050260:Carbohydrate Metabolism / Q000187:drug effects; D048909:Diabetes Complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005951:Glucose Tolerance Test; D005978:Glutathione / Q000378:metabolism; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009420:Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D059225:Nociception / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism; D013858:Thiobarbiturates / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: C479877:AVE 7688; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D007328:Insulin; D020738:Leptin; D013858:Thiobarbiturates; D013481:Superoxides; C002744:3-nitrotyrosine; D014443:Tyrosine; D005978:Glutathione; C029684:thiobarbituric acid