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Blunted flow-mediated responses and diminished nitric oxide synthase expression in lymphatic thoracic ducts of a rat model of metabolic syndrome

Identifieur interne : 001465 ( Pmc/Checkpoint ); précédent : 001464; suivant : 001466

Blunted flow-mediated responses and diminished nitric oxide synthase expression in lymphatic thoracic ducts of a rat model of metabolic syndrome

Auteurs : Scott D. Zawieja ; Olga Gasheva ; David C. Zawieja ; Mariappan Muthuchamy

Source :

RBID : PMC:4796620

Abstract

Flow-mediated inhibition of contraction frequency is blunted in metabolic syndrome (MetSyn) thoracic ducts (TDs) despite a comparable response to exogenous NO. While the NOS inhibitor l-NAME abolished this difference, the ROS scavenging molecule tempol did not restore flow responses in MetSyn TDs. A significant reduction in eNOS in Metsyn TDs is found.


Url:
DOI: 10.1152/ajpheart.00664.2015
PubMed: 26637560
PubMed Central: 4796620


Affiliations:


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PMC:4796620

Le document en format XML

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<title xml:lang="en">Blunted flow-mediated responses and diminished nitric oxide synthase expression in lymphatic thoracic ducts of a rat model of metabolic syndrome</title>
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<name sortKey="Zawieja, Scott D" sort="Zawieja, Scott D" uniqKey="Zawieja S" first="Scott D." last="Zawieja">Scott D. Zawieja</name>
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<name sortKey="Gasheva, Olga" sort="Gasheva, Olga" uniqKey="Gasheva O" first="Olga" last="Gasheva">Olga Gasheva</name>
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<name sortKey="Zawieja, David C" sort="Zawieja, David C" uniqKey="Zawieja D" first="David C." last="Zawieja">David C. Zawieja</name>
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<author>
<name sortKey="Muthuchamy, Mariappan" sort="Muthuchamy, Mariappan" uniqKey="Muthuchamy M" first="Mariappan" last="Muthuchamy">Mariappan Muthuchamy</name>
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<name sortKey="Muthuchamy, Mariappan" sort="Muthuchamy, Mariappan" uniqKey="Muthuchamy M" first="Mariappan" last="Muthuchamy">Mariappan Muthuchamy</name>
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<series>
<title level="j">American Journal of Physiology - Heart and Circulatory Physiology</title>
<idno type="ISSN">0363-6135</idno>
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<p>Flow-mediated inhibition of contraction frequency is blunted in metabolic syndrome (MetSyn) thoracic ducts (TDs) despite a comparable response to exogenous NO. While the NOS inhibitor
<sc>l</sc>
-NAME abolished this difference, the ROS scavenging molecule tempol did not restore flow responses in MetSyn TDs. A significant reduction in eNOS in Metsyn TDs is found.</p>
</div>
</front>
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<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Am J Physiol Heart Circ Physiol</journal-id>
<journal-id journal-id-type="iso-abbrev">Am. J. Physiol. Heart Circ. Physiol</journal-id>
<journal-id journal-id-type="hwp">ajpheart</journal-id>
<journal-id journal-id-type="pmc">ajpheart</journal-id>
<journal-id journal-id-type="publisher-id">AJPHEART</journal-id>
<journal-title-group>
<journal-title>American Journal of Physiology - Heart and Circulatory Physiology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0363-6135</issn>
<issn pub-type="epub">1522-1539</issn>
<publisher>
<publisher-name>American Physiological Society</publisher-name>
<publisher-loc>Bethesda, MD</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">26637560</article-id>
<article-id pub-id-type="pmc">4796620</article-id>
<article-id pub-id-type="publisher-id">H-00664-2015</article-id>
<article-id pub-id-type="doi">10.1152/ajpheart.00664.2015</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Vascular Biology and Microcirculation</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Blunted flow-mediated responses and diminished nitric oxide synthase expression in lymphatic thoracic ducts of a rat model of metabolic syndrome</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Zawieja</surname>
<given-names>Scott D.</given-names>
</name>
<xref ref-type="author-notes" rid="fn1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gasheva</surname>
<given-names>Olga</given-names>
</name>
<xref ref-type="author-notes" rid="fn1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zawieja</surname>
<given-names>David C.</given-names>
</name>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Muthuchamy</surname>
<given-names>Mariappan</given-names>
</name>
</contrib>
<aff>Department of Medical Physiology, College of Medicine, Cardiovascular Research Institute, Division of Lymphatic Biology, Texas A&M Health Science Center, Texas A&M University, Temple, Texas</aff>
