Physiologic and pathophysiologic roles of lipid mediators in the kidney

Hao, Chuan‐Ming; Breyer, Matthew D.

doi:10.1038/sj.ki.5002192

Cited by 151 publications

(127 citation statements)

References 204 publications

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“…[20][21][22] In parallel, we demonstrate that the renal content of 20-HETE exhibits a clear circadian pattern and that this pattern is significantly modified in kidneys of clock(2/2) mice. 20-HETE has a potent prohypertensive effect by acting as a vasoconstrictor of preglomerular arterioles, but it can also inhibit several important sodium transporters in the proximal tubule and the thick ascending limb (Na + -K + -adenosine triphosphatase, NHE3, NKCC2 Na 1 -K + -Cl 2 cotransporter 2), [23][24][25][26] thereby promoting sodium excretion and lowering BP.…”

Section: Discussionmentioning

confidence: 57%

The Circadian Clock Modulates Renal Sodium Handling

Nikolaeva

Pradervand

Centeno³

et al. 2012

Journal of the American Society of Nephrology

124

122

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The circadian clock contributes to the control of BP, but the underlying mechanisms remain unclear. We analyzed circadian rhythms in kidneys of wild-type mice and mice lacking the circadian transcriptional activator clock gene. Mice deficient in clock exhibited dramatic changes in the circadian rhythm of renal sodium excretion. In parallel, these mice lost the normal circadian rhythm of plasma aldosterone levels. Analysis of renal circadian transcriptomes demonstrated changes in multiple mechanisms involved in maintaining sodium balance. Pathway analysis revealed the strongest effect on the enzymatic system involved in the formation of 20-HETE, a powerful regulator of renal sodium excretion, renal vascular tone, and BP. This correlated with a significant decrease in the renal and urinary content of 20-HETE in clockdeficient mice. In summary, this study demonstrates that the circadian clock modulates renal function and identifies the 20-HETE synthesis pathway as one of its principal renal targets. It also suggests that the circadian clock affects BP, at least in part, by exerting dynamic control over renal sodium handling. Recent evidence indicates that the circadian clock is involved in BP control. In mice, suppression or decrease of the circadian clock activity via deletion of the circadian transcriptional activators Bmal1, Clock, or Npas2 leads to low BP, whereas its constitutive activation via deletion of the circadian repressors Cry1 and Cry2 results in salt-sensitive hypertension. 1-4 Wang et al. have recently shown that mice simultaneously devoid of three prolineand acidic amino acid-rich basic leucine zipper circadian transcriptional factors Dbp, Hlf, and Tef exhibit a significant reduction in BP. 5 Maintaining BP within the normal range strongly depends on the capacity of the kidney to precisely regulate sodium content in the extracellular space. Thus, dysregulation of molecular mechanisms involved in renal sodium handling could be partially responsible for the elevated or decreased BP observed in mice with genetically altered clocks. This hypothesis is supported by evidence in humans suggesting that alteration of circadian rhythms of urinary sodium excretion is the primary cause of disease in several forms of hyper-or hypotension. For instance, a decreased renal capacity to excrete sodium during the daytime correlates with nocturnal hypertension, whereas increased sodium excretion during the nighttime contributes to the maintenance of orthostatic hypotension. 6,7 Of note, important changes in the amplitude or the circadian phase of urinary excretion of sodium can be provoked not only by a pathologic process but also by a misalignment between the endogenous circadian clock and the imposed rest-activity or feeding cycles, or by sleep disturbance. For instance, Kamperis et al. have shown that acute sleep deprivation in humans leads to excessive natriuresis and kaliuresis during the subjective night and attenuation of the

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Section: Discussionmentioning

confidence: 57%

The Circadian Clock Modulates Renal Sodium Handling

Nikolaeva

Pradervand

Centeno³

et al. 2012

Journal of the American Society of Nephrology

124

122

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“…Hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) from the P450 monooxygenase pathway can constrict renal vessels and glomerular mesangial cells and have been implicated in the tubuloglomerular feedback and renal blood flow autoregulation of the kidney (95,96). Further details on the complex renal pathophysiology of eicosanoids can be found in a recent dedicated review (83).…”

Section: Microvascular Dysfunction and The Balance Between Vasoconstrmentioning

confidence: 99%

“…Eicosanoids are another class of mediators that exert complex effects on microcirculatory function after I/R. They are produced from arachidonic acid through three major enzymatic pathways: cyclooxygenase (COX), lipoxygenase (LO), and cytochrome P450 monooxygenase (83). It has long been recognized that prostanoids (made by COX-1 and -2) play a critical role in modulating renal blood flow and glomerular hemodynamics (84,85).…”

