Enzyme ENOS Plays Previously Unrecognized Role In Anaphylactic Shock

Anaphylaxis is a severe and rapid allergic reaction, and its most severe form - anaphylactic shock - can lead to death in minutes if left untreated. Anaphylactic shock can be caused by bee stings, food, medications, and latex exposure and one of the primary physical effects is dilation of blood vessels due to the production of nitric oxide (NO), resulting in dangerously low blood pressure. It is generally accepted that the enzyme inducible NO synthase (iNOS) is responsible for the excessive NO production during shock. However, in a study appearing in the August issue of the Journal of Clinical Investigation, Anje Cauwels and colleagues from Ghent University, Belgium, show that anaphylactic shock in mice was dependent entirely on NO produced not by iNOS, but by endothelial NO synthase (eNOS), which is made in endothelial cells that line blood vessels. The results show that eNOS is activated via the PI3K signaling pathway. The researchers went on to show that inhibition of NOS or PI3K, or eNOS deficiency provided complete protection against shock. The data strongly support the unexpected concept that eNOS-derived NO is the main cause of vessel dilation and low blood pressure in anaphylactic shock. In an accompanying commentary, Thomas Michel and Charles Lowenstein comment that, "these findings also suggest that inhibitors of PI3K…might plausibly be targets for the treatment of anaphylaxis."

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TITLE: Anaphylactic shock depends on PI3K and eNOS-derived NO

AUTHOR CONTACT:
Anje Cauwels
Ghent University and Flanders Interuniversity Institute for Biotechnology, Ghent, Belgium.
E-mail: Anje.Cauwels@dmbr.UGent.be.

View the PDF of this article at: http://https://www.the-jci.org/article.php?id=25426

ACCOMPANYING COMMENTARY

TITLE: What's in a name? eNOS and anaphylactic shock

AUTHOR CONTACT:
Thomas Michel
Harvard Medical School, Boston, Massachusetts, USA.
Emal: tmichel@research.bwh.harvard.edu.

OR

Charles J. Lowenstein
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Email: clowenst@jhmi.edu.

View the PDF of this article at: http://https://www.the-jci.org/article.php?id=29406

Source: JCI table of contents: August, 2006

Contact: Brooke Grindlinger
Journal of Clinical Investigation