H-K-ATPase in distal renal tubular acidosis: urinary tract obstruction, lithium, and amiloride

Eiam‐Ong, Somchai; Dafnis, Eugene; Spohn, Martha; Kurtzman, Neil A.; Sabatini, Sandra

doi:10.1152/ajprenal.1993.265.6.f875

Cited by 21 publications

(13 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the present study, we observed maintained targeting of ␣-, ␤-, and ␥-ENaC in BUO and of ␣-and ␤-ENaC in obstructed kidneys from UUO rats, which in part may be caused by increased aldosterone levels as has been demonstrated in previous studies in rats with urinary tract obstruction (6,31,37). This finding is consistent with previous observations on AQP2 in response to obstruction, where protein expression and labeling intensity was reduced after BUO but with maintained apical targeting of AQP2 (9).…”

Section: Discussionsupporting

confidence: 87%

Altered expression of epithelial sodium channel in rats with bilateral or unilateral ureteral obstruction

Li¹,

Wang²,

Nørregaard³

et al. 2007

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

.-The roles of epithelial sodium channel (ENaC) subunits (␣, ␤, and ␥) in the impaired renal reabsorption of sodium and water were examined in rat models with bilateral (BUO) or unilateral ureteral obstruction (UUO) for 24 h or with BUO followed by release of obstruction and 3 days of observation (BUO-3dR). In BUO rats, plasma osmolality was increased dramatically, whereas plasma sodium concentration was decreased. Immunoblotting revealed a significantly decreased expression of ␣-ENaC (57 Ϯ 7%), ␤-ENaC (19 Ϯ 5%), and ␥-ENaC (51 Ϯ 10%) as well as 11␤-hydroxysteroid dehydrogenase type 2 (11␤-HSD2) in the cortex and outer medulla (CϩOM) compared with sham-operated controls. This was confirmed by immunohistochemistry. BUO-3dR was associated with polyuria and impaired renal sodium handling. The protein abundance and the apical labeling of ␣-ENaC were significantly increased, whereas ␤-and ␥-ENaC as well as 11␤-HSD2 expression remained decreased. In UUO rats, expression of ␣-and ␤-ENaC and 11␤-HSD2 decreased in the CϩOM in the obstructed kidney. In contrast, the abundance and the apical labeling of ␣-ENaC in the nonobstructed kidneys were markedly increased, suggesting compensatory upregulation in this kidney. In conclusion, ␣-, ␤-, and ␥-ENaC expression levels are downregulated in the obstructed kidney. The expression and apical labeling of ␣-ENaC were increased in BUO-3dR rats and in the nonobstructed kidneys from UUO rats. These results suggest that altered expression of ␣-, ␤-, and ␥-ENaC may contribute to impaired renal sodium and water handling in response to ureteral obstruction.

show abstract

Section: Discussionsupporting

confidence: 87%

Altered expression of epithelial sodium channel in rats with bilateral or unilateral ureteral obstruction

Li¹,

Wang²,

Nørregaard³

et al. 2007

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…Of note, with reference to our findings, is the potential role played by the renin-angiotensin-aldosterone (RAA) system, which has a considerableinvolvement in the pathophysiology of UUO, as highlighted by the upregulation of plasma aldosterone levels secondary to 24 hours of UUO in rats [26]. Elsewhere, in pigs, it has been shown that there is an enhanced ipsilateral generation of intrarenal angiotensin II during UUO [27].…”

Section: Discussionmentioning

confidence: 72%

Analysis of Urinary and Plasma Electrolytes in a Rat Model of Unilateral Ureteric Obstruction (UUO)

