Eicosanoids in renal function

Lote, Christopher J.; Haylor, J.

doi:10.1016/0952-3278(89)90134-8

Cited by 41 publications

(18 citation statements)

References 114 publications

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“…The reasons for the delay require some comment. It has been emphasized that exogenous PG, even when infused directly into the kidney, may not readily attain an effective concentration at all intrarenal sites of action (Ballermann, Levenson & Brenner, 1986;Lote & Haylor, 1989). PG action on collecting duct transport, responsible for diuresis and natriuresis, is not rapid in onset: about 15 min are required in vitro before maximal effect is seen (Stokes & Kokko, 1977).…”

Section: Discussionmentioning

confidence: 99%

Modulation of renal medullary ionic hypertonicity by prostaglandins: data from tissue admittance studies in the rat.

Dobrowolski

Kompanowska-Jezierska

Sadowski

1995

The Journal of Physiology

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1. Modulation of the cortico‐papillary electrolyte gradient by prostaglandins (PG) was studied in the kidney of anaesthetized rats. The intrarenal PG activity was varied by synthesis blockade with indomethacin (Ind) or meclophenamate (Me) and by intrarenal infusion of prostaglandin E2 (PGE2). 2. The interstitial electrolyte concentration in the medulla was continuously recorded in the kidney in situ as tissue electrical admittance (reciprocal impedance); the total renal blood flow (RBF), inulin clearance (Cin) and renal excretion were measured simultaneously. 3. Indomethacin and Me (15 mg kg‐1 h‐1) increased tissue admittance 15‐20% in the inner and 12‐15% in the outer medulla (P < 0.001) whereas PGE2 (300 ng kg‐1 min‐1) decreased admittance 14 and 8%, respectively (P < 0.01). 4. Renal blood flow and Cin were not affected by intrarenal PG activity changes. There was an increase in urine concentration after PG blockade and a delayed decrease after PGE2 infusion. 5. A joint analysis of the dynamics of medullary tissue admittance, renal haemodynamics and renal excretion provides evidence that PGs modify the medullary ionic hypertonicity by affecting NaCl transport in the ascending limb of the loop of Henle.

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Section: Discussionmentioning

confidence: 99%

Modulation of renal medullary ionic hypertonicity by prostaglandins: data from tissue admittance studies in the rat.

Dobrowolski

Kompanowska-Jezierska

Sadowski

1995

The Journal of Physiology

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“…After WD, the urinary PGE 2 excretion was increased in WT mice, but not in COX-2 Ϫ/Ϫ mice. Urinary PGE 2 excretion is mainly derived from medullary synthesis (34). It is concluded that the enhanced renal medullary PGE 2 synthesis after WD is mediated solely by COX-2.…”

mentioning

confidence: 91%

COX-2 disruption leads to increased central vasopressin stores and impaired urine concentrating ability in mice

Nørregaard

Madsen

Hansen

et al. 2011

American Journal of Physiology-Renal Physiology

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Nørregaard R, Madsen K, Hansen PB, Bie P, Thavalingam S, Frøkiaer J, Jensen BL. COX-2 disruption leads to increased central vasopressin stores and impaired urine concentrating ability in mice. Am J Physiol Renal Physiol 301: F1303-F1313, 2011. First published August 31, 2011 doi:10.1152/ajprenal.00665.2010.-It was hypothesized that cyclooxygenase-2 (COX-2) activity promotes urine concentrating ability through stimulation of vasopressin (AVP) release after water deprivation (WD). COX-2-deficient (COX-2 Ϫ/Ϫ , C57BL/6) and wild-type (WT) mice were water deprived for 24 h, and water balance, central AVP mRNA and peptide level, AVP plasma concentration, and AVP-regulated renal transport protein abundances were measured. In male COX-2 Ϫ/Ϫ , basal urine output and water intake were elevated while urine osmolality was decreased compared with WT. Water deprivation resulted in lower urine osmolality, higher plasma osmolality in COX-2 Ϫ/Ϫ mice irrespective of gender. Hypothalamic AVP mRNA level increased and was unchanged between COX-2 Ϫ/Ϫ and WT after WD. AVP peptide content was higher in COX-2 Ϫ/Ϫ compared with WT. At baseline, plasma AVP concentration was elevated in conscious chronically catheterized COX-2 Ϫ/Ϫ mice, but after WD plasma AVP was unchanged between COX-2 Ϫ/Ϫ and WT mice (43 Ϯ 11 vs. 70 Ϯ 16 pg/ml). Renal V2 receptor abundance was downregulated in COX-2 Ϫ/Ϫ mice. Medullary interstitial osmolality increased and did not differ between COX-2 Ϫ/Ϫ and WT after WD. Aquaporin-2 (AQP2; cortex-outer medulla), AQP3 (all regions), and UT-A1 (inner medulla) protein abundances were elevated in COX-2 Ϫ/Ϫ at baseline and further increased after WD. COX-2 Ϫ/Ϫ mice had elevated plasma urea and creatinine and accumulation of small subcapsular glomeruli. In conclusion, hypothalamic COX-2 activity is not necessary for enhanced AVP expression and secretion in response to water deprivation. Renal medullary COX-2 activity negatively regulates AQP2 and -3. The urine concentrating defect in COX-2 Ϫ/Ϫ is likely caused by developmental glomerular injury and not dysregulation of AVP or collecting duct aquaporins.aquaporins; PGE 2; water deprivation MICE DEFICIENT IN PGE 2 EP1 receptor signaling display a mild urine concentrating defect that is coupled to a lower vasopressin (AVP) mRNA level in the hypothalamus (30). However, the source of PGE 2 that potentially activates the EP1 receptor in the neurons of hypothalamic nuclei to promote AVP expression and secretion is not clear. Cyclooxygenase type 2 (COX-2) which is expressed in the hypothalamus (10), is a rapidly inducible enzyme isoform that is a likely candidate. Intracerebroventricular application of the nonselective COX inhibitor meclofenamate impairs hyperosmolality-induced AVP secretion (49). Hypothalamic supraoptic nucleus (SON) neurons are sensitive to experimental addition of prostanoids, particularly PGE 2 and PGF 2␣ (46), which promotes electric and secretory activity. It is not known whether hypothalamic COX-2 activity is regulated by physiological variations in plasma o...

