Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase

<!DOCTYPE html> <html lang="en" > <head itemscope itemtype="http://schema.org/WebPage" prefix="og: http://ogp.me/ns#" > <meta charset="UTF-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge">  <meta name="HandheldFriendly" content="True"> <meta name="MobileOptimized" content="320"> <meta name="viewport" content="width=device-width, initial-scale=1.0"> <link rel="preconnect" href="https://cdn.ncbi.nlm.nih.gov"> <link rel="preconnect" href="https://www.ncbi.nlm.nih.gov"> <link rel="preconnect" href="https://www.google-analytics.com"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/277eb475-38df-4990-a0ee-0080b04e86fc/CACHE/css/output.ba8099dd2df4.css" type="text/css"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/277eb475-38df-4990-a0ee-0080b04e86fc/CACHE/css/output.452c70ce66f7.css" type="text/css"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/277eb475-38df-4990-a0ee-0080b04e86fc/CACHE/css/output.7bf600913d6e.css" type="text/css"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/277eb475-38df-4990-a0ee-0080b04e86fc/CACHE/css/output.0bfa59184c7a.css" type="text/css"> <title>Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase - 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PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/12093770/"><meta property="og:description" content="These results indicate that hypoxia-induced decrease in eNOS expression is mediated by Rho-kinase and suggest that Rho-kinase inhibitors may have therapeutic benefits in patients with hypoxia-induced pulmonary hypertension."><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/12093770/"><meta name="twitter:description" content="These results indicate that hypoxia-induced decrease in eNOS expression is mediated by Rho-kinase and suggest that Rho-kinase inhibitors may have therapeutic benefits in patients with hypoxia-induced pulmonary hypertension."><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">  <link rel="search" type="application/opensearchdescription+xml" href="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/opensearch.xml" title="PubMed search">  <noscript> <link rel="stylesheet" type="text/css" href="https://cdn.ncbi.nlm.nih.gov/pubmed/277eb475-38df-4990-a0ee-0080b04e86fc/core/no-script.css"> </noscript> <meta name="citation_title" content="Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase"> <meta name="citation_authors" content="Takemoto M;Sun J;Hiroki J;Shimokawa H;Liao JK;"> <meta name="citation_date" content="07/02/2002"> <meta name="citation_publisher" content="Circulation"> <meta name="citation_journal_title" content="Circulation"> <meta name="citation_pmid" content="12093770"> <meta name="citation_abstract_html_url" content="https://pubmed.ncbi.nlm.nih.gov/12093770/"> <meta name="citation_volume" content="106"> <meta name="citation_issue" content="1"> <meta name="citation_doi" content="10.1161/01.cir.0000020682.73694.ab"> <meta name="citation_issn" content="1524-4539"> <link rel="canonical" href="https://pubmed.ncbi.nlm.nih.gov/12093770/" /> </head> <body > <noscript> <div class="no-script-banner" id="no-script-banner"> <div class="warning-message"> <div class="warning-message-text"> This site needs JavaScript to work properly. 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usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"> <label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br> <a href="#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to My Bibliography </h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"> <input type="hidden" name="csrfmiddlewaretoken" value="JOURfTMzPm44qePpz8JAFapHVwEQRuEdWzc9q7ElnBi26LZjueb6rsOmb7ggZ9Vt"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li> <input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/> <label for="my-bibliography">My Bibliography</label> </li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br> <a href="#">Please try again</a> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your saved search </h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"> <input type="hidden" name="csrfmiddlewaretoken" value="JOURfTMzPm44qePpz8JAFapHVwEQRuEdWzc9q7ElnBi26LZjueb6rsOmb7ggZ9Vt"> <div class="action-panel-control-wrap"> <label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="action-panel-control-wrap"> <label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"> <a href="#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"> <span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"> <legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li> <input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label> </li> <li> <input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label> </li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"> <label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"> <label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"> <label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div> <input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"> <label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Create