20-Hydroxyeicosa-tetraenoic acid (20 HETE) activates protein kinase C. Role in regulation of rat renal Na+,K+-ATPase.

Nowicki, Susana; Chen, S L; Aizman, Oleg; Cheng, Xian-Jun; Li, D; Nowicki, Cristina; Nairn, Angus C.; Greengard, Paul; Aperia, Anita

doi:10.1172/jci119279

Cited by 148 publications

(106 citation statements)

References 44 publications

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“…proximal tubular S2 and S3 segments), where, due to uncomplicated access to the systemic circulation, this eicosanoid could contribute to renovascular tone regulation and, ultimately, arterial blood pressure control. Furthermore, since the proximal tubule is where most electrolyte and water reabsorption occurs (1), the capacity of 20-HETE to potently inhibit Na ϩ /K ϩ -ATPase activity in this region of the nephron probably contributes to its known natriuretic and diuretic effects (4,62,74). In rats, CYP4A expression and 20-HETE formation have also been noted in renal microvessels (19,29,75), another proposed site where this eicosanoid influences vascular tone, autoregulation of renal blood flow, and/or tubuloglomerular feedback (9,10).…”

Section: -Hete Formation By Human Renal P450 Enzymesmentioning

confidence: 99%

Formation of 20-Hydroxyeicosatetraenoic Acid, a Vasoactive and Natriuretic Eicosanoid, in Human Kidney

Lasker¹,

Chen²,

Wolf³

et al. 2000

Journal of Biological Chemistry

284

265

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20-Hydroxyeicosatetraenoic acid (20-HETE), an -hydroxylated arachidonic acid (AA) metabolite, elicits specific effects on kidney vascular and tubular function that, in turn, influence blood pressure control. The human kidney's capacity to convert AA to 20-HETE is unclear, however, as is the underlying P450 catalyst. Microsomes from human kidney cortex were found to convert AA to a single major product, namely 20-HETE, but failed to catalyze AA epoxygenation and midchain hydroxylation. Despite the monophasic nature of renal AA -hydroxylation kinetics, immunochemical studies revealed participation of two P450s, CYP4F2 and CYP4A11, since antibodies to these enzymes inhibited 20-HETE formation by 65.9 ؎ 17 and 32.5 ؎ 14%, respectively. Western blotting confirmed abundant expression of these CYP4 proteins in human kidney and revealed that other AA-oxidizing P450s, including CYP2C8, CYP2C9, and CYP2E1, were not expressed. Immunocytochemistry showed CYP4F2 and CYP4A11 expression in only the S2 and S3 segments of proximal tubules in cortex and outer medulla. Our results demonstrate that CYP4F2 and CYP4A11 underlie conversion of AA to 20-HETE, a natriuretic and vasoactive eicosanoid, in human kidney. Considering their proximal tubular localization, these P450 enzymes may partake in pivotal renal functions, including the regulation of salt and water balance, and arterial blood pressure itself.

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Section: -Hete Formation By Human Renal P450 Enzymesmentioning

confidence: 99%

Formation of 20-Hydroxyeicosatetraenoic Acid, a Vasoactive and Natriuretic Eicosanoid, in Human Kidney

Lasker¹,

Chen²,

Wolf³

et al. 2000

Journal of Biological Chemistry

284

265

View full text Add to dashboard Cite

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“…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).…”

