Regulation of Oxygen Distribution in Tissues by Endothelial Nitric Oxide

被引:60
|
作者
Victor, Victor M. [2 ,3 ,4 ]
Nunez, Cristina [3 ,4 ]
D'Ocon, Pilar [3 ,4 ]
Taylor, Cormac T. [5 ]
Esplugues, Juan V. [3 ,4 ]
Moncada, Salvador [1 ]
机构
[1] UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England
[2] Fdn Hosp Univ Doctor Peset, Valencia, Spain
[3] Univ Valencia, Fac Med, Dept Farmacol, E-46003 Valencia, Spain
[4] Univ Valencia, Fac Med, CIBERehd, E-46003 Valencia, Spain
[5] Univ Coll Dublin, Conway Inst, Dublin, Ireland
基金
爱尔兰科学基金会;
关键词
nitric oxide; endothelium; oxygen consumption; NO; NITROGLYCERIN; MITOCHONDRIA; CONSUMPTION; CELLS;
D O I
10.1161/CIRCRESAHA.109.197228
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.)
引用
收藏
页码:1178 / U121
页数:9
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