doi: 10.1161/CIRCRESAHA.108.183442
© 2008 American Heart Association, Inc.
Editorials |
Transnitrosation Signals Oxyhemoglobin Desaturation
From the Division of Pediatric Respiratory Medicine (N.M., B.G.), University of Virginia School of Medicine, Charlottesville; and Department of Pediatric Critical Care (A.D.), Washington University School of Medicine, St Louis, Mo.
Correspondence to Benjamin Gaston, MD, Box 800386, University of Virginia School of Medicine, Charlottesville, VA 22908. E-mail bmg3g@virginia.edu
See related article, pages 545–553
Key Words: S-nitrosylation • hypoxia • blood flow
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Erythrocytes dilate peripheral blood vessels as a function of oxyhemoglobin desaturation.1 This effect increases regional blood flow to hypoxic tissues. The mechanisms underlying the peripheral vasodilatory effects of desaturating erythrocytes are incompletely understood but do not involve activation of local, endothelial NO synthase (eNOS). Indeed, eNOS-derived NO itself primarily relaxes large vessels and does that primarily only in the absence of blood.
In this issue of Circulation Research, Diesen et al confirm that thiols carrying a nitrosonium (NO+) equivalent signal cyclic GMP-dependent vascular smooth muscle relaxation during erythrocytic oxyhemoglobin desaturation.2 These data support paradigm-changing work demonstrating that nitrogen oxides are transported by circulating erythrocytes to signal oxyhemoglobin desaturation through serial NO/NO+ thiol equilibria and transfer reactions (transnitrosation) and that these reactions normally take place at sites remote from NOS activity.1–3 These new data show clearly that this signaling is independent of local NOS activity, of cyclooxygenase, of ATP, and of the effects of hypoxia itself on vascular smooth muscle.
Erythrocytes are endogenously "preloaded" with nitrogen oxides for delivery to vessels in conditions of oxyhemoglobin desaturation.1–3 This signaling links delivery of erythrocytic NO/NO+ groups to oxyhemoglobin desaturation, permitting augmented blood flow to hypoxic tissue. Three mechanisms have been proposed by which transitions in hemoglobin (Hb) conformation may result in nitrogen oxide transfer to blood vessels. (1) In the originally proposed mechanism, Hb deoxygenation (R-to-T transition) permits transnitrosation from Hb β-chain cysteine 93 (βCys93) to erythrocytic carrier thiols (Figure).1–3 This concept is supported by the data obtained by
Related Article:
Circ. Res. 2008 103: 545-553.