The link between hemoglobin, NO production, and vasodilation
Hypoxic vasodilation is a fundamental physiological process that ensures that tissues receive adequate blood flow and oxygen delivery during respiration and metabolic stress. Although this process has been appreciated for many decades, the identity of the oxygen sensor and the mechanism of vasodilation remain uncertain.
In a study appearing online on July 21 in advance of print publication of the August 1 issue of the Journal of Clinical Investigation, Mark Gladwin and colleagues from the National Heart, Lung, and Blood Institute present biochemical data supporting a novel function for hemoglobin as a nitrite reductase, which generates nitric oxide (NO). Hemoglobin's enzymatic activity is highest when it is 40-60% saturated with oxygen, an ideal set point for NO generation during hypoxia. This proposed mechanism for NO formation is suited for regulating hypoxic vasodilation under a variety of physiological and pathological ranges of temperature and pH.
These studies support a novel role for hemoglobin and further unravel the mechanism of the nitrite-hemoglobin reaction. Understanding this chemistry may aid development of therapies that target NO delivery to tissues under hypoxic stress using nitrite solutions.
Title: Enzymatic Function of Hemoglobin as a Nitrite Reductase that Produces Nitric Oxide under Allosteric Control
AUTHOR CONTACT:
Mark T. Gladwin
NHLBI/NIH, Bethesda, MD USA
Phone: 301-435-2310; Fax: 301-451-7091; E-mail: mgladwin@mail.nih.gov
View the PDF of this article at: https://www.the-jci.org/article.php?id=24650
IMMUNOLOGY
Biting into the mechanisms of oral tolerance
In a study appearing online on July 21 in advance of print pu
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Contact: Stacie Bloom
press_releases@the-jci.org
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Journal of Clinical Investigation
21-Jul-2005