Roles of Renal Cytochrome P450-Dependent Arachidonic Acid Metabolites in Hypertension.

Omata, Ken; Abe, Keishi; Sheu, Hsu-Lang; Yoshida, Kazunori; Tsutsumi, Eishi; Yoshinaga, Kaoru; Abraham, Nader G.; Laniado−Schwartzman, Michal

doi:10.1620/tjem.166.93

Cited by 20 publications

(13 citation statements)

References 40 publications

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“…20-HETE then may contribute to pressure natriuresis by inhibiting both Na ϩ -K ϩ -ATPase activity and Na ϩ /H ϩ exchange, whereas EETs would be expected to act by inhibiting the Na ϩ /H ϩ exchanger alone. The view that 20-HETE and/or EETs contribute to pressure natriuresis is consistent with the large body of evidence indicating that the formation of these compounds is altered in genetic and experimental animal models of hypertension (1,26,29,47,50,51,63,(67)(68)(69)71). It also fits with previous findings that inhibitors of the renal formation of 20-HETE and/or EETs promote the development of salt-sensitive hypertension in normotensive strains of rats (25,67), that increasing the renal formation of 20-HETE with clofibrate or tempol lowers blood pressure in Dahl S rats (26,63,71), and that increasing renal levels of EETs with soluble epoxide hydrolase inhibitors lowers blood pressure in spontaneously hypertensive (77) and ANG II-hypertensive rats (27).…”

Section: Discussionsupporting

confidence: 79%

“…Given the similarities between the effects of EETs and 20-HETE on Na ϩ transport and those produced by elevations in RPP, these observations suggest that EETs and/or 20-HETE may serve as mediators of pressure natriuresis if elevations in RPP and/or RIHP stimulate the formation and/or release of these compounds in the kidney. This hypothesis is also consistent with a large body of evidence indicating that the renal formation of EETs and 20-HETE is altered in hypertension (1,50,51,68,69) and that chronic induction (1,71) or blockade (1,25,67,69) of this pathway alters blood pressure in both normotensive and hypertensive animals.…”

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confidence: 89%

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Inhibition of the formation of EETs and 20-HETE with 1-aminobenzotriazole attenuates pressure natriuresis

Santos

Dahly-Vernon

Hoagland

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

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/ajpregu. 00713.2003.-This study examined the effects of chronic blockade of the renal formation of epoxyeicosatrienoic acids and 20-hydroxyeicosatetraenoic acid with 1-aminobenzotriazole (ABT; 50 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ip for 5 days) on pressure natriuresis and the inhibitory effects of elevations in renal perfusion pressure (RPP) on Na ϩ -K ϩ -ATPase activity and the distribution of the sodium/hydrogen exchanger (NHE)-3 in the proximal tubule of rats. In control rats (n ϭ 15), sodium excretion rose from 2.3 Ϯ 0.4 to 19.4 Ϯ 1.8 eq ⅐ min Ϫ1 ⅐ g kidney weight Ϫ1 when RPP was increased from 114 Ϯ 1 to 156 Ϯ 2 mmHg. Fractional excretion of lithium rose from 28 Ϯ 3 to 43 Ϯ 3% of the filtered load. Chronic treatment of the rats with ABT for 5 days (n ϭ 8) blunted the natriuretic response to elevations in RPP by 75% and attenuated the increase in fractional excretion of lithium by 45%. In vehicle-treated rats, renal Na ϩ -K ϩ -ATPase activity fell from 31 Ϯ 5 to 19 Ϯ 2 mol Pi ⅐ mg protein Ϫ1 ⅐ h Ϫ1 and NHE-3 protein was internalized from the brush border of the proximal tubule after an elevation in RPP. In contrast, Na ϩ -K ϩ -ATPase activity and the distribution of NHE-3 protein remained unaltered in rats treated with ABT. These results suggest that cytochrome P-450 metabolites of arachidonic acid contribute to pressure natriuresis by inhibiting Na ϩ -K ϩ -ATPase activity and promoting internalization of NHE-3 protein from the brush border of the proximal tubule. 20-hydroxyeicosatetraenoic acid; epoxyeicosatrienoic acids; sodium/ hydrogen exchanger-3; sodium-potassium-adenosinetriphosphatase; kidney; proximal tubule; renal hemodynamics THE CONCEPT THAT THE KIDNEY plays an important role in the long-term control of arterial pressure is based on the phenomenon of pressure natriuresis (19,21). Despite intensive investigation, many aspects of the mechanism of pressure natriuresis remain unknown. Previous studies have indicated that pressure natriuresis is associated with elevations in renal medullary blood flow (13, 59 -61) and renal interstitial hydrostatic pressure (RIHP) (15,19,31). Na ϩ transport in the proximal tubule (22,32,33,57,76) and the loop of Henle (34, 57) decreases after elevations in renal perfusion pressure (RPP). Increases in RPP have been proposed to inhibit Na ϩ transport in the proximal tubule by increasing backflux of Na ϩ through the paracellular pathway (14,19,36). However, this mechanism seems unlikely because of the lack of an electrochemical gradient for backdiffusion of Na ϩ in the proximal tubule, and the existing Cl Ϫ gradient favors reabsorption rather than backleak. The work of Magyar et al. (37,38) and others (72,74,75,76,78,79), indicating that elevations in RPP are associated with a fall in Na ϩ -K ϩ -ATPase activity and internalization of the sodium/hydrogen exchanger (NHE)-3 from the brush border of the proximal tubule, has led to the suggestion that some signal-transduction pathway probably couples elevations in RPP to inhibition of the active transport of Na ϩ in the proximal tubule. H...

