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Vasopeptidase Inhibitor Improves Coronary Dysfunction in Zucker Obese but not Zucker Diabetic Fatty (ZDF) Rats
Author(s) -
Oltman Christine L.,
Kleinschmidt Travis L.,
Coppey Lawrence J.,
Davidson Eric P.,
Yorek Mark A.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.990.23
Subject(s) - medicine , dilator , endocrinology , endothelial dysfunction , mesenteric arteries , insulin resistance , vasodilation , diabetes mellitus , artery
Previous studies have shown endothelial dysfunction in coronary and mesenteric near resistance arteries in Zucker obese and ZDF rats. Our hypothesis is that vascular dysfunction is due in part to upreglulation of neutral endopeptidase and treatment with a vasopeptidase inhibitor will improve vascular function. 20‐week‐old Zucker obese and 12‐week‐old ZDF rats were treated with the vasopeptidase inhibitor AVE7688 (500mg/kg) for 12 weeks. Afterwards, coronary and mesenteric function was evaluated using an isolated vessel preparation. Vessels (75 ‐ 175µm intraluminal diameter and ~1 mm in length) were studied under hydrostatic pressure (40mm Hg) and no flow, and internal diameter was measured. Dilator responses were evaluated for acetylcholine (Ach, 10 −10 ‐10 −4 M), and calcitonin gene‐related peptide (CGRP, 10 −11 ‐10 −9 M) after constriction with U46619. Results ACh (10μM) responses were attenuated in arteries from untreated rats compared to responses from lean rats (coronary: Zucker obese = 49.4%, ZDF = 50.7% decrease and mesenteric: Zucker obese = 27.4%, ZDF = 33.5% decrease). ACh response was augmented in coronary vessels from AVE7688 treated Zucker obese but not ZDF rats when compared to vessels from untreated rats. Our data suggest that coronary artery endothelial dysfunction is improved when Zucker obese but not ZDF rats were treated with AVE7688. Supported by VA Merits to Dr. Oltman and Dr. Yorek.