Journal article
Dietary obesity increases NO and inhibits BKCa-mediated, endothelium-dependent dilation in rat cremaster muscle artery: Association with caveolins and caveolae
American Journal of Physiology - Heart and Circulatory Physiology, Vol.302(12), pp.H2464-H2476
2012
Abstract
Obesity is a risk factor for hypertension and other vascular disease. The aim of this study was to examine the effect of diet-induced obesity on endothelium-dependent dilation of rat cremaster muscle arterioles. Male Sprague-Dawley rats (213±1 g) were fed a cafeteria-style high-fat or control diet for 16-20 wk. Control rats weighed 558±7 g compared with obese rats 762±12 g (n = 52-56; P < 0.05). Diet-induced obesity had no effect on acetylcholine (ACh)-induced dilation of isolated, pressurized (70 mmHg) arterioles, but sodium nitroprusside (SNP)-induced vasodilation was enhanced. ACh-induced dilation of arterioles from control rats was abolished by a combination of the KCa blockers apamin, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), and iberiotoxin (IBTX; all 0.1 μmol/l), with no apparent role for nitric oxide (NO). In arterioles from obese rats, however, IBTX had no effect on responses to ACh while the NO synthase (NOS)/guanylate cyclase inhibitors Nω-nitro-L-arginine methyl ester (l-NAME; 100 μmol/l)/1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μmol/l) partially inhibited ACh-induced dilation. Furthermore, NOS activity (but not endothelial NOS expression) was increased in arteries from obese rats. l-NAME/ODQ alone or removal of the endothelium constricted arterioles from obese but not control rats. Expression of caveolin-1 and -2 oligomers (but not monomers or caveolin-3) was increased in arterioles from obese rats. The number of caveolae was reduced in the endothelium of arteries, and caveolae density was increased at the ends of smooth muscle cells from obese rats. Diet-induced obesity abolished the contribution of large-conductance Ca2+-activated K+ channel to ACh-mediated endothelium-dependent dilation of rat cremaster muscle arterioles, while increasing NOS activity and inducing an NO-dependent component. © 2012 the American Physiological Society.
Details
- Title
- Dietary obesity increases NO and inhibits BKCa-mediated, endothelium-dependent dilation in rat cremaster muscle artery: Association with caveolins and caveolae
- Authors
- L Howitt (Author) - University of New South WalesT Hilton Grayson (Author) - University of New South WalesM J Morris (Author) - University of New South WalesShaun L Sandow (Author) - University of New South WalesT V Murphy (Author) - University of New South Wales
- Publication details
- American Journal of Physiology - Heart and Circulatory Physiology, Vol.302(12), pp.H2464-H2476
- Publisher
- American Physiological Society
- Date published
- 2012
- DOI
- 10.1152/ajpheart.00965.2011
- ISSN
- 0363-6135
- Copyright note
- Copyright © 2012 American Physiological Society. The author's accepted version is reproduced here in accordance with the publisher's copyright policy. The final definitive version is available at: http://dx.doi.org/10.1152/ajpheart.00965.2011
- 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
- 99448866502621
- Output Type
- Journal article
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- Web Of Science research areas
- Cardiac & Cardiovascular Systems
- Peripheral Vascular Disease
- Physiology
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Source: InCites