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Dietary nitrate is a modifier of vascular gene expression in old male mice.

ABSTRACT: Aging leads to a number of disadvantageous changes in the cardiovascular system. Deterioration of vascular homoeostasis with increase in oxidative stress, chronic low-grade inflammation, and impaired nitric oxide bioavailability results in endothelial dysfunction, increased vascular stiffness, and compromised arterial-ventricular interactions. A chronic dietary supplementation with the micronutrient nitrate has been demonstrated to improve vascular function. Healthy dietary patterns may regulate gene expression profiles. However, the mechanisms are incompletely understood. The changes that occur at the gene expression level and transcriptional profile following a nutritional modification with nitrate have not been elucidated. To determine the changes of the vascular transcriptome, we conducted gene expression microarray experiments on aortas of old mice, which were treated with dietary nitrate. Our results highlight differentially expressed genes overrepresented in gene ontology categories. Molecular interaction and reaction pathways involved in the calcium-signaling pathway and the detoxification system were identified. Our results provide novel insight to an altered gene-expression profile in old mice following nitrate supplementation. This supports the general notion of nutritional approaches to modulate age-related changes of vascular functions and its detrimental consequences.

SUBMITTER: Rammos C

PROVIDER: S-EPMC4369962 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Dietary nitrate is a modifier of vascular gene expression in old male mice.

Rammos Christos C Totzeck Matthias M Deenen René R Köhrer Karl K Kelm Malte M Rassaf Tienush T Hendgen-Cotta Ulrike B UB

Oxidative medicine and cellular longevity 20150308

Aging leads to a number of disadvantageous changes in the cardiovascular system. Deterioration of vascular homoeostasis with increase in oxidative stress, chronic low-grade inflammation, and impaired nitric oxide bioavailability results in endothelial dysfunction, increased vascular stiffness, and compromised arterial-ventricular interactions. A chronic dietary supplementation with the micronutrient nitrate has been demonstrated to improve vascular function. Healthy dietary patterns may regulate ...[more]

PMID: 25838870

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Project description:Key pointsRespiratory muscle function declines with ageing, contributing to breathing complications in the elderly. Here we report greater in vitro respiratory muscle contractile function in old mice receiving supplemental NaNO3 for 14 days compared with age-matched controls. Myofibrillar protein phosphorylation, which enhances contractile function, did not change in our study - a finding inconsistent with the hypothesis that this post-translational modification is a mechanism for dietary nitrate to improve muscle contractile function. Nitrate supplementation did not change the abundance of calcium-handling proteins in the diaphragm of old mice, in contrast with findings from the limb muscles of young mice in previous studies. Our findings suggest that nitrate supplementation enhances myofibrillar protein function without affecting the phosphorylation status of key myofibrillar proteins.AbstractInspiratory muscle (diaphragm) function declines with age, contributing to ventilatory dysfunction, impaired airway clearance, and overall decreased quality of life. Diaphragm isotonic and isometric contractile properties are reduced with ageing, including maximal specific force, shortening velocity and peak power. Contractile properties of limb muscle in both humans and rodents can be improved by dietary nitrate supplementation, but effects on the diaphragm and mechanisms behind these improvements remain poorly understood. One potential explanation underlying the nitrate effects on contractile properties is increased phosphorylation of myofibrillar proteins, a downstream outcome of nitrate reduction to nitrite and nitric oxide. We hypothesized that dietary nitrate supplementation would improve diaphragm contractile properties in aged mice. To test our hypothesis, we measured the diaphragm function of old (24 months) mice allocated to 1 mm NaNO3 in drinking water for 14 days (n = 8) or untreated water (n = 6). The maximal rate of isometric force development (∼30%) and peak power (40%) increased with nitrate supplementation (P < 0.05). There were no differences in the phosphorylation status of key myofibrillar proteins and abundance of Ca2+-release proteins in nitrate vs. control animals. In general, our study demonstrates improved diaphragm contractile function with dietary nitrate supplementation and supports the use of this strategy to improve inspiratory function in ageing populations. Additionally, our findings suggest that dietary nitrate improves diaphragm contractile properties independent of changes in abundance of Ca2+-release proteins or phosphorylation of myofibrillar proteins.

Dataset Information

Dietary nitrate is a modifier of vascular gene expression in old male mice.

Publications

Dietary nitrate is a modifier of vascular gene expression in old male mice.

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