Dietary nitrate supplementation increases diaphragm peak power in old mice

Key points Respiratory 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 p...

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Veröffentlicht in:The Journal of physiology 2020-10, Vol.598 (19), p.4357-4369
Hauptverfasser: Kumar, Ravi A., Kelley, Rachel C., Hahn, Dongwoo, Ferreira, Leonardo F.
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Kelley, Rachel C.
Hahn, Dongwoo
Ferreira, Leonardo F.
description Key points Respiratory 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. Inspiratory 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 
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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. Inspiratory 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 &lt; 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. Key points Respiratory 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.</description><identifier>ISSN: 0022-3751</identifier><identifier>ISSN: 1469-7793</identifier><identifier>EISSN: 1469-7793</identifier><identifier>DOI: 10.1113/JP280027</identifier><identifier>PMID: 33460123</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Aging ; Animals ; contractile function ; Diaphragm ; Dietary Supplements ; Drinking water ; Mice ; Muscle Contraction ; muscle force ; myofibrillar ; Nitrate reduction ; Nitrates ; Nitric oxide ; Phosphorylation ; Proteins ; Quality of Life ; Respiration ; Sarcopenia</subject><ispartof>The Journal of physiology, 2020-10, Vol.598 (19), p.4357-4369</ispartof><rights>2020 The Authors. The Journal of Physiology © 2020 The Physiological Society</rights><rights>2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.</rights><rights>Journal compilation © 2020 The Physiological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4799-d3b7981bf538b012d248a21e3c3d97f3b9d3e16acc667c869789c6565ef9bd6d3</citedby><cites>FETCH-LOGICAL-c4799-d3b7981bf538b012d248a21e3c3d97f3b9d3e16acc667c869789c6565ef9bd6d3</cites><orcidid>0000-0001-6581-5882</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10195135/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10195135/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33460123$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kumar, Ravi A.</creatorcontrib><creatorcontrib>Kelley, Rachel C.</creatorcontrib><creatorcontrib>Hahn, Dongwoo</creatorcontrib><creatorcontrib>Ferreira, Leonardo F.</creatorcontrib><title>Dietary nitrate supplementation increases diaphragm peak power in old mice</title><title>The Journal of physiology</title><addtitle>J Physiol</addtitle><description>Key points Respiratory 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. Inspiratory 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 &lt; 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. Key points Respiratory 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.</description><subject>Aging</subject><subject>Animals</subject><subject>contractile function</subject><subject>Diaphragm</subject><subject>Dietary Supplements</subject><subject>Drinking water</subject><subject>Mice</subject><subject>Muscle Contraction</subject><subject>muscle force</subject><subject>myofibrillar</subject><subject>Nitrate reduction</subject><subject>Nitrates</subject><subject>Nitric oxide</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Quality of Life</subject><subject>Respiration</subject><subject>Sarcopenia</subject><issn>0022-3751</issn><issn>1469-7793</issn><issn>1469-7793</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctO3jAQRi1UBH8pUp-gitQNm1A7k_iyqhCXwi-ksoC15dgTME3i1E5AvD2uuLRFYjXSzNHRN_oI-czoPmMMvq0vKklpJTbIitVclUIo-EBWeVWVIBq2TT6mdEspA6rUFtkGqDllFazI-sjjbOJDMfo5mhmLtExTjwOOs5l9GAs_2ogmYSqcN9NNNNdDMaH5VUzhHmM-F6F3xeAtfiKbnekT7j7PHXJ1cnx5eFqe__xxdnhwXtpaKFU6aIWSrO0akG0O4apamoohWHBKdNAqB8i4sZZzYSVXQirLG95gp1rHHeyQ70_eaWkHdDZHjabXU_RDfkQH4_X_l9Hf6OtwpxllqmHQZMPesyGG3wumWQ8-Wex7M2JYkq5qIYUARWVGv75Bb8MSx_xfpmpRcyGB_xXaGFKK2L2mYVT_aUi_NJTRL_-mfwVfKsnA_hNw73t8eFekL9cXrK6kgkfBUplG</recordid><startdate>20201001</startdate><enddate>20201001</enddate><creator>Kumar, Ravi A.</creator><creator>Kelley, Rachel C.</creator><creator>Hahn, Dongwoo</creator><creator>Ferreira, Leonardo F.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TS</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6581-5882</orcidid></search><sort><creationdate>20201001</creationdate><title>Dietary nitrate supplementation increases diaphragm peak power in old mice</title><author>Kumar, Ravi A. ; Kelley, Rachel C. ; Hahn, Dongwoo ; Ferreira, Leonardo F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4799-d3b7981bf538b012d248a21e3c3d97f3b9d3e16acc667c869789c6565ef9bd6d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aging</topic><topic>Animals</topic><topic>contractile function</topic><topic>Diaphragm</topic><topic>Dietary Supplements</topic><topic>Drinking water</topic><topic>Mice</topic><topic>Muscle Contraction</topic><topic>muscle force</topic><topic>myofibrillar</topic><topic>Nitrate reduction</topic><topic>Nitrates</topic><topic>Nitric oxide</topic><topic>Phosphorylation</topic><topic>Proteins</topic><topic>Quality of Life</topic><topic>Respiration</topic><topic>Sarcopenia</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kumar, Ravi A.</creatorcontrib><creatorcontrib>Kelley, Rachel C.</creatorcontrib><creatorcontrib>Hahn, Dongwoo</creatorcontrib><creatorcontrib>Ferreira, Leonardo F.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kumar, Ravi A.</au><au>Kelley, Rachel C.</au><au>Hahn, Dongwoo</au><au>Ferreira, Leonardo F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dietary nitrate supplementation increases diaphragm peak power in old mice</atitle><jtitle>The Journal of physiology</jtitle><addtitle>J Physiol</addtitle><date>2020-10-01</date><risdate>2020</risdate><volume>598</volume><issue>19</issue><spage>4357</spage><epage>4369</epage><pages>4357-4369</pages><issn>0022-3751</issn><issn>1469-7793</issn><eissn>1469-7793</eissn><abstract>Key points Respiratory 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. Inspiratory 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 &lt; 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. Key points Respiratory 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.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33460123</pmid><doi>10.1113/JP280027</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-6581-5882</orcidid><oa>free_for_read</oa></addata></record>
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subjects Aging
Animals
contractile function
Diaphragm
Dietary Supplements
Drinking water
Mice
Muscle Contraction
muscle force
myofibrillar
Nitrate reduction
Nitrates
Nitric oxide
Phosphorylation
Proteins
Quality of Life
Respiration
Sarcopenia
title Dietary nitrate supplementation increases diaphragm peak power in old mice
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