Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • 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
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Spare guanylyl cyclase NO receptors ensure high NO sensitivity in the vascular system
Evanthia Mergia, … , Michael Russwurm, Doris Koesling
Evanthia Mergia, … , Michael Russwurm, Doris Koesling
Published June 1, 2006
Citation Information: J Clin Invest. 2006;116(6):1731-1737. https://doi.org/10.1172/JCI27657.
View: Text | PDF
Research Article Vascular biology

Spare guanylyl cyclase NO receptors ensure high NO sensitivity in the vascular system

  • Text
  • PDF
Abstract

In the vascular system, the receptor for the signaling molecule NO, guanylyl cyclase (GC), mediates smooth muscle relaxation and inhibition of platelet aggregation by increasing intracellular cyclic GMP (cGMP) concentration. The heterodimeric GC exists in 2 isoforms (α1-GC, α2-GC) with indistinguishable regulatory properties. Here, we used mice deficient in either α1- or α2-GC to dissect their biological functions. In platelets, α1-GC, the only isoform present, was responsible for NO-induced inhibition of aggregation. In aortic tissue, α1-GC, as the major isoform (94%), mediated vasodilation. Unexpectedly, α2-GC, representing only 6% of the total GC content in WT, also completely relaxed α1-deficient vessels albeit higher NO concentrations were needed. The functional impact of the low cGMP levels produced by α2-GC in vivo was underlined by pronounced blood pressure increases upon NO synthase inhibition. As a fractional amount of GC was sufficient to mediate vasorelaxation at higher NO concentrations, we conclude that the majority of NO-sensitive GC is not required for cGMP-forming activity but as NO receptor reserve to increase sensitivity toward the labile messenger NO in vivo.

Authors

Evanthia Mergia, Andreas Friebe, Oliver Dangel, Michael Russwurm, Doris Koesling

×

Figure 7

Systolic blood pressure in α-deficient mice.

Options: View larger image (or click on image) Download as PowerPoint
Systolic blood pressure in α-deficient mice.
(A) Systolic blood pressure...
(A) Systolic blood pressure as measured in conscious mice by tail-cuff plethysmography as described in Methods. Means (indicated by horizontal lines) of 111 and 104 mmHg were determined for the α1-KO mice and their WT siblings, respectively; for the α2-KO mice and the respective WT littermates, means of 111 and 110 mmHg were determined. The 95% confidence interval of the difference between α1-KO and WT mice is 1–15 mmHg. (B) Increase of blood pressure induced by l-NAME treatment of α1-KO mice (n = 5 per genotype). *P < 0.05, differences considered significant.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts