pubmed.ncbi.nlm.nih.gov
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Submitted URL: https://r20.rs6.net/tn.jsp?f=001vRSj4sAlO7OPhsSmlZ9b5Dy0Xs3kNLSLSxeXyrtvnQNLmyrQ5YcMTekB9RovG3zBzrCIDBGobUMZytijeGqG...
Effective URL: https://pubmed.ncbi.nlm.nih.gov/35498050/
Submission: On May 05 via api from US — Scanned from DE
Effective URL: https://pubmed.ncbi.nlm.nih.gov/35498050/
Submission: On May 05 via api from US — Scanned from DE
Form analysis
9 forms found in the DOMGET /
<form action="/" method="get" autocomplete="off" class="usa-search usa-search-big search-form content-page-layout" id="search-form" role="search">
<div class="inner-wrap">
<a class="pubmed-logo" aria-label="Pubmed Logo" href="/" data-ga-category="featured_link" data-ga-action="pubmed_logo">
<img src="https://cdn.ncbi.nlm.nih.gov/pubmed/ca993e9d-6117-4cbd-8ec4-f6eb2385bc9f/core/images/pubmed-logo-blue.svg" alt="pubmed logo">
</a>
<a href="#" class="search-input-trigger" data-alt-title="Hide search bar" title="Show search bar" aria-label="Show search bar" aria-hidden="true" tabindex="-1">
</a>
<div role="search" class="search-input">
<div class="form-field ">
<label class="usa-sr-only" for="id_term"> Search: </label>
<span class="twitter-typeahead ncbi-autocomplete"><input type="search" name="term" data-skip-ie-scroll-to-top="" data-replace-term-with-exact="" data-exact-query="" placeholder="" class="term-input tt-input" required="required" id="id_term"
spellcheck="false" dir="auto" style="position: relative; vertical-align: top;" aria-owns="id_term_listbox" role="combobox" aria-autocomplete="list" aria-expanded="false"><span role="status" aria-live="polite"
style="position: absolute; padding: 0px; border: 0px; height: 1px; width: 1px; margin-bottom: -1px; margin-right: -1px; overflow: hidden; clip: rect(0px, 0px, 0px, 0px); white-space: nowrap;"></span>
<pre aria-hidden="true"
style="position: absolute; visibility: hidden; white-space: pre; font-family: BlinkMacSystemFont, -apple-system, "Segoe UI", Roboto, Oxygen, Ubuntu, Cantarell, "Fira Sans", "Droid Sans", "Helvetica Neue", sans-serif; font-size: 16px; font-style: normal; font-variant: normal; font-weight: 400; word-spacing: 0px; letter-spacing: 0px; text-indent: 0px; text-rendering: auto; text-transform: none;"></pre>
<div role="listbox" class="tt-menu" id="id_term_listbox" style="position: absolute; top: 100%; left: 0px; z-index: 100; display: none;">
<div role="presentation" class="tt-dataset tt-dataset-0"></div>
</div>
</span><a href="#" class="clear-btn" title="Clear search input" role="button" data-pinger-ignore=""></a><button type="submit" class="search-btn" aria-label="Search" data-pinger-ignore=""><span
class="usa-search-submit-text">Search</span></button>
</div>
</div>
<!-- Create alert and Create RSS are buttons that look like links -->
<!-- Better for them to look like buttons but no space -->
<div class="search-links-wrapper content-page-layout">
<div class="search-links">
<a href="/advanced/" class="search-input-link adv-search-link" data-ga-category="featured_link" data-ga-action="adv_search">Advanced</a>
<a href="/clipboard/" class="search-input-link clipboard-link hidden" data-ga-category="featured_link" data-ga-action="clipboard">
Clipboard <span class="amount-in-clipboard"></span>
</a>
</div>
<span class="search-input-link user-guide-link" role="navigation" aria-label="User guide">
<a href="/help/" data-ga-category="featured_link" data-ga-action="user_guide">
User Guide
</a>
</span>
</div>
</div>
</form>
POST /results-export-ids/
<form id="save-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="6eiRsXBcHc3hpQlkavw9XDaqtzxBszrWebp7JjsEe8c3HT6UGhVsKLsHHmw0y7h1">
<div class="action-panel-control-wrap">
<label for="save-action-format" class="action-panel-label"> Format: </label>
<select id="save-action-format" name="results-format" class="action-panel-selector">
<option value="summary-text">Summary (text)</option>
<option value="pubmed-text">PubMed</option>
<option value="pmid">PMID</option>
<option value="abstract">Abstract (text)</option>
<option value="csv">CSV</option>
</select>
</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="save" data-ga-label="save"> Create file </button>