Section: Microvascular Dysfunction and The Balance Between Vasoconstrmentioning

confidence: 99%

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

Legrand

Mik

Johannes³

et al. 2008

Mol Med

237

169

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Ischemia is the most common cause of acute renal failure. Ischemic-induced renal tissue hypoxia is thought to be a major component in the development of acute renal failure in promoting the initial tubular damage. Renal oxygenation originates from a balance between oxygen supply and consumption. Recent investigations have provided new insights into alterations in oxygenation pathways in the ischemic kidney. These findings have identified a central role of microvascular dysfunction related to an imbalance between vasoconstrictors and vasodilators, endothelial damage and endothelium-leukocyte interactions, leading to decreased renal oxygen supply. Reduced microcirculatory oxygen supply may be associated with altered cellular oxygen consumption (dysoxia), because of mitochondrial dysfunction and activity of alternative oxygen-consuming pathways. Alterations in oxygen utilization and/or supply might therefore contribute to the occurrence of organ dysfunction. This view places oxygen pathways' alterations as a potential central player in the pathogenesis of acute kidney injury. Both in regulation of oxygen supply and consumption, nitric oxide seems to play a pivotal role. Furthermore, recent studies suggest that, following acute ischemic renal injury, persistent tissue hypoxia contributes to the development of chronic renal dysfunction. Adaptative mechanisms to renal hypoxia may be ineffective in more severe cases and lead to the development of chronic renal failure following ischemia-reperfusion. This paper is aimed at reviewing the current insights into oxygen transport pathways, from oxygen supply to oxygen consumption in the kidney and from the adaptation mechanisms to renal hypoxia. Their role in the development of ischemia-induced renal damage and ischemic acute renal failure are discussed.

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“…Multiple mechanisms including increased sorbitol pathway activity (1,2), non-enzymatic glycation and glycoxidation (3,4), enhanced oxidative-nitrosative stress (5,6), protein kinase C (7,8), poly(ADP-ribose) polymerase (9,10) and lipoxygenase (11,12) activation, and others have been implicated in the pathogenesis of chronic diabetic complications. The relations between individual mechanisms are not completely understood and require specific studies.…”

Section: Introductionmentioning

confidence: 99%

Aldose reductase inhibitor fidarestat counteracts diabetes-associated cataract formation, retinal oxidative-nitrosative stress, glial activation, and apoptosis

Drel

Pacher²,

Ali³

et al. 2008

Int J Mol Med

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Abstract. This study was aimed at evaluating the potent and specific aldose reductase inhibitor fidarestat, on diabetesassociated cataract formation, and retinal oxidative-nitrosative stress, glial activation, and apoptosis. Control and streptozotocin-diabetic rats were treated with or without fidarestat (16 mg kg -1 d -1 ) for 10 weeks after an initial 2-week period without treatment. Lens changes were evaluated by indirect ophthalmoscopy and portable slit lamp. Nitrotyrosine, poly(ADP-ribose), and glial fibrillary acidic protein expression were assessed by immunohistochemistry. The rate of apoptosis was quantified in flat-mounted retinas by TUNEL assay with immunoperoxidase staining. To dissect the effects of high glucose exposure in retinal microvascular cells, primary bovine retinal pericytes and endothelial cells were cultured in 5 or 30 mM glucose, with or without fidarestat (10 μM) for 3-14 days. Apoptosis was assessed by TUNEL assay, nitrotyrosine and poly(ADP-ribose) by immunocytochemistry, and Bax and Bcl-2 expression by Western blot analyses. Fidarestat treatment prevented diabetic cataract formation and counteracted retinal nitrosative stress, and poly(ADP-ribose) polymerase activation, as well as glial activation. The number of TUNEL-positive nuclei (mean ± SEM) was increased approximately 4-fold in diabetic rats vs. controls (207±33 vs. 49±4, p<0.01), and this increase was partially prevented by fidarestat (106±34, p<0.05 vs. untreated diabetic group). The apoptotic cell number increased with the prolongation of exposure of both pericytes and endothelial cells to high glucose levels. Fidarestat counteracted nitrotyrosine and poly(ADP-ribose) accumulation and apoptosis in both cell types. Antiapoptotic effect of fidarestat in high glucose-exposed retinal pericytes was not associated with the inhibition of Bax or increase in Bcl-2 expression. In conclusion, the findings, i) support an important role for aldose reductase in diabetes-associated cataract formation, and retinal oxidative-nitrosative stress, glial activation, and apoptosis, and ii) provide a rationale for the development of aldose reductase inhibitors, and, in particular, fidarestat, for the prevention and treatment of diabetic ocular complications.

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Physiologic and pathophysiologic roles of lipid mediators in the kidney

Cited by 151 publications

References 204 publications

The Circadian Clock Modulates Renal Sodium Handling

The Circadian Clock Modulates Renal Sodium Handling

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

Aldose reductase inhibitor fidarestat counteracts diabetes-associated cataract formation, retinal oxidative-nitrosative stress, glial activation, and apoptosis

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