Quinlan¹,

Pérez‐Barriocanal²,

Wright³

et al. 2008

TOUNJ

View full text Add to dashboard Cite

Abstract:Following unilateral ureteric obstruction (UUO), hydronephrosis is associated with long term reductions in renal blood flow (RBF) and glomerular filtration rate (GFR), tubular resistance to arginine-vasopressin (AVP), and reduced expression of aquaporin water channels and sodium (Na + ) and urea transporters. During UUO, renal function is contingent upon adaptive changes in the contralateral kidney. In the short term this response is associated with an increased GFR and a reduced expression of Na + transporters. We aimed to assess global renal function in UUO, including a comparison between the obstructed and non-obstructed kidneys.Adult male rats were subjected to UUO of either 3 or 10 days duration. Control rats underwent sham surgery. Before release of the ureteric ligature, blood and both bladder and obstructed renal pelvis urine was sampled, then both kidneys harvested. Urinary and plasma electrolytes and osmolality, and kidney weights, were measured.We observed i) mild uraemia in the obstructed animals, ii) extreme dilution of urine from the pelvis of the obstructed kidney in the absence of noteworthy alterations in plasma ions, and iii) evidence indicative of a contralateral diuresis/natriuresis.To the best of our knowledge, this is the first study simultaneously examining such an extensive range of urinary (bladder and obstructed renal pelvis) and plasma markers of renal function in UUO. The results demonstrate that UUO is associated with a small deterioration in overall renal function and marked changes in renal electrolyte handling, leading to changes in the composition of urinary output from both the non-obstructed and obstructed kidneys.

show abstract

“…39,[46][47][48] Also, the in vivo activity of ENaC, the lithium entry site of principal cells, has been reported to be functionally paired with CA activity, because CA inhibition by acetazolamide reduced the intracellular pH and ENaC activity in sweat duct cells and colon. 49,50 However, mpkCCD cells may not fully represent principal cells, and because intercalated cells express abundant levels of CA2, -4, 52,53 it has been suggested that acidosis-induced proliferation of a-intercalated cells may contribute to Li-NDI. 16 It is unlikely, however, that attenuation of Li-NDI in our mice is caused by direct action of acetazolamide on a-intercalated cells or collecting duct remodeling for several reasons.…”

Section: Discussionmentioning

confidence: 99%

Acetazolamide Attenuates Lithium–Induced Nephrogenic Diabetes Insipidus

Groot¹,

Sinke²,

Kortenoeven³

et al. 2015

JASN

View full text Add to dashboard Cite

To reduce lithium-induced nephrogenic diabetes insipidus (lithium-NDI), patients with bipolar disorder are treated with thiazide and amiloride, which are thought to induce antidiuresis by a compensatory increase in prourine uptake in proximal tubules. However, thiazides induced antidiuresis and alkalinized the urine in lithium-NDI mice lacking the sodium-chloride cotransporter, suggesting that inhibition of carbonic anhydrases (CAs) confers the beneficial thiazide effect. Therefore, we tested the effect of the CA-specific blocker acetazolamide in lithium-NDI. In collecting duct (mpkCCD) cells, acetazolamide reduced the cellular lithium content and attenuated lithium-induced downregulation of aquaporin-2 through a mechanism different from that of amiloride. Treatment of lithium-NDI mice with acetazolamide or thiazide/amiloride induced similar antidiuresis and increased urine osmolality and aquaporin-2 abundance. Thiazide/amiloride-treated mice showed hyponatremia, hyperkalemia, hypercalcemia, metabolic acidosis, and increased serum lithium concentrations, adverse effects previously observed in patients but not in acetazolamide-treated mice in this study. Furthermore, acetazolamide treatment reduced inulin clearance and cortical expression of sodium/hydrogen exchanger 3 and attenuated the increased expression of urinary PGE2 observed in lithium-NDI mice. These results show that the antidiuresis with acetazolamide was partially caused by a tubular-glomerular feedback response and reduced GFR. The tubular-glomerular feedback response and/or direct effect on collecting duct principal or intercalated cells may underlie the reduced urinary PGE2 levels with acetazolamide, thereby contributing to the attenuation of lithium-NDI. In conclusion, CA activity contributes to lithium-NDI development, and acetazolamide attenuates lithium-NDI development in mice similar to thiazide/amiloride but with fewer adverse effects.

show abstract

H-K-ATPase in distal renal tubular acidosis: urinary tract obstruction, lithium, and amiloride

Cited by 21 publications

References 0 publications

Altered expression of epithelial sodium channel in rats with bilateral or unilateral ureteral obstruction

Altered expression of epithelial sodium channel in rats with bilateral or unilateral ureteral obstruction

Analysis of Urinary and Plasma Electrolytes in a Rat Model of Unilateral Ureteric Obstruction (UUO)

Acetazolamide Attenuates Lithium–Induced Nephrogenic Diabetes Insipidus

Contact Info

Product

Resources

About