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The Difference Between Diseased And Normal Blood Vessels

 

 
Coronary heart disease and the many disorders that increase the risk of coronary heart disease (such as diabetes and high blood pressure) are associated with decreased blood flow to the muscles of the heart. One reason for this decreased blood flow is that blood vessels no longer respond to nitric oxide (NO), which binds a protein known as soluble guanylyl cyclase (sGC), triggering blood vessels to dilate. Drugs that are converted to NO in the body (and are therefore known as NO donors) have been used for many years to treat cardiovascular disease, but their effectiveness often rapidly decreases.

Now, Harald Schmidt and colleagues from Monash University, Australia, show in several animal models of cardiovascular disease and in human blood vessels from individuals with diabetes that a new drug (BAY 58-2667) can overcome one of the obstacles that leads to NO-donor ineffectiveness. In this study, which appears in the September issue of the Journal of Clinical Investigation, it is shown that the form of sGC found in diseased blood vessels differs from the sGC found in normal blood vessels and does not respond to NO. By contrast, activated sGC found in diseased blood vessels, but not sGC found in normal blood vessels, responded to BAY 58-2667 and triggered blood vessel dilation. This study might lead to the development of drugs that cause dilation of diseased blood vessels but not healthy ones.

In an accompanying commentary, Mark Gladwin discusses how this study raises many questions regarding the chemistry and mechanisms of NO-induced dilation of blood vessels.

TITLE: Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels

###

AUTHOR CONTACT:
Harald H. H. W. Schmidt
Monash University, Melbourne, Victoria, Australia.
E-mail: Harald.Schmidt@med.monash.edu.au.

Peter M. Schmidt
Monash University, Melbourne, Victoria, Australia.
E-mail: Peter.Schmidt@med.monash.edu.au.

View the PDF of this article at: http://https://www.the-jci.org/article.php?id=28371

ACCOMPANYING COMMENTARY

TITLE: Deconstructing endothelial dysfunction: soluble guanylyl cyclase oxidation and the NO resistance syndrome

AUTHOR CONTACT:
Mark T. Gladwin
National Institutes of Health, Bethesda, Maryland, USA.
E-mail: mgladwin@nih.gov.

View the PDF of this article at: http://https://www.the-jci.org/article.php?id=29807

JCI table of contents: September 1, 2006
CARDIOVASCULAR BIOLOGY: BAY 58-2667

Contact: Karen Honey
Journal of Clinical Investigation
 
 
 
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