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Section: Discussionsupporting

confidence: 79%

supporting

confidence: 89%

Inhibition of the formation of EETs and 20-HETE with 1-aminobenzotriazole attenuates pressure natriuresis

Santos

Dahly-Vernon

Hoagland

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

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“…CYP2J11, like CYP2J5, is expressed in the kidney, is localized to the renal proximal convoluted tubules, and is active in the metabolism of AA to EETs, primarily 14,15-EET. Renal proximal tubules and collecting ducts have high levels of EETs (Omata et al, 1992). Together, this suggests that CYP2J11 products may also help moderate fluid/electrolyte transport in the kidney.…”

Section: Discussionmentioning

confidence: 96%

Characterization of Four New Mouse Cytochrome P450 Enzymes of the CYP2J Subfamily

et al. 2013

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The cytochrome P450 superfamily encompasses a diverse group of enzymes that catalyze the oxidation of various substrates. The mouse CYP2J subfamily includes members that have wide tissue distribution and are active in the metabolism of arachidonic acid (AA), linoleic acid (LA), and other lipids and xenobiotics. The mouse Cyp2j locus contains seven genes and three pseudogenes located in a contiguous 0.62 megabase cluster on chromosome 4. We describe four new mouse CYP2J isoforms (designated CYP2J8, CYP2J11, CYP2J12, and CYP2J13). The four cDNAs contain open reading frames that encode polypeptides with 62-84% identity with the three previously identified mouse CYP2Js. All four new CYP2J proteins were expressed in Sf21 insect cells. Each recombinant protein metabolized AA and LA to epoxides and hydroxy derivatives. Specific antibodies, mRNA probes, and polymerase chain reaction primer sets were developed for each mouse CYP2J to examine their tissue distribution. CYP2J8 transcripts were found in the kidney, liver, and brain, and protein expression was confirmed in the kidney and brain (neuropil). CYP2J11 transcripts were most abundant in the kidney and heart, with protein detected primarily in the kidney (proximal convoluted tubules), liver, and heart (cardiomyocytes). CYP2J12 transcripts were prominently present in the brain, and CYP2J13 transcripts were detected in multiple tissues, with the highest expression in the kidney. CYP2J12 and CYP2J13 protein expression could not be determined because the antibodies developed were not immunospecific. We conclude that the four new CYP2J isoforms might be involved in the metabolism of AA and LA to bioactive lipids in mouse hepatic and extrahepatic tissues.

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“…The CYP2J2-mediated increase in EET increases fatty acid oxidation and adiposity [17,27,28]. Although EETs exhibit potent biological effects, including vasodilatation and inhibition of the inflammatory response [4,29,30] and in adiposity [17,27,28], their influence on mitochondrial function and proliferatoractivated receptor gamma coactivator-1a (PGC-1a) in relation to adipogenesis remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Epoxyeicosatrienoic Acids Regulate Adipocyte Differentiation of Mouse 3T3 Cells, Via PGC-1α Activation, Which Is Required for HO-1 Expression and Increased Mitochondrial Function

Waldman

Bellner

Vanella

et al. 2016

Stem Cells and Development

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Epoxyeicosatrienoic acid (EET) contributes to browning of white adipose stem cells to ameliorate obesity/ diabetes and insulin resistance. In the current study, we show that EET altered preadipocyte function, enhanced peroxisome proliferation-activated receptor g coactivator a (PGC-1a) expression, and increased mitochondrial function in the 3T3-L1 preadipocyte subjected to adipogenesis. Cells treated with EET resulted in an increase, P < 0.05, in PGC-1a and a decrease in mitochondria-derived ROS (MitoSox), P < 0.05. The EET increase in heme oxygenase-1 (HO-1) levels is dependent on activation of PGC-1a as cells deficient in PGC-1a (PGC-1a knockout adipocyte cell) have an impaired ability to express HO-1, P < 0.02. Additionally, adipocytes treated with EET exhibited an increase in mitochondrial superoxide dismutase (SOD) in a PGC-1a-dependent manner, P < 0.05. The increase in PGC-1a was associated with an increase in b-catenin, P < 0.05, adiponectin expression, P < 0.05, and lipid accumulation, P < 0.02. EET decreased heme levels and mitochondria-derived ROS (MitoSox), P < 0.05, compared to adipocytes that were untreated. EET also decreased mesoderm-specific transcript (MEST) mRNA and protein levels (P < 0.05). Adipocyte secretion of EET act in an autocrine/ paracrine manner to increase PGC-1a is required for activation of HO-1 expression. This is the first study to dissect the mechanism by which the antiadipogenic and anti-inflammatory lipid, EET, induces the PGC-1a signaling cascade and reprograms the adipocyte phenotype by regulating mitochondrial function and HO-1 expression, leading to an increase in healthy, that is, small, adipocytes and a decrease in adipocyte enlargement and terminal differentiation. This is manifested by an increase in mitochondrial function and an increase in the canonical Wnt signaling cascade during adipocyte proliferation and terminal differentiation.

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Roles of Renal Cytochrome P450-Dependent Arachidonic Acid Metabolites in Hypertension.

Cited by 20 publications

References 40 publications

Inhibition of the formation of EETs and 20-HETE with 1-aminobenzotriazole attenuates pressure natriuresis

Inhibition of the formation of EETs and 20-HETE with 1-aminobenzotriazole attenuates pressure natriuresis

Characterization of Four New Mouse Cytochrome P450 Enzymes of the CYP2J Subfamily

Epoxyeicosatrienoic Acids Regulate Adipocyte Differentiation of Mouse 3T3 Cells, Via PGC-1α Activation, Which Is Required for HO-1 Expression and Increased Mitochondrial Function

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