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Circulation Research. 2009;104:1178-1183
Published online before print April 30, 2009, doi: 10.1161/CIRCRESAHA.109.197228
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(Circulation Research. 2009;104:1178.)
© 2009 American Heart Association, Inc.


Molecular Medicine

Regulation of Oxygen Distribution in Tissues by Endothelial Nitric Oxide

Victor M. Victor, Cristina Nuñez, Pilar D'Ocón, Cormac T. Taylor, Juan V. Esplugues*, Salvador Moncada*

From the Fundación Hospital Universitario Doctor Peset (V.M.V.), Valencia, Spain; Departamento de Farmacología and CIBERehd (V.M.V., C.N., P.D., J.V.E.), Facultad de Medicina, Universidad de Valencia, Spain; University College Dublin Conway Institute (C.T.T.), Ireland; and Wolfson Institute for Biomedical Research (S.M.), University College London, United Kingdom.

Correspondence to Prof S. Moncada, The Wolfson Institute for Biomedical Research, University College London, Gower St, London WC1E 6BT, United Kingdom. E-mail s.moncada{at}ucl.ac.uk

Nitric oxide (NO) decreases cellular oxygen (O2) consumption by competitively inhibiting cytochrome c oxidase. Here, we show that endogenously released endothelial NO, either basal or stimulated, can modulate O2 consumption both throughout the thickness of conductance vessels and in the microcirculation. Furthermore, we have shown that such modulation regulates O2 distribution to the surrounding tissues. We have demonstrated these effects by measuring O2 consumption in blood vessels in a hypoxic chamber and O2 distribution in the microcirculation using the fluorescent oxygen-probe Ru(phen)32+. Removal of NO by physical or pharmacological means, or in eNOS–/– mice, abolishes this regulatory mechanism. Our results indicate that, in addition to its well-known effect on the regulation of vascular tone, endothelial NO plays a major role in facilitating the distribution of O2, an action which is crucial for the adaptation of tissues, including the vessel wall itself, to hypoxia. It is possible that changes in the distribution of O2 throughout the vessel wall may be implicated in the origin of vascular pathologies such as atherosclerosis.


Key Words: nitric oxide • endothelium • oxygen consumption


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The Ligand Binding Battle at Cytochrome c Oxidase: How NO Regulates Oxygen Gradients in Tissue
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Circ. Res. 2009 104: 1136-1138. [Extract] [Full Text] [PDF]



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