<button class="action-panel-cancel" aria-label="Close 'Save citations to file' panel" ref="linksrc=close_save_panel" aria-controls="save-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="save"
data-ga-label="cancel"> Cancel </button>
</div>
</form>
POST /send-email/
<form id="email-action-panel-form" class="action-panel-content action-form" action="/send-email/" data-by-search-action="/results-export-email-by-search-data/" data-by-ids-action="/send-email/" data-by-search-method="post" data-by-ids-method="post"
method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="6eiRsXBcHc3hpQlkavw9XDaqtzxBszrWebp7JjsEe8c3HT6UGhVsKLsHHmw0y7h1">
<div class="action-panel-control-wrap">
<span class="action-panel-label"> Subject: </span>
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 35498050 - PubMed</span>
<input type="hidden" name="email-subject" value="1 selected item: 35498050">
<input type="hidden" name="email-subject-hash" value="f893105225b488fadf83b7b38e966e2155d75432692dea2762156a10f04f53fc">
</div>
<div class="action-panel-control-wrap">
<label for="email-to" class="action-panel-label required-field-asterisk"> To: </label>
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required="">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label"> Format: </label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container" style="display: none;">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="email" data-ga-label="send"> Send email </button>
<button class="action-panel-cancel" aria-label="Close 'Email citations' panel" ref="linksrc=close_email_panel" aria-controls="email-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="email" data-ga-label="cancel">
Cancel </button>
</div>
<input type="hidden" name="email-search-details" value="">
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524">
</form>
<form id="collections-action-panel-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-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100" data-add-to-collection-max-amount="1000" data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="6eiRsXBcHc3hpQlkavw9XDaqtzxBszrWebp7JjsEe8c3HT6UGhVsKLsHHmw0y7h1">
<div class="choice-group">
<ul class="radio-group-items">
<li>
<input type="radio" id="collections-new" class="collections-new" name="collections" value="new">
<label for="collections-new">Create a new collection</label>
</li>
<li>
<input type="radio" id="collections-existing" class="collections-existing" name="collections" value="existing" checked="">
<label for="collections-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-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-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>/]*" title="The following characters are not allowed in the Name field: "&=<>/"
maxlength="100">
<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-add-to-existing" class="action-panel-label"> Choose a collection: </label>
<select id="collections-action-add-to-existing" class="action-panel-selector collections-action-add-to-existing"></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="" disabled=""> 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="collection"
data-ga-label="cancel"> Cancel </button>
</div>
</form>
<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="6eiRsXBcHc3hpQlkavw9XDaqtzxBszrWebp7JjsEe8c3HT6UGhVsKLsHHmw0y7h1">
<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>
<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="6eiRsXBcHc3hpQlkavw9XDaqtzxBszrWebp7JjsEe8c3HT6UGhVsKLsHHmw0y7h1">
<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" style="display: none;">
<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>
POST /results-export-ids/
<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="6eiRsXBcHc3hpQlkavw9XDaqtzxBszrWebp7JjsEe8c3HT6UGhVsKLsHHmw0y7h1">
<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>
<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="6eiRsXBcHc3hpQlkavw9XDaqtzxBszrWebp7JjsEe8c3HT6UGhVsKLsHHmw0y7h1">
<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>
POST
<form method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="6eiRsXBcHc3hpQlkavw9XDaqtzxBszrWebp7JjsEe8c3HT6UGhVsKLsHHmw0y7h1">