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confidence: 99%

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confidence: 99%

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

Sarkis¹,

Ito²,

Mori³

et al. 2005

American Journal of Physiology-Renal Physiology

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. Cytochrome P-450-dependent metabolism of arachidonic acid in the kidney of rats with diabetes insipidus. Am J Physiol Renal Physiol 289: F1333-F1340, 2005. First published July 12, 2005 doi:10.1152/ajprenal.00188.2005.-This study compared the renal metabolism of arachidonic acid in Brattleboro (BB) (vasopressin deficient) and Long-Evans (LE) control rats and the effects of a cytochrome P-450 (CYP) inhibitor 1-aminobenzotriazole (ABT) on renal function in these animals. The production of 20-hydroxyeicosatetraenoic acid (20-HETE) by renal cortical and outer medullary microsomes was significantly greater in BB than in LE rats (155 Ϯ 16 vs. 92 Ϯ 13 and 59 Ϯ 7 vs. 33 Ϯ 3 pmol ⅐ min Ϫ1 ⅐ mg protein Ϫ1 ). Renal cortical epoxygenase activity was not different in these strains. The expression of CYP4A proteins was 58 and 78% higher in the renal cortex and outer medulla of BB than in LE rats. Chronic treatment of BB rats with a vasopressin type 2 receptor agonist for 1 wk normalized the renal production of 20-HETE. Chronic blockade of the formation of 20-HETE and EETs with ABT had little effect on renal function in LE rats. However, urine flow increased by 54% and urine osmolarity decreased by 33% in BB rats treated with ABT. Plasma levels of oxytocin fell significantly from 7.2 Ϯ 1.3 to 3.9 Ϯ 1.0 pg/ml. The effects of ABT in BB rats were attenuated by chronic infusion of oxytocin (0.7 ng ⅐ min Ϫ1 ⅐ 100 g Ϫ1 ) to maintain fixed high plasma levels of this hormone. These results indicate that the expression of CYP4A protein and the renal formation of 20-HETE are elevated in the kidney of BB rats due to a lack of vasopressin and that chronic blockade of the formation of 20-HETE and EETs with ABT promotes water excretion in vasopressin-deficient BB rats by reducing the circulating levels of oxytocin, which is a weak vasopressin agonist. Brattleboro rats; 20-hydroxyeicosatetraenoic acid; cytochrome P-450; epoxyeicosatrienoic acid; renal hemodynamics ARACHIDONIC ACID (AA) is metabolized by cytochrome P-450 (CYP) enzymes in the kidney to produce epoxyeicosatrienoic acids (EETs), 20-hydroxyeicosatetraenoic acid (20-HETE), and dihydroxyeicosatrienoic acids (DiHETEs). These compounds have been reported to play an important role in the control of both renal tubular and vascular function (26). EETs are potent endothelial-derived vasodilators in the renal circulation (17, 47). They also inhibit sodium and water reabsorption in the collecting duct (40). In contrast, 20-HETE is produced by vascular smooth muscle cells and is a potent constrictor of renal arterioles (5,19,23). 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 an...

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“…9 -11 Eicosanoids that inhibit tubular sodium transport are also produced by cytochrome P-450 (CYP 450) monooxygenase metabolism of arachidonic acid (AA); 20-HETE is the major metabolite of this pathway in mammalian kidney. This compound inhibits sodium transport at the proximal tubule Na ϩ -K ϩ -ATPase 12 and, most importantly, at the thick ascending limb NKCC. 13 The inhibitory action on the NKCC cotransporter is possibly mediated by impaired apical K ϩ -channel recycling of K ϩ .…”

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confidence: 99%

20-HETE and Furosemide-Induced Natriuresis in Salt-Sensitive Essential Hypertension

et al. 2003

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Abstract-Cyclooxygenase metabolites of arachidonic acid modulate the natriuretic effect of furosemide. It is not known whether 20-HETE, a monooxygenase metabolite of arachidonic acid that also inhibits sodium transport, participates in the action of furosemide. We measured urine sodium (UNaV) and 20-HETE during furosemide diuresis (40 mg three times over 12 hours) in 12 salt-sensitive (SS) and 11 salt-resistant (SR), salt-replete hypertensive subjects (126Ϯ24 mmol/24 hours positive sodium balance produced by 160-mmol-sodium diet and 2 L saline infusion). Individual systolic blood pressure decreases from the salt-replete to the salt-depleted state were the index of salt-sensitivity. SS had low plasma renin with blunted responses to changes in salt balance, inappropriate plasma aldosterone, and an increased aldosterone/renin ratio.

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20-Hydroxyeicosa-tetraenoic acid (20 HETE) activates protein kinase C. Role in regulation of rat renal Na+,K+-ATPase.

Abstract: It is well documented that the activity of Na

Cited by 148 publications

References 44 publications

Formation of 20-Hydroxyeicosatetraenoic Acid, a Vasoactive and Natriuretic Eicosanoid, in Human Kidney

Formation of 20-Hydroxyeicosatetraenoic Acid, a Vasoactive and Natriuretic Eicosanoid, in Human Kidney

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

20-HETE and Furosemide-Induced Natriuresis in Salt-Sensitive Essential Hypertension

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