期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 297, 期 2, 页码 H495-H507出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00349.2009
关键词
endothelium-derived hyperpolarizing factors; vascular relaxation; 15-lipoxygenase; 12-lipoxygenase; trihydroxyeicosatrienoic acids; hydroxyepoxyeicosatrienoic acids
资金
- National Heart, Lung, and Blood Institute [HL-37981]
- American Heart Association
Chawengsub Y, Gauthier KM, Campbell WB. Role of arachidonic acid lipoxygenase metabolites in the regulation of vascular tone. Am J Physiol Heart Circ Physiol 297: H495-H507, 2009. First published June 12, 2009; doi:10.1152/ajpheart.00349.2009.-Stimulation of vascular endothelial cells with agonists such as acetylcholine (ACh) or bradykinin or with shear stress activates phospholipases and releases arachidonic acid (AA). AA is metabolized by cyclooxygenases, cytochrome P-450s, and lipoxygenases (LOs) to vasoactive products. In some arteries, a substantial component of the vasodilator response is dependent on LO metabolites of AA. Nitric oxide (NO)- and prostaglandin (PG)-independent vasodilatory responses to ACh and AA are reduced by inhibitors of LO and by antisense oligonucleotides specifically against 15-LO-1. Vasoactive 15-LO metabolites derived from the vascular endothelium include 15-hydroxy-11, 12-epoxyeicosatrienoic acid (15-H-11, 12-HEETA) that is hydrolyzed by soluble epoxide hydrolase to 11, 12, 15-trihydroxyeicosatrienoic acid (11, 12, 15-THETA). HEETA and THETA are endothelium-derived hyperpolarizing factors that induce vascular relaxations by activation of smooth muscle apamin-sensitive, calcium-activated, small-conductance K+ channels causing hyperpolarization. In other arteries, the 12-LO metabolite 12-hydroxyeicosatetraenoic acid is synthesized by the vascular endothelium and relaxes smooth muscle by large-conductance, calcium-activated K+ channel activation. Thus formation of vasodilator eicosanoids derived from LO pathways contributes to the regulation of vascular tone, local blood flow, and blood pressure.
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