Journal article
Diet-induced obesity impairs endothelium-derived hyperpolarization via altered potassium channel signaling mechanisms
PLoS One, Vol.6(1), e16423
2011
Abstract
Background: The vascular endothelium plays a critical role in the control of blood flow. Altered endothelium-mediated vasodilator and vasoconstrictor mechanisms underlie key aspects of cardiovascular disease, including those in obesity. Whilst the mechanism of nitric oxide (NO)-mediated vasodilation has been extensively studied in obesity, little is known about the impact of obesity on vasodilation to the endothelium-derived hyperpolarization (EDH) mechanism; which predominates in smaller resistance vessels and is characterized in this study. Methodology/Principal Findings: Membrane potential, vessel diameter and luminal pressure were recorded in 4th order mesenteric arteries with pressure-induced myogenic tone, in control and diet-induced obese rats. Obesity, reflecting that of human dietary etiology, was induced with a cafeteria-style diet (~30 kJ, fat) over 16-20 weeks. Age and sexed matched controls received standard chow (~12 kJ, fat). Channel protein distribution, expression and vessel morphology were determined using immunohistochemistry, Western blotting and ultrastructural techniques. In control and obese rat vessels, acetylcholine-mediated EDH was abolished by small and intermediate conductance calcium-activated potassium channel (SKCa/IKCa) inhibition; with such activity being impaired in obesity. SKCa-IKCa activation with cyclohexyl-[2-(3,5-dimethylpyrazol- 1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) and 1-ethyl-2-benzimidazolinone (1-EBIO), respectively, hyperpolarized and relaxed vessels from control and obese rats. IKCa-mediated EDH contribution was increased in obesity, and associated with altered IKCa distribution and elevated expression. In contrast, the SKCa-dependent-EDH component was reduced in obesity. Inward-rectifying potassium channel (Kir) and Na+/K+-ATPase inhibition by barium/ouabain, respectively, attenuated and abolished EDH in arteries from control and obese rats, respectively; reflecting differential Kir expression and distribution. Although changes in medial properties occurred, obesity had no effect on myoendothelial gap junction density. Conclusion/Significance: In obese rats, vasodilation to EDH is impaired due to changes in the underlying potassium channel signaling mechanisms. Whilst myoendothelial gap junction density is unchanged in arteries of obese compared to control, increased IKCa and Na+/K+-ATPase, and decreased Kir underlie changes in the EDH mechanism. © 2011 Haddock et al.
Details
- Title
- Diet-induced obesity impairs endothelium-derived hyperpolarization via altered potassium channel signaling mechanisms
- Authors
- R E Haddock (Author) - University of New South WalesT Hilton Grayson (Author) - University of New South WalesM J Morris (Author) - University of New South WalesL Howitt (Author) - University of New South WalesP S Chadha (Author) - University of New South WalesShaun L Sandow (Author) - University of New South Wales
- Publication details
- PLoS One, Vol.6(1), e16423; 13
- Publisher
- Public Library of Science
- Date published
- 2011
- DOI
- 10.1371/journal.pone.0016423
- ISSN
- 1932-6203
- Copyright note
- Copyright © 2011 Haddock et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Organisation Unit
- School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99447763202621
- Output Type
- Journal article
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