Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Immune Environment in Glioblastoma (Upcoming)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact

Submit a comment

Salt-sensitive hypertension in endothelin-B receptor–deficient rats
Cheryl E. Gariepy, … , James A. Richardson, Masashi Yanagisawa
Cheryl E. Gariepy, … , James A. Richardson, Masashi Yanagisawa
Published April 1, 2000
Citation Information: J Clin Invest. 2000;105(7):925-933. https://doi.org/10.1172/JCI8609.
View: Text | PDF
Article

Salt-sensitive hypertension in endothelin-B receptor–deficient rats

  • Text
  • PDF
Abstract

The role of the endothelin-B receptor (ETB) in vascular homeostasis is controversial because the receptor has both pressor and depressor effects in vivo. Spotting lethal (sl) rats carry a naturally occurring deletion in the ETB gene that completely abrogates functional receptor expression. Rats homozygous for this mutation die shortly after birth due to congenital distal intestinal aganglionosis. Genetic rescue of ETBsl/sl rats from this developmental defect using a dopamine-—hydroxylase (DBH)-ETB transgene results in ETB-deficient adult rats. On a sodium-deficient diet, DBH-ETB;ETBsl/sl and DBH-ETB;ETB+/+ rats both exhibit a normal arterial blood pressure, but on a high-sodium diet, the former are severely hypertensive. We find no difference in plasma renin activity or plasma aldosterone concentration between salt-fed wild-type, DBH-ETB;ETB+/+ or DBH-ETB;ETBsl/sl rats, and acute responses to intravenous L-NAME and indomethacin are similar between DBH-ETB;ETBsl/sl and DBH-ETB;ETB+/+ rats. Irrespective of diet, DBH-ETB;ETBsl/sl rats exhibit increased circulating ET-1, and, on a high-sodium diet, they show increased but incomplete hypotensive responses to acute treatment an ETA-antagonist. Normal pressure is restored in salt-fed DBH-ETB;ETBsl/sl rats when the epithelial sodium channel is blocked with amiloride. We conclude that DBH-ETB;ETBsl/sl rats are a novel single-locus genetic model of severe salt-sensitive hypertension. Our results suggest that DBH-ETB;ETBsl/sl rats are hypertensive because they lack the normal tonic inhibition of the renal epithelial sodium channel.

Authors

Cheryl E. Gariepy, Takashi Ohuchi, S. Clay Williams, James A. Richardson, Masashi Yanagisawa

×

Guidelines

The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.

  • Comments appear on the Journal’s website and are linked from the original article’s web page.
  • Authors are notified by email if their comments are posted.
  • The Journal reserves the right to edit comments for length and clarity.
  • No appeals will be considered.
  • Comments are not indexed in PubMed.

Specific requirements

  • Maximum length, 400 words
  • Entered as plain text or HTML
  • Author’s name and email address, to be posted with the comment
  • Declaration of all potential conflicts of interest (even if these are not ultimately posted); see the Journal’s conflict-of-interest policy
  • Comments may not include figures
This field is required
This field is required
This field is required
This field is required
This field is required
This field is required

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts