Transport defects of rabbit medullary thick ascending limb cells in obstructive nephropathy.

Hwang, Shiuh-Lin; Haas, Mark; Harris, H. W.; Silva, P.; Yalla, Subbarao V.; Sullivan, Megan R.; Otuechere, G.; Kashgarian, Michael; Zeidel, Mark L.

doi:10.1172/jci116173

Cited by 35 publications

(30 citation statements)

References 34 publications

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“…We consider such a mechanism, however, as less likely, because one would expect that the recirculating transepithelial salt transport rate in hydronephrotic kidneys should be lower than the tubular salt transport in intact, filtering kidneys. In fact, it has already been shown that ureteral occlusion leads to a rapid decline of salt transport by the TALH (18), which is compatible with the reduced expression of NKCC2 in our study. A reduction of tubular salt transport should increase basal COX-2 expression and at the same time attenuate the stimulation of COX-2 expression by maneuvers inhibiting tubular salt transport.…”

Section: Discussionsupporting

confidence: 92%

Upregulation of macula densa cyclooxygenase-2 expression is not dependent on glomerular filtration

Schweda

Kammerl

Wagner

et al. 2004

American Journal of Physiology-Renal Physiology

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. Upregulation of macula densa cyclooxygenase-2 expression is not dependent on glomerular filtration. Am J Physiol Renal Physiol 287: F95-F101, 2004. 10.1152/ ajprenal.00404.2003.-Although the regulation of cyclooxygenase-2 (COX-2) expression in the kidney cortex has been extensively characterized, the physiological control mechanisms of COX-2 expression at the level of the kidney and at the level of the tubular cells are not well understood. Based on the current hypothesis that tubular salt transport might be a crucial regulator of COX-2 expression, this study aimed to determine the impact of salt delivery to the tubules (glomerular filtration) for the regulation of COX-2 in the kidney cortex in vivo. To this end, glomerular filtration of the right kidney was abrogated by the ligation of the right ureter of male Sprague-Dawley rats. After 1 wk of ligation, the animals were treated with subcutaneous infusions of furosemide (12 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) or with a low-salt or a high-salt diet (0.02% wt/wt; 8% wt/wt), and COX-2 as well as renin mRNA expression were determined in the ligated and the nonligated contralateral kidney. During ureteral ligation, hydronephrosis developed with a reduction of medullary mass, while the cortex was preserved. Expressions of the Na-K-2Cl cotransporter isoforms A and B were both reduced in the hydronephrotic cortex to 70 and 35% of the corresponding contralateral intact kidney. Despite the abrogation of glomerular filtration, detected by inulin clearance measurements, renocortical COX-2 mRNA abundance was stimulated by furosemide treatment (3.2-fold) or low-salt diet (2.9-fold) to similar degrees compared with the intact contralateral kidney (2.7-fold for both treatments), whereas a high-salt diet did not significantly suppress COX-2 mRNA in the macula densa region of either kidney. Renin mRNA expression was regulated strictly in parallel in both kidneys, a low-salt diet or furosemide treatment stimulating and a high-salt diet suppressing it. We conclude from these findings that salt delivery to the tubules is not an essential requirement for the upregulation of COX-2 by salt deficiency or by loop diuretics in the rat kidney cortex nor is it for chronic stimulation of renin mRNA expression. kidney; renin; ureteral ligation IT IS WELL ESTABLISHED that the expressions of cyclooxygenase-2 (COX-2) in the cortical thick ascending limb of Henle (TALH) including the macula densa and of renin in the neighboring juxtaglomerular cells are regulated in parallel by a variety of physiologically relevant parameters such as sodium intake (13, 21, 36), renal perfusion pressure (15,22,31), or circulating levels of ANG II (4, 33). It has been speculated that the expression of COX-2 in the macula densa triggers the expression and the secretion of renin by the formation of prostanoids (12,14,28), which are direct stimulators of the renin system at the level of juxtaglomerular cells (20). The functional and molecular pathways controlling COX-2 expression in the TALH and in the macula densa cells at the...

