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
Molecular Pharmacology
  • 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
Molecular Pharmacology

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 molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Vascular-Targeted Overexpression of G Protein-Coupled Receptor Kinase-2 in Transgenic Mice Attenuates β-Adrenergic Receptor Signaling and Increases Resting Blood Pressure

Andrea D. Eckhart, Tohru Ozaki, Hendrik Tevaearai, Howard A. Rockman and Walter J. Koch
Molecular Pharmacology April 2002, 61 (4) 749-758; DOI: https://doi.org/10.1124/mol.61.4.749
Andrea D. Eckhart
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tohru Ozaki
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hendrik Tevaearai
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Howard A. Rockman
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Walter J. Koch
1 2
  • 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

Cardiovascular regulation is tightly controlled by signaling through G protein-coupled receptors (GPCRs). β-Adrenergic receptors (ARs) are GPCRs that regulate inotropy and chronotropy in the heart and mediate vasodilation, which critically influences systemic vascular resistance. GPCR kinases (GRKs), including GRK2 (or βARK1), phosphorylate and desensitize agonist-activated βARs. Myocardial GRK2 levels are increased in heart failure and data suggest that vascular levels may also be elevated in hypertension. Therefore, we generated transgenic mice with vascular smooth muscle (VSM) targeted overexpression of GRK2, using a portion of the SM22α promoter, to determine its impact on vascular βAR regulation. VSM βAR signaling, as determined by adenylyl cyclase and mitogen-activated protein (MAP) kinase activation assays, was attenuated when GRK2 was overexpressed 2- to 3-fold. In vivo vasodilation in response to βAR stimulation using isoproterenol was attenuated and conscious resting mean arterial blood pressure was elevated from 96 ± 2 mm Hg in nontransgenic littermate control (NLC) mice (n = 9) to 112 ± 3 mm Hg and 117 ± 2 mm Hg in two different lines of SM22α-GRK2 transgenic mice (n = 7 and n = 5, respectively; p < 0.05). Interestingly, medial VSM thickness was increased 30% from 29.8 ± 1.6 μm in NLC mice (n = 6) to 39.4 ± 1.6 μm in SM22α-GRK2 mice (n = 7) (p < 0.05) and vascular GRK2 overexpression was sufficient to cause cardiac hypertrophy. These data indicate that we have developed a unique mouse model of hypertension, providing insight into the contribution that vascular βAR signaling makes toward resting blood pressure and overall cardiovascular regulation. Moreover, they suggest that GRK2 plays an important role in vascular control and may represent a novel therapeutic target for hypertension.

  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm 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

Molecular Pharmacology: 61 (4)
Molecular Pharmacology
Vol. 61, Issue 4
1 Apr 2002
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology 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.
Vascular-Targeted Overexpression of G Protein-Coupled Receptor Kinase-2 in Transgenic Mice Attenuates β-Adrenergic Receptor Signaling and Increases Resting Blood Pressure
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Vascular-Targeted Overexpression of G Protein-Coupled Receptor Kinase-2 in Transgenic Mice Attenuates β-Adrenergic Receptor Signaling and Increases Resting Blood Pressure

Andrea D. Eckhart, Tohru Ozaki, Hendrik Tevaearai, Howard A. Rockman and Walter J. Koch
Molecular Pharmacology April 1, 2002, 61 (4) 749-758; DOI: https://doi.org/10.1124/mol.61.4.749

Citation Manager Formats

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

Share
Research ArticleArticle

Vascular-Targeted Overexpression of G Protein-Coupled Receptor Kinase-2 in Transgenic Mice Attenuates β-Adrenergic Receptor Signaling and Increases Resting Blood Pressure

Andrea D. Eckhart, Tohru Ozaki, Hendrik Tevaearai, Howard A. Rockman and Walter J. Koch
Molecular Pharmacology April 1, 2002, 61 (4) 749-758; DOI: https://doi.org/10.1124/mol.61.4.749
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
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • The binding site for KCI807 in the androgen receptor
  • Fatty acid amide hydrolase in cisplatin nephrotoxicity
  • eCB Signaling System in hiPSC-Derived Neuronal Cultures
Show more Article

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 Molecular Pharmacology
  • 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
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics