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Increasing muscle mass improves vascular function in obese (db/db) mice.
- Source :
-
Journal of the American Heart Association [J Am Heart Assoc] 2014 Jun 25; Vol. 3 (3), pp. e000854. Date of Electronic Publication: 2014 Jun 25. - Publication Year :
- 2014
-
Abstract
- Background: A sedentary lifestyle is an independent risk factor for cardiovascular disease and exercise has been shown to ameliorate this risk. Inactivity is associated with a loss of muscle mass, which is also reversed with isometric exercise training. The relationship between muscle mass and vascular function is poorly defined. The aims of the current study were to determine whether increasing muscle mass by genetic deletion of myostatin, a negative regulator of muscle growth, can influence vascular function in mesenteric arteries from obese db/db mice.<br />Methods and Results: Myostatin expression was elevated in skeletal muscle of obese mice and associated with reduced muscle mass (30% to 50%). Myostatin deletion increased muscle mass in lean (40% to 60%) and obese (80% to 115%) mice through increased muscle fiber size (P<0.05). Myostatin deletion decreased adipose tissue in lean mice, but not obese mice. Markers of insulin resistance and glucose tolerance were improved in obese myostatin knockout mice. Obese mice demonstrated an impaired endothelial vasodilation, compared to lean mice. This impairment was improved by superoxide dismutase mimic Tempol. Deletion of myostatin improved endothelial vasodilation in mesenteric arteries in obese, but not in lean, mice. This improvement was blunted by nitric oxide (NO) synthase inhibitor l-NG-nitroarginine methyl ester (l-NAME). Prostacyclin (PGI2)- and endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilation were preserved in obese mice and unaffected by myostatin deletion. Reactive oxygen species) was elevated in the mesenteric endothelium of obese mice and down-regulated by deletion of myostatin in obese mice. Impaired vasodilation in obese mice was improved by NADPH oxidase inhibitor (GKT136901). Treatment with sepiapterin, which increases levels of tetrahydrobiopterin, improved vasodilation in obese mice, an improvement blocked by l-NAME.<br />Conclusions: Increasing muscle mass by genetic deletion of myostatin improves NO-, but not PGI2- or EDHF-mediated vasodilation in obese mice; this vasodilation improvement is mediated by down-regulation of superoxide.<br /> (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)
- Subjects :
- Amino Acids
Animals
Chromium
Cyclic N-Oxides pharmacology
Insulin Resistance physiology
Male
Mice, Knockout
Muscle Strength drug effects
Muscle Strength physiology
Muscle, Skeletal
Myostatin genetics
Myostatin physiology
NADPH Oxidases antagonists & inhibitors
NG-Nitroarginine Methyl Ester pharmacology
Nicotinic Acids
Nitric Oxide Synthase antagonists & inhibitors
Pterins pharmacology
Pyrazoles pharmacology
Pyridones pharmacology
Reactive Oxygen Species analysis
Real-Time Polymerase Chain Reaction
Spin Labels
Vasodilation drug effects
Vasodilation physiology
Blood Vessels physiology
Mice, Obese physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2047-9980
- Volume :
- 3
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of the American Heart Association
- Publication Type :
- Academic Journal
- Accession number :
- 24965025
- Full Text :
- https://doi.org/10.1161/JAHA.114.000854