title: Oxidative Stress-Dependent Coronary Endothelial Dysfunction in Obese Mice.
abstract: Obesity is involved in several cardiovascular diseases including coronary artery disease and endothelial dysfunction. Endothelial Endothelium vasodilator and vasoconstrictor agonists play a key role in regulation of vascular tone. In this study, we evaluated coronary vascular response in an 8 weeks diet-induced obese C57BL/6 mice model. Coronary perfusion pressure in response to acetylcholine in isolated hearts from obese mice showed increased vasoconstriction and reduced vasodilation responses compared with control mice. Vascular nitric oxide assessed in situ with DAF-2 DA showed diminished levels in coronary arteries from obese mice in both basal and acetylcholine-stimulated conditions. Also, released prostacyclin was decreased in heart perfusates from obese mice, along with plasma tetrahydrobiopterin level and endothelium nitric oxide synthase dimer/monomer ratio. Obesity increased thromboxane A2 synthesis and oxidative stress evaluated by superoxide and peroxynitrite levels, compared with control mice. Obese mice treated with apocynin, a NADPH oxidase inhibitor, reversed all parameters to normal levels. These results suggest that after 8 weeks on a high-fat diet, the increase in oxidative stress lead to imbalance in vasoactive substances and consequently to endothelial dysfunction in coronary arteries.
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados (Cinvestav) del Instituto Politécnico Nacional, México, D.F. México.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Gamez-Mendez
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados (Cinvestav) del Instituto Politécnico Nacional, México, D.F. México.
authors.forename: Hilda
authors.initials: H
authors.lastname: Vargas-Robles
authors.affiliation: Cinvestav Monterrey, Apodaca, N.L. México.
authors.forename: Amelia
authors.initials: A
authors.lastname: Ríos
authors.affiliation: Cinvestav Monterrey, Apodaca, N.L. México.
authors.forename: Bruno
authors.initials: B
authors.lastname: Escalante
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D059305:Diet, High-Fat; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006321:Heart / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine