Naslov
Metabolites of arachidonic acid and endothelial function in hypertension

Autori
Drenjančević, Ines

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
Abstract book / - Beograd, 2014, 7-7

Skup
7th Central EUropean meeting on hypertension and 4th Serbian society of hypertension meeting

Mjesto i datum
Beograd, Srbija, 20.03.2014. - 23.03.2014

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
arachidonic acid; cyp450 pathway; endothelial dysfunction; isoprostanes
(Metabolites of arachidonic acid and endothelial function in hypertension)

Sažetak
Arachidonic acid (AA), a cell membrane phospholipid is a precursor of important eicosanoids, which regulate systemic blood pressure and thrombogenesis. AA can be metabolized via enzymatic and non-enzymatic pathways: enzymatically via cyclooxygenases to prostaglandins and thromboxane ; lypooxygenases form various forms of leukotrienes and CYP450-4A enzymes produce epoxyeicosatrienoic acids (EETs) and/or 20-hydroxyeicosatetraenoic acid (20-HETE), all of which can affect endothelium-dependant mechanisms of vascular reactivity to various stimuli, leading to vasoconstriction or vasodilation and contribute to etiopathogenesis of hypertension. It is well known that balance between vasodilator prostaglandins (e.g.PGI2) and thromboxane A2 has significant role in vascular tone regulation and susceptibility to atherosclerosis. Recently, attention is drawn to CYP450-4A metabolites of AA which have been demonstrated as potent vasoactive metabolites and related to development of endothelial dysfunction and experimental and human hypertension. Imbalance of vasoactive eicosanoids also leads to ischemia, thrombosis, coagulopathy, myocardial infarction, and stroke. Non-enzymatic metabolism of AA occurs by reactive oxygen species (ROS)-mediated peroxidation, which gives rise to the isoprostanes, particularly to potent vasoconstrictors, 8-epi-PGF2α and 8-epi-PGE2. During oxidative stress, blood levels of isoprostanes are much higher than those of cyclooxygenase products. Isoprostanes can activate cell signaling pathways and cellular responses. Urinary isoprostane levels are used as biomarkers of oxidative stress in ischemic-reperfusion injury, atherosclerosis, and hepatic diseases. Novel data show an association between increased CYP4A activity and oxidative stress in human subjects with hypertension. Increased urinary 20-HETE excretion correlated positively with markers of oxidative stress, including F2-isoprostanes, and with elevated BP. Similarly, patients recovering from acute ischemic stroke have increased plasma 20-HETE concentrations and elevated plasma F2-isoprostane levels compared with healthy controls. An accumulated body of evidence suggests that there is a cross-talk between 20-HETE and ROS production in response to flow- and pressure-induced stimuli, in human and experimental animal microcirculation. All of presented suggest that there is a communication network among various eicosanoids. In physiological conditions eicosanoids are important in maintenance of vascular tone and reactivity, but with imbalance in the PGI2/TXA2 system and/or in chronic activation of CYP4A/20HETE system or lack of EETs and high oxidative stress they become deleterious to endothelial function and blood pressure regulation.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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