</contrib-group>
<author-notes>
<fn id="fn1" fn-type="equal">
<label>*</label>
<p>S. D. Zawieja and O. Gasheva contributed equally to this work.</p>
</fn>
<corresp id="cor1">Address for reprint requests and other correspondence: M. Muthuchamy,
<addr-line>Dept. of Medical Physiology, College of Medicine, Cardiovascular Research Institute, Division of Lymphatic Biology, Texas A&M Health Science Center, Texas A&M Univ., 702 SW H. K. Dodgen Loop, Temple, TX 76504</addr-line>
(e-mail:
<email>marim@tamu.edu</email>
).</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>4</day>
<month>12</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="ppub">
<day>1</day>
<month>2</month>
<year>2016</year>
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<pub-date pub-type="pmc-release">
<day>1</day>
<month>2</month>
<year>2017</year>
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<pmc-comment> PMC Release delay is 12 months and 0 days and was based on the . </pmc-comment>
<volume>310</volume>
<issue>3</issue>
<fpage>H385</fpage>
<lpage>H393</lpage>
<history>
<date date-type="received">
<day>20</day>
<month>8</month>
<year>2015</year>
</date>
<date date-type="accepted">
<day>23</day>
<month>11</month>
<year>2015</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2016 the American Physiological Society</copyright-statement>
<copyright-year>2016</copyright-year>
<copyright-holder>American Physiological Society</copyright-holder>
</permissions>
<self-uri content-type="pdf" xlink:href="zh400316000385.pdf"></self-uri>
<abstract abstract-type="precis">
<p>Flow-mediated inhibition of contraction frequency is blunted in metabolic syndrome (MetSyn) thoracic ducts (TDs) despite a comparable response to exogenous NO. While the NOS inhibitor
<sc>l</sc>
-NAME abolished this difference, the ROS scavenging molecule tempol did not restore flow responses in MetSyn TDs. A significant reduction in eNOS in Metsyn TDs is found.</p>
</abstract>
<abstract>
<p>Shear-dependent inhibition of lymphatic thoracic duct (TD) contractility is principally mediated by nitric oxide (NO). Endothelial dysfunction and poor NO bioavailability are hallmarks of vasculature dysfunction in states of insulin resistance and metabolic syndrome (MetSyn). We tested the hypothesis that flow-dependent regulation of lymphatic contractility is impaired under conditions of MetSyn. We utilized a 7-wk high-fructose-fed male Sprague-Dawley rat model of MetSyn and determined the stretch- and flow-dependent contractile responses in an isobaric ex vivo TD preparation. TD diameters were tracked and contractile parameters were determined in response to different transmural pressures, imposed flow, exogenous NO stimulation by
<italic>S</italic>
-nitro-
<italic>N</italic>
-acetylpenicillamine (SNAP), and inhibition of NO synthase (NOS) by
<sc>l</sc>
-nitro-arginine methyl ester (
<sc>l</sc>
-NAME) and the reactive oxygen species (ROS) scavenging molecule 4-hydroxy-tempo (tempol). Expression of endothelial NO synthase (eNOS) in TD was determined using Western blot. Approximately 25% of the normal flow-mediated inhibition of contraction frequency was lost in TDs isolated from MetSyn rats despite a comparable SNAP response. Inhibition of NOS with
<sc>l</sc>
-NAME abolished the differences in the shear-dependent contraction frequency regulation between control and MetSyn TDs, whereas tempol did not restore the flow responses in MetSyn TDs. We found a significant reduction in eNOS expression in MetSyn TDs suggesting that diminished NO production is partially responsible for impaired flow response. Thus our data provide the first evidence that MetSyn conditions diminish eNOS expression in TD endothelium, thereby affecting the flow-mediated changes in TD lymphatic function.</p>
</abstract>
<kwd-group>
<kwd>metabolic syndrome</kwd>
<kwd>lymphatic vessel contraction</kwd>
<kwd>lymph flow</kwd>
<kwd>nitric oxide synthase</kwd>
<kwd>lymphatic endothelial cells</kwd>
</kwd-group>
<funding-group>
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<funding-source>
<named-content content-type="funder-id">100000062</named-content>
HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</funding-source>
<award-id>RO1 DK99221</award-id>
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<name sortKey="Gasheva, Olga" sort="Gasheva, Olga" uniqKey="Gasheva O" first="Olga" last="Gasheva">Olga Gasheva</name>
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<name sortKey="Zawieja, David C" sort="Zawieja, David C" uniqKey="Zawieja D" first="David C." last="Zawieja">David C. Zawieja</name>
<name sortKey="Zawieja, Scott D" sort="Zawieja, Scott D" uniqKey="Zawieja S" first="Scott D." last="Zawieja">Scott D. Zawieja</name>
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