Regulation of Oxygen Distribution in Tissues by Endothelial Nitric Oxide

Nitric oxide (NO) decreases cellular oxygen (O-2) consumption by competitively inhibiting cytochrome c oxidase. Here, we show that endogenously released endothelial NO, either basal or stimulated, can modulate O-2 consumption both throughout the thickness of conductance vessels and in the microcirculation. Furthermore, we have shown that such modulation regulates O-2 distribution to the surrounding tissues. We have demonstrated these effects by measuring O-2 consumption in blood vessels in a hypoxic chamber and O-2 distribution in the microcirculation using the fluorescent oxygen-probe Ru(phen)(3)(2+). 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 O-2, 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 O-2 throughout the vessel wall may be implicated in the origin of vascular pathologies such as atherosclerosis. (Circ Res. 2009;104:1178-1183.)