<button type="submit" class="export-button" data-ga-category="save_share" data-ga-action="cite" data-ga-label="download" title="Download a file for external citation management software" tabindex="3"> Download .nbib </button>
</form>
Text Content
This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features! Clipboard, Search History, and several other advanced features are temporarily unavailable. Skip to main page content An official website of the United States government Here's how you know The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site. The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. Log in Show account info Close ACCOUNT Logged in as: username * Dashboard * Publications * Account settings * Log out Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Search: Search Advanced Clipboard User Guide Save Email Send to * Clipboard * My Bibliography * Collections * Citation manager Display options Display options Format Abstract PubMed PMID SAVE CITATION TO FILE Format: Summary (text) PubMed PMID Abstract (text) CSV Create file Cancel EMAIL CITATION Subject: 1 selected item: 35498050 - PubMed To: Format: Summary Summary (text) Abstract Abstract (text) MeSH and other data Send email Cancel ADD TO COLLECTIONS * Create a new collection * Add to an existing collection Name your collection: Name must be less than 100 characters Choose a collection: Unable to load your collection due to an error Please try again Add Cancel ADD TO MY BIBLIOGRAPHY * My Bibliography Unable to load your delegates due to an error Please try again Add Cancel YOUR SAVED SEARCH Name of saved search: Search terms: Test search terms Would you like email updates of new search results? Saved Search Alert Radio Buttons * Yes * No Email: (change) Frequency: Monthly Weekly Daily Which day? The first Sunday The first Monday The first Tuesday The first Wednesday The first Thursday The first Friday The first Saturday The first day The first weekday Which day? Sunday Monday Tuesday Wednesday Thursday Friday Saturday Report format: Summary Summary (text) Abstract Abstract (text) PubMed Send at most: 1 item 5 items 10 items 20 items 50 items 100 items 200 items Send even when there aren't any new results Optional text in email: Save Cancel CREATE A FILE FOR EXTERNAL CITATION MANAGEMENT SOFTWARE Create file Cancel YOUR RSS FEED Name of RSS Feed: Number of items displayed: 5 10 15 20 50 100 Create RSS Cancel RSS Link Copy FULL TEXT LINKS Frontiers Media SA Free PMC article Full text links ACTIONS Cite Favorites Display options Display options Format AbstractPubMedPMID SHARE * * * Permalink Copy PAGE NAVIGATION * Title & authors * Abstract * Conflict of interest statement * Figures * References * Publication types * Associated data * LinkOut - more resources Title & authors Abstract Conflict of interest statement Figures References Publication types Associated data LinkOut - more resources Case Reports Front Cardiovasc Med Actions * Search in PubMed * Search in NLM Catalog * Add to Search . 2022 Apr 12;9:868521. doi: 10.3389/fcvm.2022.868521. eCollection 2022. L-ARGININE IMPROVES COGNITIVE IMPAIRMENT IN HYPERTENSIVE FRAIL OLDER ADULTS Pasquale Mone 1 2 3 , Antonella Pansini 2 , Stanislovas S Jankauskas 1 , Fahimeh Varzideh 1 , Urna Kansakar 1 , Angela Lombardi 1 , Valentina Trimarco 4 , Salvatore Frullone 2 , Gaetano Santulli 1 4 Affiliations Collapse AFFILIATIONS * 1 Department of Medicine, Albert Einstein College of Medicine, New York, NY, United States. * 2 Azienda Sanitaria Locale (ASL) Avellino, Avellino, Italy. * 3 Campania University, Naples, Italy. * 4 University of Naples "Federico II", Naples, Italy. * PMID: 35498050 * PMCID: PMC9039514 * DOI: 10.3389/fcvm.2022.868521 Free PMC article Item in Clipboard Case Reports L-ARGININE IMPROVES COGNITIVE IMPAIRMENT IN HYPERTENSIVE FRAIL OLDER ADULTS Pasquale Mone et al. Front Cardiovasc Med. 2022. Free PMC article Show details Display options Display options Format Abstract PubMed PMID Front Cardiovasc Med Actions * Search in PubMed * Search in NLM Catalog * Add to Search . 