a file for external citation management software </h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="JOURfTMzPm44qePpz8JAFapHVwEQRuEdWzc9q7ElnBi26LZjueb6rsOmb7ggZ9Vt"> <input name="results-format" type="hidden" value="pubmed"/> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your RSS Feed </h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""> <input type="hidden" name="csrfmiddlewaretoken" value="JOURfTMzPm44qePpz8JAFapHVwEQRuEdWzc9q7ElnBi26LZjueb6rsOmb7ggZ9Vt"> <div class="action-panel-control-wrap"> <label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value='' required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected="selected">15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> <button class="action-panel-cancel" aria-label="Close 'Your RSS' panel" ref="linksrc=close_rss_panel" aria-controls="rss-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> <div class="action-panel-control-wrap rss-link-copy-wrap"> <label for="rss-link" class="usa-sr-only">RSS Link</label> <input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link"> <button type="button" disabled class="rss-link-copy-button disabled" data-ga-category="save_share" data-ga-action="rss" data-ga-label="copy"> Copy </button> </div> </form> </div> </div> </div> </div> <div class="article-page" id="article-page" data-article-pmid="12093770"> <aside class="page-sidebar"> <div class="inner-wrap"> <div class="full-text-links"> <div class="full-view"> <h3 class="title"> Full text links </h3> <div class="full-text-links-list"> <a class="link-item dialog-focus" href="https://www.ahajournals.org/doi/10.1161/01.cir.0000020682.73694.ab?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub 0pubmed" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=4487&itool=Abstract-def&log$=linkouticon&uid=12093770&db=pubmed&nlmid=0147763" title="See full text options at Atypon" data-ga-category="full_text" data-ga-action="Atypon" data-ga-label="12093770" ><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ahajournals.org-pb-assets-pubmed-images-CSA-circ.gif" alt="Atypon full text link"><span class="text"> Atypon </span></a> </div> </div> <div class="short-view"> <a href="#" class="full-text-links-button full-text-links-dialog-trigger"> Full text links </a> </div> </div> <div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/12093770/citations/" data-citation-style="nlm" data-pubmed-format-link="/12093770/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="12093770" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger" aria-label="Save article in MyNCBI collections." data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_button" data-collections-open-dialog-enabled="false" data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F12093770%2F%23open-collections-dialog" data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog" class="dialog collections-dialog" aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form" class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-existing-collections-url="/list-existing-collections/" data-add-to-existing-collection-url="/add-to-existing-collection/" data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/" data-myncbi-max-collection-name-length="100" data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="JOURfTMzPm44qePpz8JAFapHVwEQRuEdWzc9q7ElnBi26LZjueb6rsOmb7ggZ9Vt"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio" id="collections-action-dialog-new" class="collections-new" name="collections" value="new" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio" id="collections-action-dialog-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label><input type="text" name="add-to-new-collection" id="collections-action-dialog-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="collections_button" data-ga-action="create_collection" data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label"> Choose a collection: </label><select id="collections-action-dialog-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="collections_button" data-ga-action="select_collection" data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="collections_button" data-ga-action="click" data-ga-label="add"> Add </button><button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="collections_button" data-ga-action="click" data-ga-label="cancel"> Cancel </button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" 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id="article-details">   <header class="heading" id="heading"> <div class="full-view" id="full-view-heading"> <div class="article-citation"> <div class="article-source"> <div class="journal-actions dropdown-block"><button id="full-view-journal-trigger" class="journal-actions-trigger