Sodium Reabsorption in the Thick Ascending Limb in Relation to Blood Pressure

Jung, Jeesun; Basile, David P.; Pratt, J. Howard

doi:10.1161/hypertensionaha.108.120246

Cited by 23 publications

(14 citation statements)

References 89 publications

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“…The reabsorption of NaCl is then completed as Na + exits the cell via the basolateral Na + -K + -ATPase while Cl − diffuses along its electrochemical gradient through basolateral KCl cotransporters or Cl − channels (Figure 1). Accordingly, the TAL is a nephron site where variations in Na + reaborption may influence long-term regulation of blood pressure and susceptibility to cardiovascular disease 6 . For instance, increased reabsorption in this nephron segment contributes to salt-sensitive hypertension 7 .…”

Section: I) Cox-2 Expression In the Thick Ascending Limb Of Henle’s Loopmentioning

confidence: 99%

Eicosanoids and tumor necrosis factor-alpha in the kidney

Ferreri¹,

Hao²,

Pedraza³

et al. 2012

Prostaglandins & Other Lipid Mediators

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The thick ascending limb of Henle’s loop (TAL) is capable of metabolizing arachidonic acid (AA) by cytochrome P450 (CYP450) and cyclooxygenase (COX) pathways and has been identified as a nephron segment that contributes to salt-sensitive hypertension. Previous studies demonstrated a prominent role for CYP450-dependent metabolism of AA to products that inhibited ion transport pathways in the TAL. However, COX-2 is constitutively expressed along all segments of the TAL and is increased in response to diverse stimuli. The ability of Tamm-Horsfall glycoprotein, a selective marker of cortical TAL (cTAL) and medullary (mTAL), to bind TNF and localize it to this nephron segment prompted studies to determine the capacity of mTAL cells to produce TNF and determine its effects on mTAL function. The colocalization of calcium-sensing receptor (CaR) and COX-2 in the TAL supports the notion that activation of CaR induces TNF-dependent COX-2 expression and PGE2 synthesis in mTAL cells. Additional studies showed that TNF produced by mTAL cells inhibits 86Rb uptake, an in vitro correlate of natriuresis, in an autocrine- and COX-2-dependent manner. The molecular mechanism for these effects likely includes inhibition of Na+-K+-2Cl− cotransporter (NKCC2) expression and trafficking.

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Section: I) Cox-2 Expression In the Thick Ascending Limb Of Henle’s Loopmentioning

confidence: 99%

Eicosanoids and tumor necrosis factor-alpha in the kidney

Ferreri¹,

Hao²,

Pedraza³

et al. 2012

Prostaglandins & Other Lipid Mediators

View full text Add to dashboard Cite

show abstract

“…Variations in NaCl reabsorption in this nephron segment, for example, may increase susceptibility to various cardiovascular diseases [13]. The TAL is capable of metabolizing arachidonic acid via the COX and cytochrome P450 pathways, and the products formed have been shown to inhibit ion transport in the TAL [14, 15].…”

Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor-alpha induces renal cyclooxygenase-2 expression in response to hypercalcemia

Battula

Hao

Pedraza

et al. 2012

Prostaglandins & Other Lipid Mediators

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The effect of tumor necrosis factor-alpha (TNF) on cyclooxygenase-2 (COX-2) expression in the renal outer medulla (OM) was determined in a model of dihydrotachysterol (DHT)-induced hypercalcemia. Increases in serum calcium and water intake were observed during ingestion of a DHT-containing diet in both wild type (WT) and TNF deficient mice (TNF−/−). Polyuria and a decrease in body weight were observed in response to DHT treatment in WT and TNF−/− mice. A transient elevation in urinary TNF was observed in WT mice treated with DHT. Moreover, increased urinary levels of prostaglandin E2 (PGE2) and a corresponding increase in COX-2 expression in the OM were observed in WT mice fed DHT. Increased COX-2 expression was not observed in TNF−/− mice fed DHT, and the characteristics of PGE2 synthesis were distinct from those in WT mice. This study demonstrates that COX-2 expression in the OM, secondary to hypercalemia, is TNF-dependent.

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“…This is best evidenced by the fact that pathologies that cause elevated TAL NaCl reabsorption increase blood pressure while those that reduce it cause hypotension (Hebert , Jung et al . ).…”

mentioning

confidence: 97%

TRPV4 mediates flow-induced increases in intracellular Ca in medullary thick ascending limbs

2015

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Medullary thick ascending limbs (mTAL) regulate Na balance and therefore blood pressure. We previously showed that cell swelling and luminal flow activates the mechano-sensitive channel TRPV4 in mTAL. Aim We hypothesized that TRPV4 mediates flow-induced increases in intracellular Ca (Cai) in rat mTALs. Methods We performed ratiometric measurements of Cai in perfused mTALs. Results Increasing luminal flow from 0 to 20 nL min-1 caused Cai to peak 231±29 nmol L-1 above basal concentrations (n=18). The general TRPV inhibitor ruthenium red at 15 and 50 umol L-1 reduced peak Cai by 41±9 (p<0.01;n=5) and 77±10 % (p<0.02;n=6). The selective TRPV4 inhibitor RN1734 at 10 and 50 umol L-1 reduced peak Cai by 46±11 (p<0.01;n=7) and 76±5% (p<0.02;n=5) respectively. To specifically target TRPV4, mTALs were transduced with adenoviruses expressing TRPV4 small hairpin (sh) RNA. In non-transduced control mTALs, luminal flow generated a peak increase in Cai of 111±21 nmol L-1 (n=8). In TRPV4shRNA-transduced mTALs, the Cai peak was reduced to 56±8 nmol L-1 (p<0.03,n=9). Removing extracellular Ca completely abolished flow-induced increases in Cai. Increasing luminal flow in the presence of hexokinase 20 (U/ml) to scavenge extracellular ATP did not modify significantly the increases in Cai induced by luminal flow. Finally, we studied the effect of the TRPV4 selective agonist GSK1016790A on Cai. In the absence of luminal flow, GSK1016790A (10 nmol L-1) increased Cai from 60±11 nmol L-1 to 262±71 nmol L-1 (p<0.05;n=7). Conclusion We conclude that flow-induced increases in Cai are mediated primarily by TRPV4 in the rat mTAL.

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Sodium Reabsorption in the Thick Ascending Limb in Relation to Blood Pressure

Cited by 23 publications

References 89 publications

Eicosanoids and tumor necrosis factor-alpha in the kidney

Eicosanoids and tumor necrosis factor-alpha in the kidney

Tumor necrosis factor-alpha induces renal cyclooxygenase-2 expression in response to hypercalcemia

TRPV4 mediates flow-induced increases in intracellular Ca in medullary thick ascending limbs

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