2022 Apr 12;9:868521. doi: 10.3389/fcvm.2022.868521. eCollection 2022. AUTHORS Pasquale Mone 1 2 3 , Antonella Pansini 2 , Stanislovas S Jankauskas 1 , Fahimeh Varzideh 1 , Urna Kansakar 1 , Angela Lombardi 1 , Valentina Trimarco 4 , Salvatore Frullone 2 , Gaetano Santulli 1 4 AFFILIATIONS * 1 Department of Medicine, Albert Einstein College of Medicine, New York, NY, United States. * 2 Azienda Sanitaria Locale (ASL) Avellino, Avellino, Italy. * 3 Campania University, Naples, Italy. * 4 University of Naples "Federico II", Naples, Italy. * PMID: 35498050 * PMCID: PMC9039514 * DOI: 10.3389/fcvm.2022.868521 Item in Clipboard Full text links Cite Display options Display options Format AbstractPubMedPMID ABSTRACT Cognitive impairment is a prevailing event in hypertensive patients and in frail older adults. Endothelial dysfunction has been shown to underlie both hypertension and cognitive dysfunction. Our hypothesis is that L-Arginine, which is known to ameliorate endothelial dysfunction, could counteract cognitive impairment in a high-risk population of hypertensive frail older adults. We designed a clinical trial to verify the effects of 4-weeks oral supplementation of L-Arginine on global cognitive function of hypertensive frail older patients. The study was successfully completed by 35 frail hypertensive elderly patients assigned to L-Arginine and 37 assigned to placebo. At follow-up, we found a significant difference in the Montreal Cognitive Assessment (MoCA) test score between the L-Arginine treated group and placebo (p: 0.0178). Moreover, we demonstrated that L-Arginine significantly attenuates Angiotensin II-induced mitochondrial oxidative stress in human endothelial cells. In conclusion, our findings indicate for the first time that oral L-Arginine supplementation significantly improves cognitive impairment in frail hypertensive older adults. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT04962841. Keywords: L-Arg; L-Arginine; cardiac rehabilitation; cognitive impairment; endothelial (dys)function; frail adults; frailty. Copyright © 2022 Mone, Pansini, Jankauskas, Varzideh, Kansakar, Lombardi, Trimarco, Frullone and Santulli. CONFLICT OF INTEREST STATEMENT The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. FIGURES Figure 1 Flow chart of the study. Figure 1 Flow chart of the study. Figure 1 Flow chart of the study. Figure 2 MoCA (Montreal Cognitive Assessment) score… Figure 2 MoCA (Montreal Cognitive Assessment) score evaluated at baseline and at follow-up in the… Figure 2 MoCA (Montreal Cognitive Assessment) score evaluated at baseline and at follow-up in the placebo and in the L-Arginine arms. Data are means ± SE; *: p < 0.05. Figure 3 Mitochondrial production of reactive oxygen… Figure 3 Mitochondrial production of reactive oxygen species (ROS) evaluated in human endothelial cells treated… Figure 3 Mitochondrial production of reactive oxygen species (ROS) evaluated in human endothelial cells treated with Angiotensin II (Ang II) (1 μM) + vehicle or Ang II + L-Arginine (500 μM) for 24 hours; A.U., arbitrary units. Data are means ± SE; *: p < 0.01. See this image and copyright information in PMC REFERENCES 1. 1. Iaccarino G, Ciccarelli M, Sorriento D, Cipolletta E, Cerullo V, Iovino GL, et al. . AKT participates in endothelial dysfunction in hypertension. Circulation. (2004) 109:2587–93. 10.1161/01.CIR.0000129768.35536.FA - DOI - PubMed 2. 1. Santisteban MM, Ahn SJ, Lane D, Faraco G, Garcia-Bonilla L, Racchumi G, et al. . Endothelium-macrophage crosstalk mediates blood-brain barrier dysfunction in hypertension. Hypertension. (2020) 76:795–807. 10.1161/HYPERTENSIONAHA.120.15581 - DOI - PMC - PubMed 3. 1. de Montgolfier O, Pincon A, Pouliot P, Gillis MA, Bishop J, Sled JG, et al. . High systolic blood pressure induces cerebral microvascular endothelial dysfunction, neurovascular unit damage, and cognitive decline in mice. Hypertension. (2019) 73:217–28. 10.1161/HYPERTENSIONAHA.118.12048 - DOI - PubMed 4. 1. Shimbo D, Muntner P, Mann D, Viera AJ, Homma S, Polak JF, et al. . Endothelial dysfunction and the risk of hypertension: the multi-ethnic study of atherosclerosis. Hypertension. (2010) 55:1210–6. 10.1161/HYPERTENSIONAHA.109.143123 - DOI - PMC - PubMed 5. 1. Moreno PR, Purushothaman KR, Fuster V, O'Connor WN. 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