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Section: Discussionsupporting

confidence: 92%

Upregulation of macula densa cyclooxygenase-2 expression is not dependent on glomerular filtration

Schweda

Kammerl

Wagner

et al. 2004

American Journal of Physiology-Renal Physiology

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“…Loop diuretics combined with oral salt supplementation are also an effective chronic therapy for the syndrome of inappropriate antidiuretic hormone (106), blunting the countercurrent mechanism, increasing water excretion, and correcting the associated hyponatremia. An acquired dysfunction of NKCC2 after ureteral obstruction can in turn lead to the salt wasting and impaired urinary concentrating ability that is characteristic of postobstructive renal function (107).…”

Section: Pathophysiology Of the Talmentioning

confidence: 99%

Thick Ascending Limb of the Loop of Henle

Mount

2014

Clinical Journal of the American Society of Nephrology

146

106

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The thick ascending limb occupies a central anatomic and functional position in human renal physiology, with critical roles in the defense of the extracellular fluid volume, the urinary concentrating mechanism, calcium and magnesium homeostasis, bicarbonate and ammonium homeostasis, and urinary protein composition. The last decade has witnessed tremendous progress in the understanding of the molecular physiology and pathophysiology of this nephron segment. These advances are the subject of this review, with emphasis on particularly recent developments.

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“…5). On the other hand, the relative conductances of Cl-and K+ were, respectively, decreased and increased in the CCD from UUO animals (14) ( ) (9) (8) (+ CONTROL (16) (-) (9) *tt .…”

Section: Discussionmentioning

confidence: 94%

“…However, the mechanisms underlying these disorders have not been fully evaluated. Only a few studies have assessed them at a segmental level (10)(11)(12)(13)(14)(15). The in vitro microperfusion studies of the rabbit CCD have demonstrated that unilateral ureteral obstruction (UUO) led to decreases in the lumen-negative transepithelial voltage (10,11) as well as in Na'-K+-ATPase activity (12) and in Na'-K' pump in situ turnover (13) in the CCD from obstructed rat kidneys after UUO.…”

mentioning

confidence: 99%

Electrical properties of the rabbit cortical collecting duct from obstructed kidneys after unilateral ureteral obstruction. Effects of renal decapsulation.

Muto¹,

Asano²

1994

J. Clin. Invest.

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Ureteral obstruction causes impaired salt wastage and K+ secretion in the distal nephron segments, including the cortical collecting duct (CCD). Recently, we demonstrated that conductances of Na+ and K+ in the apical membrane, as well as the electrogenic Na+-K+ pump activity and the relative K+ conductance in the basolateral membrane of the collecting duct cell, were inhibited in the obstructed kidney after unilateral ureteral obstruction (UUO). To examine whether the increased intrarenal pressure might be causally related to these abnormalities in the CCD, the effects of unilateral renal decapsulation, a maneuver that partially blocks the increase in renal pressure, were evaluated with microelectrode techniques in isolated CCDs from UUO and sham-operated (control) rabbits 24 h after operation. Renal decapsulation had no effects on barrier voltages and conductances in the CCD from control animals. The lumen-negative transepithelial (VT) and basolateral membrane (VB) voltages as well as the transepithelial (GT) and the apical membrane (GA) conductances were decreased in the CCD from UUO animals compared with control animals. Pretreatment of renal decapsulation partially corrected the decreases in VT, VB, GT, and GA seen in the CCD from UUO animals. The changes in apical membrane voltage and GT upon addition of luminal amiloride and Ba2+, and the changes in VB upon addition of bath ouabain, were also decreased in the CCD from UUO animals compared with control animals. Pretreatment of renal decapsulation also partially corrected the above abnormalities seen in UUO animals, whereas it had no effect in control animals. The transference numbers for Cl-(tc) and K+ (tK) in the basolateral membrane were, respectively, increased and decreased in the CCD from UUO animals compared with control animals. Pretreatment of renal decapsulation also partially corrected the changes in tc, and tK seen in UUO animals, whereas it had no effect in control animals. We conclude that, in UUO animals, renal decapsulation partially corrects the inhibition of apical Na+ and K+ conductances as well as basolateral Na+-K+ pump activity and relative K+ conductance seen after UUO, whereas in control animals it has no

show abstract

Transport defects of rabbit medullary thick ascending limb cells in obstructive nephropathy.

Cited by 35 publications

References 34 publications

Upregulation of macula densa cyclooxygenase-2 expression is not dependent on glomerular filtration

Upregulation of macula densa cyclooxygenase-2 expression is not dependent on glomerular filtration

Thick Ascending Limb of the Loop of Henle

Electrical properties of the rabbit cortical collecting duct from obstructed kidneys after unilateral ureteral obstruction. Effects of renal decapsulation.

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