Increased caveolae density and caveolin-1 expression accompany impaired NO-mediated vasorelaxation in diet-induced obesity

T Hilton Grayson; P S Chadha; P P Bertrand; H Chen; M J Morris; S Senadheera; T V Murphy; Shaun L Sandow

doi:10.1007/s00418-012-1032-2

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Increased caveolae density and caveolin-1 expression accompany impaired NO-mediated vasorelaxation in diet-induced obesity

Journal article

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Increased caveolae density and caveolin-1 expression accompany impaired NO-mediated vasorelaxation in diet-induced obesity

T Hilton Grayson, P S Chadha, P P Bertrand, H Chen, M J Morris, S Senadheera, T V Murphy and Shaun L Sandow

Histochemistry and Cell Biology, Vol.139(2), pp.309-321

2013

DOI: https://doi.org/10.1007/s00418-012-1032-2

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Abstract

artery

caveolin

caveolae

dietary obesity

endothelial nitric oxide synthase

nitric oxide

vasorelaxation

Diet-induced obesity induces changes in mechanisms that are essential for the regulation of normal artery function, and in particular the function of the vascular endothelium. Using a rodent model that reflects the characteristics of human dietary obesity, in the rat saphenous artery we have previously demonstrated that endothelium-dependent vasodilation shifts from an entirely nitric oxide (NO)-mediated mechanism to one involving upregulation of myoendothelial gap junctions and intermediate conductance calcium-activated potassium channel activity and expression. This study investigates the changes in NO-mediated mechanisms that accompany this shift. In saphenous arteries from controls fed a normal chow diet, acetylcholine-mediated endothelium-dependent vasodilation was blocked by NO synthase and soluble guanylyl cyclase inhibitors, but in equivalent arteries from obese animals sensitivity to these agents was reduced. The expression of endothelial NO synthase (eNOS) and caveolin-3 in rat saphenous arteries was unaffected by obesity, whilst that of caveolin-1 monomer and large oligomeric complexes of caveolins-1 and -2 were increased in membrane-enriched samples. The density of caveolae was increased at the membrane and cytoplasm of endothelial and smooth muscle cells of saphenous arteries from obese rats. Dissociation of eNOS from caveolin-1, as a prerequisite for activation of the enzyme, may be compromised and thereby impair NO-mediated vasodilation in the saphenous artery from diet-induced obese rats. Such altered signaling mechanisms in obesity-related vascular disease represent significant potential targets for therapeutic intervention. © 2012 Springer-Verlag.

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Title: Increased caveolae density and caveolin-1 expression accompany impaired NO-mediated vasorelaxation in diet-induced obesity
Authors: T Hilton Grayson (Author) - University of New South Wales
P S Chadha (Author) - University of New South Wales
P P Bertrand (Author) - University of New South Wales
H Chen (Author) - University of Technology Sydney
M J Morris (Author) - University of New South Wales
S Senadheera (Author) - University of New South Wales
T V Murphy (Author) - University of New South Wales
Shaun L Sandow (Author) - University of New South Wales
Publication details: Histochemistry and Cell Biology, Vol.139(2), pp.309-321
Publisher: Springer
Date published: 2013
DOI: 10.1007/s00418-012-1032-2
ISSN: 0948-6143
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: 99448883302621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Cell Biology; Microscopy

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