Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleCardiovascular

Role of Neuronal Nitric-Oxide Synthase in Estrogen-Induced Relaxation in Rat Resistance Arteries

Olga Lekontseva, Subhadeep Chakrabarti, Yanyan Jiang, Christopher C. Cheung and Sandra T. Davidge
Journal of Pharmacology and Experimental Therapeutics November 2011, 339 (2) 367-375; DOI: https://doi.org/10.1124/jpet.111.183798
Olga Lekontseva
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Subhadeep Chakrabarti
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yanyan Jiang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christopher C. Cheung
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sandra T. Davidge
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Estrogen has antihypertensive and vasorelaxing properties, partly via activation of endothelial nitric-oxide synthase (eNOS). Recently, neuronal nitric-oxide synthase (nNOS) has been detected in vascular cells, although the significance of this is unclear. Estrogen was found to stimulate nNOS in certain cultured cells. We hypothesized that estrogen regulates vascular tone partly via endothelium-derived nNOS. Human umbilical vein endothelial cells were used to test whether acute (5 min) stimulation with 17β-estradiol (E2) at 1 or 10 nM affected nNOS activity. Small mesenteric arteries from Sprague-Dawley rats were examined for relaxation to E2 (0.001–10 μM) in the absence or presence of selective nNOS inhibitor [N-propyl-l-arginine (l-NPA); 2 μM] or pan-NOS inhibitor [Nω-nitro-l-arginine methyl ester (l-NAME); 100 μM] using a wire myograph. Immunostaining was used to visualize nNOS in rat mesenteric artery cross-sections. Western blotting measured total and phospho-nNOS in endothelial cell lysates and thoracic aorta homogenates. E2 rapidly increased (p < 0.001) activating phosphorylation of nNOS and nitric oxide (NO) production (as measured by 4-amino-5-methylamino-2,7-difluorofluorescein fluorescence) in endothelial cells. Likewise, E2 caused dose-dependent relaxation of arteries from female rats, which was blunted by both l-NPA and l-NAME (p < 0.001). In contrast, E2 response was modest in male animals and unaffected by NOS inhibition. It is noteworthy that there was a greater baseline presence of phospho-nNOS in male relative to female aortas. Although eNOS is believed to be the main source of NO in the vascular endothelium, we confirmed nNOS expression in endothelial cells. Endothelial nNOS mediated E2 relaxation in isolated arteries from female animals. Altogether, these data suggest vascular nNOS as a novel mechanism in E2 signaling.

Footnotes

  • This study was supported by a grant from the Heart and Stroke Foundation of Alberta, Northwest Territories and Nunavut (to S.T.D.). O.L. is supported by an Alberta Heritage Foundation for Medical Research Doctoral Scholarship. S.C. is supported by a Fellowship from the Canadian Institutes for Health Research. C.C. was awarded an Alberta Heritage Foundation for Medical Research summer studentship. S.D. is funded by Alberta Innovates Health Solutions as an Alberta Heritage Foundation for Medical Research Scientist and is a Canada Research Chair, Tier 1 in Women's Cardiovascular Health.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.111.183798.

  • ABBREVIATIONS:

    eNOS
    endothelial nitric-oxide synthase
    CCRC
    cumulative concentration-response curve
    DAF-FM
    4-amino-5-methylamino-2,7-difluorofluorescein
    E2
    17β-estradiol
    ER
    estrogen receptor
    HUVEC
    human umbilical vein endothelial cell
    l-NPA
    N-propyl-l-arginine
    l-NAME
    Nω-nitro-l-arginine methyl ester
    MCh
    methacholine
    NA
    noradrenaline
    NO
    nitric oxide
    nNOS
    neuronal nitric-oxide synthase
    VSMC
    vascular smooth muscle cell
    vWF
    von Willebrand factor
    ANOVA
    analysis of variance
    RMANOVA
    repeated-measures ANOVA
    ICI 182780
    7α,17β-[9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol
    DAPI
    4,6-diamidino-2-phenylindole.

  • Received May 10, 2011.
  • Accepted July 29, 2011.
  • Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 339 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 339, Issue 2
1 Nov 2011
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Role of Neuronal Nitric-Oxide Synthase in Estrogen-Induced Relaxation in Rat Resistance Arteries
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleCardiovascular

nNOS and Estrogen in Vascular Function

Olga Lekontseva, Subhadeep Chakrabarti, Yanyan Jiang, Christopher C. Cheung and Sandra T. Davidge
Journal of Pharmacology and Experimental Therapeutics November 1, 2011, 339 (2) 367-375; DOI: https://doi.org/10.1124/jpet.111.183798

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleCardiovascular

nNOS and Estrogen in Vascular Function

Olga Lekontseva, Subhadeep Chakrabarti, Yanyan Jiang, Christopher C. Cheung and Sandra T. Davidge
Journal of Pharmacology and Experimental Therapeutics November 1, 2011, 339 (2) 367-375; DOI: https://doi.org/10.1124/jpet.111.183798
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Optimized S-nitrosohemoglobin Synthesis in Red Blood Cells
  • Exosomal miRNAs drive thrombosis in COVID-19
  • mitochondrial miRs in Fabry disease
Show more Cardiovascular

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics