ANTIHYPERTENSIVE AND CARDIOPROTECTIVE EFFECTS OF EPOXYEICOSATRIENOIC ACID ANALOGS AND SOLUBLE EPOXIDE HYDROLASE INHIBITORS (REVIEW).

In the present article is considered antihypertensive and cardioprotective action of epoxieicosatrienoic acids (EETs) analogues and soluble epoxide hydrolase (sEH) inhibitors. Being epoxygenase products of arachidonic acid metabolism EETs provide a wide spectrum of biological activity in different organs implicated in the regulation of arterial pressure, including vascular endothelium (VE), heart and kidney. EETs are acting as autocrine or paracrine agents producing vasodilation, reduction in salt and fluid retention. EETs exert vasodilatory properties by activation of the smooth muscle large conductance Ca2+ -activated K+ channels in different vascular beds. In experimental and clinical studies EETs provide beneficial influence in hypertensive states alleviating vascular endothelium function associated with reduction of inflammation and increased Na+ excretion, prevented cardiovascular and renal complications accompanied arterial hypertension (AH). In animals studies using Dahl-salt-sensitive (Dss) hypertensive rats EETs analogues displayed renoprotective effect, reducing mRNA expression of tumor growth factor-"B" as well as concomitant oxidative stress and fibrotic changes in the heart and kidneys. In cultered endothelial cells also was demonstrated anti-inflammatory action of EETs when they significantly decreased TNF-α-induced high level of monocyte chemoattractant protein-1, which was reversed by EETs antagonist. sEH is another new target for therapeutic intervention in cardiovascular diseases. In several experimental models of AH sEH inhibitors (sEHI) significantly reduce AP which was associated with their anti-inflammatory and renoprotective action. sEHI showed cardiovascular effect related to CYP2J2overexpression during myocardial ischemia-reperfusion injury. It should be noted that EETs demonstrate binding ability to PPAR receptor "Y" stimulating it's transcription process in endothelial cells facilitating by sEHI. It is suggested that EETs and sEH are involved in the regulation of the cardiovascular function playing significant role in vascular homeostasis.