trigger" ref="linksrc=journal_actions_btn" title="Circulation" tabindex="0" aria-controls="full-view-journal" aria-expanded="false" aria-label="Toggle dropdown menu for journal Circulation" data-pinger-ignore> Circulation </button><div id="full-view-journal" class="journal-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for journal Circulation"><div class="title">Actions</div><div class="content"><ul class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Circulation%22%5Bjour%5D&sort=date&sort_order=desc" data-href="/?term=%22Circulation%22%5Bjour%5D&sort=date&sort_order=desc" 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Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase </h1> <div class="inline-authors"> <div class="authors"> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Takemoto+M&cauthor_id=12093770" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Masao Takemoto">Masao Takemoto</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Vascular Medicine Research Unit, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Mass 02139, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Sun+J&cauthor_id=12093770" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Jianxin Sun">Jianxin Sun</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Hiroki+J&cauthor_id=12093770" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Junko Hiroki">Junko Hiroki</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Shimokawa+H&cauthor_id=12093770" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Hiroaki Shimokawa">Hiroaki Shimokawa</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Liao+JK&cauthor_id=12093770" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="James K Liao">James K Liao</a></span> </div> </div> </div> <div class="short-article-details"> Affiliations <button class="more-details" id="toggle-authors" data-alt-text="Collapse" aria-controls="expanded-authors" 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ref="linksrc=article_id_link&article_id=10.1161/01.cir.0000020682.73694.ab&id_type=DOI" href="https://doi.org/10.1161/01.cir.0000020682.73694.ab" data-ga-category="full_text" data-ga-action="DOI" > 10.1161/01.cir.0000020682.73694.ab </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> <div class="short-view" id="short-view-heading"> <h1 class="heading-title"> Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase </h1> <div class="short-citation"> <span class="authors-list"> <span class="authors-list-item "><span class="full-name">Masao Takemoto</span><span class="citation-separator"> et al.</span></span> </span> <span class="citation-journal"> Circulation<span class="citation-separator">.</span> </span> <span class="date"> <time class="citation-year" datetime="2002">2002</time><span class="citation-separator">.</span> </span> </div> <div class="more-article-details-section with-display-settings"> <button 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id="short-view-expanded-authors"> <div class="authors"> <h3 class="title"> Authors </h3> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Takemoto+M&cauthor_id=12093770" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Masao Takemoto">Masao Takemoto</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Vascular Medicine Research Unit, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Mass 02139, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Sun+J&cauthor_id=12093770" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Jianxin Sun">Jianxin Sun</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Hiroki+J&cauthor_id=12093770" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Junko Hiroki">Junko Hiroki</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Shimokawa+H&cauthor_id=12093770" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Hiroaki Shimokawa">Hiroaki Shimokawa</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Liao+JK&cauthor_id=12093770" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="James K Liao">James K Liao</a></span> </div> </div> <div class="affiliations"> <h3 class="title"> Affiliation </h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1" ><sup class="key">1</sup> Vascular Medicine Research Unit, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Mass 02139, USA.