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
OtherCARDIOVASCULAR PHARMACOLOGY

PST2238: A New Antihypertensive Compound That Antagonizes the Long-Term Pressor Effect of Ouabain

P. Ferrari, L. Torielli, M. Ferrandi, G. Padoani, L. Duzzi, M. Florio, F. Conti, P. Melloni, L. Vesci, N. Corsico and G. Bianchi
Journal of Pharmacology and Experimental Therapeutics April 1998, 285 (1) 83-94;
P. Ferrari
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
L. Torielli
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Ferrandi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G. Padoani
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
L. Duzzi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Florio
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
F. Conti
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
P. Melloni
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
L. Vesci
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
N. Corsico
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G. Bianchi
  • 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

The inhibition of the long-term pressor effect of ouabain may be useful for the therapy of essential hypertension. Here, for the first time, a selective inhibitor of the ouabain pressor effect is described.In vitro, 17β-(3-furyl)-5β-androstane-3β, 14β, 17α-triol (PST 2238) displaced ouabain from its binding sites on purified sodium, potassium ATPase enzyme (Na-K ATPase) (IC50 1.7 × 10−6 M) without interacting with other receptors involved in blood pressure regulation or hormonal control. In cultured renal cells, incubation with ouabain (10−10 to 10−8 M) for 5 days stimulated the Na-K pump at Vmax, whereas PST 2238 showed the same effect at micromolar concentration. The ouabain-dependent increase in the Na-K pump rate was abolished by PST 2238 at concentrations from 10−14 to 10−9 M. In rats made hypertensive by chronic infusion of 50 μg/kg/day of ouabain, PST 2238 given p.o at very low doses (0.1–1 μg/kg/day for 4 weeks) abolished the increase in blood pressure and renal Na-K ATPase activity caused by ouabain. PST 2238 did not affect either blood pressure or renal Na-K ATPase activity in normotensive rats. In conclusion, PST 2238 is a very potent compound that normalizes both blood pressure and alterations in the Na-K pump caused by ouabain. Thus it represents the prototype of a new class of antihypertensive drugs that could be effective in forms of hypertension sustained by the concomitant increase of endogenous ouabain levels and alterations in the Na-K pump.

Footnotes

  • Send reprint requests to: Patrizia Ferrari, Prassis Istituto Ricerche Sigma-Tau, via Forlanini 3, 20019 Settimo Milanese (Milano), Italy.

  • Abbreviations:
    CS
    control-saline rats
    DBP
    diastolic blood pressure
    DMSO
    dimethylsulfoxide
    MBP
    mean blood pressure
    NRK cells
    normal rat kidney cells
    OLF
    ouabain-like factor
    OS
    ouabain-sensitive rats
    SBP
    systolic blood pressure
    SDS
    sodium dodecylsulfate
    • Received May 15, 1997.
    • Accepted December 18, 1997.
  • 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
Vol. 285, Issue 1
1 Apr 1998
  • Table of Contents
  • Index by author
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.
PST2238: A New Antihypertensive Compound That Antagonizes the Long-Term Pressor Effect of Ouabain
(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
OtherCARDIOVASCULAR PHARMACOLOGY

PST2238: A New Antihypertensive Compound That Antagonizes the Long-Term Pressor Effect of Ouabain

P. Ferrari, L. Torielli, M. Ferrandi, G. Padoani, L. Duzzi, M. Florio, F. Conti, P. Melloni, L. Vesci, N. Corsico and G. Bianchi
Journal of Pharmacology and Experimental Therapeutics April 1, 1998, 285 (1) 83-94;

Citation Manager Formats

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

Share
OtherCARDIOVASCULAR PHARMACOLOGY

PST2238: A New Antihypertensive Compound That Antagonizes the Long-Term Pressor Effect of Ouabain

P. Ferrari, L. Torielli, M. Ferrandi, G. Padoani, L. Duzzi, M. Florio, F. Conti, P. Melloni, L. Vesci, N. Corsico and G. Bianchi
Journal of Pharmacology and Experimental Therapeutics April 1, 1998, 285 (1) 83-94;
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
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • TAS-301, an Inhibitor of Smooth Muscle Cell Migration and Proliferation, Inhibits Intimal Thickening after Balloon Injury to Rat Carotid Arteries
  • Identification of Low Molecular Weight GP IIb/IIIa Antagonists That Bind Preferentially to Activated Platelets
  • Differential Contribution of Angiotensinergic and Cholinergic Receptors in the Hypothalamic Paraventricular Nucleus to Osmotically Induced AVP Release
Show more CARDIOVASCULAR PHARMACOLOGY

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