COX-2 inhibition prevents downregulation of key renal water and sodium transport proteins in response to bilateral ureteral obstruction

Nørregaard, Rikke; Jensen, Boye L.; Li, Chunling; Wang, Weidong; Knepper, Mark A.; Nielsen, Søren; Frøkiær, Jørgen

doi:10.1152/ajprenal.00061.2005

Cited by 96 publications

(127 citation statements)

References 52 publications

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“…Immunohistochemistry confirmed an up-regulation of COX-2 in the obstructed kidneys. This is consistent with previous reports demonstrating an increase COX-2 expression in response to BUO, 12 in response to occlusion of a solitary kidney, 11 and also in kidney inner medullary (IM) of rats subjected to UUO. 10 Neonatally-induced ureteral obstruction results in severe injury of the obstructed kidney.…”

Section: Discussionsupporting

confidence: 93%

“…11 Moreover, it was recently demonstrated that acute BUO leads to marked upregulation of COX-2 in inner medulla; selective COX-2 inhibition prevents dysregulation of AQP2 in response to BUO, indicating that COX-2 may be an important factor contributing to the impaired renal water and sodium handling in response to BUO. 12 Thus, it is speculated that impaired renal water handling in response to neonatally-induced PUUO may be associated with altered expression of COX-2. In the present study, we examine whether long-term PUUO induced at birth affects the abundance of renal cyclooxygenase.…”

Section: Introductionmentioning

confidence: 99%

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Alteration of renal cyclooxygenase expression due to partial unilateral ureteral obstruction in neonatal

Li¹,

Zhang²,

Li³

et al. 2012

CUAJ

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E150Cite as: Can Urol Assoc J 2013;7:E150-E155. http://dx.doi.org/10.5489/cuaj.11163. Epub 2012 March 2. AbstractIntroduction: Impaired renal water handling in response to neonatally-induced partial unilateral ureteral obstruction (PUUO) may be associated with altered expression of cyclooxygenase (COX). The purpose of the present study was to examine whether long-term PUUO induced at birth was associated with changes of COX-2. Methods: Rats were subjected to PUUO (n = 14) or a sham operation (n = 12) within the first 48 hours of life. The rats were divided into 4 groups: (1) PUUO at 9 weeks (n = 7); (2) the sham operation at 9 weeks (n = 6); (3) PUUO at 15 weeks (n = 7); and (4) the sham operation at 15 weeks (n = 6). Urine and blood samples were collected before sacrificing the animals. Plasma potassium, creatinine and urea, as well as the osmolality and sodium of plasma and urine were tested in each sample. The expression of renal COX-1 and COX-2 was examined at 9 and 15 weeks in rats with neonatallyinduced PUUO within the first 48 hours of life by immunoblotting and immunocytochemistry. Results: PUUO caused a marked decrease in urine osmolality and a significant increase in urinary sodium of the obstructed kidney compared with the sham-operated kidney at 9 and 15 weeks. Immunoblotting analysis showed that an abundance of COX-2 in the obstructed kidney significantly increased compared with the non-obstructed kidney and sham-operated kidney at 9 weeks (p < 0.05) and 15 weeks (p < 0.05) in rats with PUUO. In contrast, COX-1 abundance in the obstructed kidney was similar to that in the non-obstructed kidney. Immunocytochemistry confirmed these findings. Conclusion: Renal COX-2 expression in the obstructed kidney is significantly altered in response to neonatally-induced PUUO. A marked increase in COX-2 indicates that it may be an important factor in reducing renal handling of sodium and water in response to PUUO. IntroductionCongenital obstructive nephropathy is the primary cause of renal insufficiency in children.1 Congenital ureteral obstruction is distinguished by the profound impairment of kidney functions.2 Previous studies have shown that unilateral ureteral complete obstruction in adult rats caused impairment of urinary concentrating ability.3,4 However, neonatal partial unilateral ureteral obstruction (PUUO) as an experimental model for congenital obstructive nephropathy is clinically much more common than complete obstruction. Wen and colleagues demonstrated that PUUO induced neonatally in rats was associated with the development of progressive hydronephrosis. 5 The rat was chosen because obstruction induced shortly after birth simulates obstruction in the last trimester in humans. In the pediatric population, obstruction at the pelvic-ureteral junction is mostly partial and congenital. Furthermore, with rats, we can obtain a sufficient number of obstructed animals to cover the large variety of responses to obstruction seen in clinical and experimental materials with respect to severity and changes in re...

