engleski

Role of metabolites of arachidonic acid in regulation of vascular function

Eicosanoids, metabolites of arachidonic acid (AA), are crucial in maintenance of vascular tone and reactivity to various physiological stimuli, contributing to blood pressure regulation, appropriate tissue perfusion, and protection of, or susceptibility to atherosclerosis and thrombosis.While the importance of prostaglandin (PGs)/TX balance is well documented, there is an increasing body of evidence that hydroxylation or epoxygenation of AA via CYP450 enzymes significantly contribute to physiological maintenance of vascular tone and vascular reactivity of resistance vessels.20-HETE mediates arterial myogenic constriction and arteriolar response to increased pO2 in vitro and the autoregulation of cerebral blood flow in vivo. On the other hand, increased levels of 20-HETE mediates cerebral microvessels’ vasoconstriction and increases tissue damage after stroke in rats and in human, while increasing levels of EETs or decreasing levels of 20-HETE have beneficial effects.EETs are anti-inflammatory, sustain endothelium-dependent vasodilation in human essential hypertension, and decreased EETs are associated with salt-sensitive hypertension. The increased production of reactive oxygen species (ROS) underlies disbalance of vasodilator vs. vasoconstrictor eicosanoids. ROS are generated by a variety of enzymes in vascular tissues, but also in circulating and adhering leukocytes.There is a circuitous relationship between ROS and cyclooxygenases (COX1, 2) upregulating each other. 20-HETE significantly increases vascular production of ROS. ROS mediate non-enzymatic peroxidation of AA, which gives rise to isoprostanes, particularly to potent vasoconstrictors, 8-epi-PGF2α and 8-epi-PGE2. In oxidative stress, blood levels of isoprostanes are much higher than those of COXs’ products. In conclusion, there is a communication network among various eicosanoids. In physiological conditions eicosanoids are important in maintenance of vascular tone and reactivity, but in condition with increased ROS/isoprotanes formation, the imbalance of the PGI2/TXA2 system and/or in 20HETE/EETs system can occur, which may become deleterious to vascular function, such as in stroke and hypertension.

arachidonic acid; vascular function; EETs; 20-HETE

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