Renal And Cardiovascular Actions Of 20‐Hydroxyeicosatetraenoic Acid And Epoxyeicosatrienoic Acids

Abstract

4. In summary, the available evidence indicates that CYP metabolites of AA play a central role in the regulation of renal, pulmonary and vascular function and that abnormalities in this system may contribute to the pathogenesis of cardiovascular diseases.

Role of epoxyeicosatrienoic acids in protecting the myocardium following ischemia/reperfusion injury

“…For example, EETs have potent vasodilatory properties [37] and 20-hydroxyeicosatetraenoic acid (20-HETE) has potent vasoconstrictive effects [38]. Therefore, changes in the expression and/or activity of specific CYP epoxygenase and hydroxylase enzymes can alter the delicate balance between EETs and 20-HETE.…”

“…K Ca channels can be activated by elevations in intracellular Ca 2+ and membrane depolarization [65,66]. CYP epoxygenase derived EETs are known activators of BK Ca channels in vascular smooth muscle [20,67], whereas, CYP ω-hydroxylases derived HETEs are known inhibitors in vascular smooth muscle [38,68,69]. Recent evidence suggests that newly identified K Ca channels in cardiac mitochondria (mito K Ca ) [53,70] are important mediators of cardioprotection.…”

“…While it is very likely that signaling pathways involved in EET-mediated cardioprotection target the mitochondria, it is unknown whether the response involves transient opening of mPTP prior to ischemia or prevents prolonged opening during reperfusion. EETs have been shown to activate sarc K ATP [30,61] and mito K ATP channels [31] in the heart, and K Ca channels [20,67], in vascular smooth muscle cells [38,68,69]. Increased flavoprotein fluorescence in CYP2J2 Tr cardiomyocytes and wild type cardiomyocytes treated with EETs [31], strongly suggest convergence of a cardioprotective signal onto the mitochondria.…”

CytochromeP-450-dependent metabolism of arachidonic acid in the kidney of rats with diabetes insipidus

“…Inhibition of the synthesis of 20-HETE attenuates the vasoconstrictor response of renal arterioles to elevations in transmural pressure in vitro (16, 18) and autoregulation of renal blood flow and tubuloglomerular feedback responses in vivo (8,48). At the level of the renal tubules, 20-HETE inhibits sodium reabsorption in the proximal tubule and thick ascending limb of the loop of Henle (6,32,34,39).Previous studies indicated that the renal production of EETs and/or 20-HETE is altered in diabetes and in genetic and experimental models of hypertension (1,7,21,24,25,28,41). The release of 20-HETE in renal and peripheral blood vessels is stimulated by ANG II (5), phenylephrine (20a), endothelin (37), and serotonin (3).…”

“…Previous studies indicated that the renal production of EETs and/or 20-HETE is altered in diabetes and in genetic and experimental models of hypertension (1,7,21,24,25,28,41). The release of 20-HETE in renal and peripheral blood vessels is stimulated by ANG II (5), phenylephrine (20a), endothelin (37), and serotonin (3).…”