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“…This occurs alongside increased urinary PGE2 and mRNA encoding cPGES, suggesting that PGE2 is necessary for fluid excretion, but the possibility that PGE2 levels may be flow-induced should also be considered. 79 AQP2 levels are increased in mPGES-1 KO mice at baseline, yet plasma VP levels are comparable between KO and WT mice 78 . Similar to the conclusion drawn from EP3 KO mice, this result suggests that under baseline conditions, PGE2 plays a role in decreasing AQP2 levels.…”

Section: A Role For Renal Prostanoids In Physiologic Water Excretionmentioning

confidence: 99%

“…18,49,82 This notion is supported by the fact that the COX-2 inhibitor, meloxicam, did not induce significant changes in functional urinary parameters, 81 but did severely downregulate AQP2, as did the nonselective COX inhibitors, indomethacin and ibuprofen. Because urinary PGE2 may be mostly derived from interstitial cell production, 79 the lack of decreased urinary PGE2 observed in COX-inhibitortreated rats 81 may reflect an inability of the drug to reach these cells in the papilla, where renal blood flow is relatively low. Furthermore, the three nonsteroidal antiinflammatory drugs used in the study can cross the blood-brain barrier 83,84 ; thus, whether their effects are restricted to the CD or due to effects on the hypothalamus is an issue for speculation.…”

Section: A Role For Renal Prostanoids In Physiologic Water Excretionmentioning

confidence: 99%

Is There a Role for PGE2 in Urinary Concentration?

Olesen

Fenton

2013

Journal of the American Society of Nephrology

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Prostanoids are prominent, yet complex, components in the maintenance of body water homeostasis. Recent functional and molecular studies have revealed that the local lipid mediator PGE2 is involved both in water excretion and absorption. The biologic actions of PGE2 are exerted through four different G-protein-coupled receptors; designated EP1-4, which couple to separate intracellular signaling pathways. Here, we discuss new developments in our understanding of the actions of PGE2 that have been uncovered utilizing receptor specific agonists and antagonists, EP receptor and PG synthase knockout mice, polyuric animal models, and the new understanding of the molecular regulation of collecting duct water permeability. The role of PGE2 in urinary concentration comprises a variety of mechanisms, which are not fully understood and likely depend on which receptor is activated under a particular physiologic condition. EP3 and microsomal PG synthase type 1 play a role in decreasing collecting duct water permeability and increasing water excretion, whereas EP2 and EP4 can bypass vasopressin signaling and increase water reabsorption through two different intracellular signaling pathways. PGE2 has an intricate role in urinary concentration, and we now suggest how targeting specific prostanoid receptor signaling pathways could be exploited for the treatment of disorders in water balance. The neurohypophyseal hormone, vasopressin (VP), is a major regulator of renal water excretion, predominantly through the seven trans-membrane receptor (7TMR) V2R. It binds to Gas, inducing the cAMP second messenger system, resulting in increased NaCl absorption by the thick ascending limb and increased urea transport in the inner medullary collecting ducts (IMCDs). [1][2][3] In addition, VP induces accumulation of the water channel aquaporin-2 (AQP2) in the rate-limiting apical plasma membrane of collecting duct (CD) principal cells, 4 a process that involves a diverse range of post-translational modifications including phosphorylation of AQP2. 5 Thus, VP increases the osmotic gradient for water transport and the water permeability (Pf) of the CD simultaneously.In addition to systemic hormones, local regulatory factors play a role in the CD, of which PGE2 (Figure 1) is the focus of this review. 6-9 PGE2 has a diverse range of biologic actions elicited by four different 7TMRs. The renal localization of EP receptors and intracellular signaling pathways are diverse (Table 1). Here, we propose that urinary concentration does not rely exclusively on fluctuations in plasma VP concentrations, but that the locally derived lipid mediator, PGE2, plays an important role in regulating water excretion. PGE2 IN THE MODULATION OF URINARY CONCENTRATING MECHANISMSThe ability of PGE2 to modulate the effects of VP in the CD has been described in a range of experimental studies and discussed in previous reviews. [36][37][38][39] The present focus is on understanding the mechanisms for this effect, and on recent in vivo studies elucidating the role of P...

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Eicosanoids in renal function

Cited by 41 publications

References 114 publications

Modulation of renal medullary ionic hypertonicity by prostaglandins: data from tissue admittance studies in the rat.

Modulation of renal medullary ionic hypertonicity by prostaglandins: data from tissue admittance studies in the rat.

COX-2 disruption leads to increased central vasopressin stores and impaired urine concentrating ability in mice

Is There a Role for PGE2 in Urinary Concentration?

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