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RESEARCH PRODUCT

Regulation of Oxygen Distribution in Tissues by Endothelial Nitric Oxide

Cormac T. TaylorVictor M. VictorSalvador MoncadaPilar D'oconCristina NuñezJuan V. Esplugues

subject

Malemedicine.medical_specialtyNitric Oxide Synthase Type IIIEndotheliumPhysiologychemistry.chemical_elementOxygen consumptionBiologyNitric OxideOxygenMicrocirculationNitric oxideElectron Transport Complex IVRats Sprague-DawleyMicechemistry.chemical_compoundOxygen Consumption:CIENCIAS MÉDICAS ::Medicina interna [UNESCO]EnosInternal medicinemedicineAnimalsHumansCytochrome c oxidaseEndotheliumHypoxiaUNESCO::CIENCIAS MÉDICAS ::Medicina internaMice KnockoutNitric Oxide Synthase Type IIINitric oxide:CIENCIAS MÉDICAS [UNESCO]biology.organism_classificationRatsOxygenEndocrinologymedicine.anatomical_structurechemistryUNESCO::CIENCIAS MÉDICASCirculatory systemBiophysicsbiology.proteinNitric oxide ; Endothelium ; Oxygen consumptionEndothelium VascularCardiology and Cardiovascular MedicineSignal Transduction

description

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.

https://doi.org/10.1161/circresaha.109.197228