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">12093770</strong> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1161/01.cir.0000020682.73694.ab&id_type=DOI" href="https://doi.org/10.1161/01.cir.0000020682.73694.ab" data-ga-category="full_text" data-ga-action="DOI" > 10.1161/01.cir.0000020682.73694.ab </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> </div> </header> <div class="actions-buttons inline"><div class="inner-wrap"><button class="full-text-links-button full-text-links-dialog-trigger" title="Open dialog with full text links" ref="linksrc=full_text_links"> Full text links </button><button 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</span><select name="format" data-initial-value="abstract" aria-label="Display format" id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="abstract" id="abstract"> <h2 class="title"> Abstract </h2> <div class="abstract-content selected" id="eng-abstract"> <p> <strong class="sub-title"> Background: </strong> Hypoxia-induced pulmonary hypertension is a major cause of morbidity and mortality. Hypoxia induces pulmonary vasoconstriction, in part, by decreasing endothelial nitric oxide synthase (eNOS) expression. The mechanism by which hypoxia decreases eNOS expression is not known but may involve Rho-kinase-induced actin cytoskeletal changes in vascular endothelial cells. </p> <p> <strong class="sub-title"> Methods and results: </strong> To determine whether hypoxia regulates eNOS expression through Rho-kinase, we exposed human saphenous and pulmonary artery endothelial cells to hypoxia (3% O2) with and without a Rho-kinase inhibitor, hydroxyfasudil (0.1 to 100 micromol/L), for various durations (0 to 48 hours). Hypoxia increased Rho-kinase expression and activity by 50% and 74%, decreased eNOS mRNA and protein expression by 66+/-3% and 57+/-5%, and inhibited eNOS activity by 48+/-9%. All of these effects of hypoxia on eNOS were reversed by cotreatment with hydroxyfasudil. Furthermore, inhibition of Rho by Clostridium botulinum C3 transferase or Rho-kinase by overexpression of dominant-negative Rho-kinase reversed hypoxia-induced decrease in eNOS expression. Indeed, disruption of the actin cytoskeleton, the downstream target of Rho-kinase, by cytochalasin D also upregulated eNOS expression. Hypoxia reduced eNOS mRNA half-life from 22+/-2 to 13+/-2 hours, which was reversed by cotreatment with hydroxyfasudil. However, neither hypoxia nor hydroxyfasudil had any effects on eNOS gene transcription. </p> <p> <strong class="sub-title"> Conclusions: </strong> These results indicate that hypoxia-induced decrease in eNOS expression is mediated by Rho-kinase and suggest that Rho-kinase inhibitors may have therapeutic benefits in patients with hypoxia-induced pulmonary hypertension. </p> </div> </div> <p class="disclaimer" id="disclaimer"> <a href="/disclaimer/" target="_blank" data-ga-category="literature_resources" data-ga-action="disclaimer_link" data-ga-label="under_abstract">PubMed Disclaimer</a> </p> <div class="similar-articles" id="similar"> <h2 class="title"> Similar articles </h2> <ul class="articles-list" id="similar-articles-list"> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/16141422/" ref="article_id=16141422&linksrc=similar_articles_link&ordinalpos=1" data-ga-category="similar_article" data-ga-action="16141422" data-ga-label=""> Inhibition of Rho kinase (ROCK) leads to increased cerebral blood flow and stroke protection. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Rikitake Y, Kim HH, Huang Z, Seto M, Yano K, Asano T, Moskowitz MA, Liao JK.</span> <span class="docsum-authors short-authors">Rikitake Y, et al.</span> <span class="docsum-journal-citation full-journal-citation">Stroke. 2005 Oct;36(10):2251-7. doi: 10.1161/01.STR.0000181077.84981.11. 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Epub 2007 Sep 20.</span> <span class="docsum-journal-citation short-journal-citation">J Mol Cell Cardiol. 2008.</span> <span class="citation-part">PMID: <span class="docsum-pmid">17950310</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> <span class="publication-type spaced-citation-item citation-part">Review.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/18001621/" ref="article_id=18001621&linksrc=citedby_articles_link&ordinalpos=4" data-ga-category="cited_by" data-ga-action="18001621" data-ga-label=""> Does it matter whether or not a lipid-lowering agent inhibits Rho kinase? </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Liao JK.</span> <span class="docsum-authors short-authors">Liao JK.</span> <span class="docsum-journal-citation full-journal-citation">Curr Atheroscler Rep. 2007 Nov;9(5):384-8. doi: 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<span class="docsum-journal-citation full-journal-citation">Laryngoscope Investig Otolaryngol. 2022 Apr 25;7(3):885-893. doi: 10.1002/lio2.796. eCollection 2022 Jun.</span> <span class="docsum-journal-citation short-journal-citation">Laryngoscope Investig Otolaryngol. 2022.</span> <span class="citation-part">PMID: <span class="docsum-pmid">35734065</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> </div> </div> </li> </ul> <div class="actions-bar"> <a class="show-all-linked-articles" data-href="/?linkname=pubmed_pubmed_citedin&from_uid=12093770" data-ga-category="cited_by" data-ga-action="show_all" > See all "Cited by" articles </a> </div> </div> <div id="publication-types" class="publication-types keywords-section"> <h2 class="title"> Publication types </h2> <ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for 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Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase - PubMed