title: Regulation of oxygen distribution in tissues by endothelial nitric oxide.
abstract: 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.
authors.affiliation: Fundación Hospital Universitario Doctor Peset, Valencia, Spain.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Victor
authors.forename: Cristina
authors.initials: C
authors.lastname: Nuñez
authors.forename: Pilar
authors.initials: P
authors.lastname: D'Ocón
authors.forename: Cormac T
authors.initials: CT
authors.lastname: Taylor
authors.forename: Juan V
authors.initials: JV
authors.lastname: Esplugues
authors.forename: Salvador
authors.initials: S
authors.lastname: Moncada
mesh_terms: D000818:Animals; D003576:Electron Transport Complex IV / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D003576:Electron Transport Complex IV; D010100:Oxygen