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Alteration of renal cyclooxygenase expression due to partial unilateral ureteral obstruction in neonatal

Li¹,

Zhang²,

Li³

et al. 2012

CUAJ

View full text Add to dashboard Cite

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“…The COX-2 upregulation in the kidney is presumably regulated by inhibition of glyet al, 2004, 2005) or possibly other kinases (Li and Matsumura, 2008;Dong and Matsumura, 2008). The elevation of PGE 2 will suppress the expression of AQP2 (Norregaard et al, 2005) membrane of the collecting duct epithelium (Nejsum et al, 2005), which subsequently suppresses the water permeability and leads to polyuria (Rao et al, 2005;Kim et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Severe toxicity and cyclooxygenase (COX)-2 mRNA increase by lithium in the neonatal mouse kidney

et al. 2009

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-Functions of the kidney of mammals are immature during the neonatal period, and the neonatal kidney could be susceptible to chemicals, including drugs and environmental toxicants. Among these chemicals, cyclooxygenase (COX)-inducing chemicals should be given attentions as the potential kidney toxicants during the period, and we hypothesized that lithium chloride (LiCl) has such toxicity. Neonatal mice of C57BL/J strain were intraperitoneally injected with LiCl (2 mmol/kg body weight) daily until 21 days of age, and examined on 7 days and 21 days of age. Neonatal treatment of LiCl caused a -LiCl-treated neonates died during the second week of age. Histological examination revealed renal cysts on day 7 and hydronephrosis on day 21. in the surviving neonates. The present results showed that the kidney of mouse neonates is vulnerable to lithium, and suggested the possibility that COX-2 upregulation is responsible for the severe renal toxicity including hydronephrosis.

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“…During this period, intraurethral pressure is above normal range and intrarenal blood-flow is redistributed from medullar to cortex (13). These events under BUO conditions can increase renal vascular resistance and then, reduce GFR (14,15).…”

Section: Discussionmentioning

confidence: 99%

“…In OU, the initial event is vasodilatation, which lasts 90 minutes; then, more prominent drops occur in renal blood flow, that maybe attributed to release of strong vasoconstrictors, angiotensin II, and thromboxane A2 (7,11,13). During this period, intraurethral pressure is above normal range and intrarenal blood-flow is redistributed from medullar to cortex (13).…”

Section: Discussionmentioning

confidence: 99%

Sildenafil Citrate Can Reduce Pathological Post-obstructive Diuresis in a Rat Model ofBilateral Ureteral Obstruction

Mombeini¹,

Dadfar²,

Khazaeli³

et al. 2017

Jentashapir J Helath Res

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Purpose: The current study aimed at assessing the effect of oral sildenafil citrate on postobstructive diuresis and urinary electrolyte changes after the management of bilateral ureteral obstruction (BUO). Methods: Twenty-eight adult Munich-Wistar male rats were subjected to the surgery-induced BUO for 24 hours. In intervention group (n = 14) sildenafil citrate 200 mg/kg food was administered from the operation day for 72 hours, while in control group (n = 14) no drug was used. Daily urinary volume, urine sodium (mEq/day), potassium (mEq/day), and osmolality (mOsm/kg H2O) were measured on the day before BUO and for 2 days after BUO release. Results: In comparison to the control group, postobstructive diuresis was significantly lower in the sildenafil group (P value < 0.001), while urinary sodium and osmolality were both preserved better in this group (P value < 0.001); however, there were no significant difference in potassium level between the groups (P value = 0.285). Conclusions: Oral sildenafil citrate significantly decreased postobstructive diuresis and preserved urine sodium and osmolality near normal. These 2 effects mean a better preservation of renal function, while preventing massive postobstructive diuresis.

show abstract

COX-2 inhibition prevents downregulation of key renal water and sodium transport proteins in response to bilateral ureteral obstruction

Cited by 96 publications

References 52 publications

Alteration of renal cyclooxygenase expression due to partial unilateral ureteral obstruction in neonatal

Alteration of renal cyclooxygenase expression due to partial unilateral ureteral obstruction in neonatal

Severe toxicity and cyclooxygenase (COX)-2 mRNA increase by lithium in the neonatal mouse kidney

Sildenafil Citrate Can Reduce Pathological Post-obstructive Diuresis in a Rat Model ofBilateral Ureteral Obstruction

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