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Jens Christian Djurhuus

Publications and source records attributed to Jens Christian Djurhuus.

At least 19 recordsLinked to original sources
PubMed2006

Glomerular and tubular function during AT1 receptor blockade in pigs with neonatal induced partial ureteropelvic obstruction.

Previously, we showed that neonatal induced chronic partial unilateral ureteral obstruction (PUUO) of the multipapillary pig kidney decreased glomerular filtration rate (GFR) of the obstructed kidney. We hypothesized that ANG II and nitric oxide (NO) are important for the changes in renal function and in the present study we examined the effects of chronic AT1 receptor blockade using CV-11974 (0.12 mg/h candesartan from age 23 to 30 days) on kidney function development after PUUO was induced in 2-day-old piglets. Moreover, the effect of superimposed acute NO inhibition using N(G)-nitro-l-arginine methyl ester (l-NAME; 15 mg/kg) was examined to identify if this has diagnostic potential. PUUO significantly increased GFR in the nonobstructed contralateral kidney independent of candesartan. In candesartan-treated piglets, the l-NAME-induced GFR reduction seen in normal and nonobstructed kidneys was absent in the partial obstructed kidneys. Urine output and fractional excretion of water were increased from the partial obstructed kidneys. Consistent with this immunohistochemical analyses showed a reduced aquaporin-2 labeling in the collecting duct principal cells. Moreover, renal sodium handling was compromised by PUUO evidenced by an increased fractional excretion of sodium which was enhanced by candesartan treatment. In conclusion, our findings suggest that the counterbalance between AT1 receptor-mediated vasoconstriction and NO-mediated vasodilatation which maintain GFR in normal young porcine kidneys is changed by neonatal induced chronic PUUO. This may have diagnostic potential in children with suspected congenital obstruction. Our results also demonstrate compromised tubular functions in response to chronic PUUO despite preservation of glomerular function.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Candesartan prevents long-term impairment of renal function in response to neonatal partial unilateral ureteral obstruction.

Angiotensin II (ANG II) plays an important role in the development of obstructive nephropathy. Here, we examined the effects of the ANG II receptor type 1 (AT1R) blockade using candesartan on long-term renal molecular and functional changes in response to partial unilateral ureteral obstruction (PUUO). Newborn rats were subjected to severe PUUO or sham operation (Sham) within the first 48 h of life. Candesartan was provided in the drinking water (10 mg.kg(-1).day(-1)) from day 21 of life until 10 wk of age. Renal blood flow (RBF) was evaluated by MRI, glomerular filtration rate (GFR) was measured using the renal clearance of (51)Cr-EDTA, and the renal expression of Na-K-ATPase and the collecting duct water channel aquaporin-2 (AQP2) was examined by immunoblotting and immunocytochemistry. At 10 wk of age, PUUO significantly reduced RBF (0.8 +/- 0.1 vs. 1.6 +/- 0.1 ml.min(-1).100 g body wt(-1); P < 0.05) and GFR (37 +/- 16 vs. 448 +/- 111 microl.min(-1).100 g body wt(-1); P < 0.05) compared with Sham. Candesartan prevented the RBF reduction (PUUO+CAN: 1.6 +/- 0.2 vs. PUUO: 0.8 +/- 0.1 ml.min(-1).100 g body wt(-1); P < 0.05) and attenuated the GFR reduction (PUUO+CAN: 265 +/- 68 vs. PUUO: 37 +/- 16 microl.min(-1).100 g body wt(-1); P < 0.05). PUUO was also associated with a significant downregulation in the expression of Na-K-ATPase (75 +/- 12 vs. 100 +/- 5%, P < 0.05) and AQP2 (52 +/- 15 vs. 100 +/- 4%, P < 0.05), which were also prevented by candesartan (Na-K-ATPase: 103 +/- 8 vs. 100 +/- 5% and AQP2: 74 +/- 13 vs. 100 +/- 4%). These findings were confirmed by immunocytochemistry. Consistent with this, candesartan treatment partly prevented the reduction in solute free water reabsorption and attenuated fractional sodium excretion in rats with PUUO. In conclusion, candesartan prevents or attenuates the reduction in RBF, GFR and dysregulation of AQP2 and Na-K-ATPase in response to congenital PUUO in rats, suggesting that AT1R blockade may protect the neonatally obstructed kidney against development of obstructive nephropathy.

Aldosterone↗
PubMed2006

Increased TGF-alpha and EGF Receptor mRNA expression in response to neonatal unilateral partial ureter obstruction in rats.

AIM: To evaluate the potential role of members of the epidermal growth factor (EGF) family in altered renal growth caused by partial ureteral obstruction in the developing obstructed and non-obstructed kidneys. METHODS: During anesthesia either the upper fourth (n = 6-7) or the upper two-thirds of the left ureter (n = 6-7) were embedded into the psoas muscle in newborn rats resulting in mild or severe partial unilateral obstruction, respectively, which was maintained during the following 24 weeks. Sham-operated control rats were prepared in parallel (n = 6-7). Real time PCR assays were used to quantify mRNA encoding EGF, TGF-alpha, HB-EGF and EGF receptor. The expression of ribosomal RNA was determined to relate the specific mRNA expression of members of the EGF system. RESULTS: Relative expression of TGF-alpha and EGF receptor mRNA levels were elevated significantly both in the severe and mild obstructed kidney compared with the contralateral or sham-operated kidneys after 24 weeks of obstruction. However, the expression of neither EGF nor HB-EGF was changed after obstruction. CONCLUSION: The increased expression of TGF-alpha and its receptor in the obstructed kidney might be related to a cell-survival function in the affected cells possibly by protecting them from entering apoptosis.

Animals↗
PubMed2006

Nocturia and circadian blood pressure profile in healthy elderly male volunteers.

PURPOSE: Nocturia is attributed to nocturnal polyuria and/or decreased functional bladder capacity. In this study we elucidated the mechanisms behind circadian fluid regulation and the occurrence of nocturia in healthy elderly males, specifically to determine the role of urine output and regulating hormones, blood pressure, and average voided volumes. MATERIALS AND METHODS: A total of 18 males 55 to 73 years old (mean age 61.1) were included in the study. Voiding habits were assessed by completion of a 7-day frequency volume chart recording all fluid intake and voiding. The subjects subsequently underwent inpatient circadian studies measuring the diurnal rhythm of blood pressure, vasopressin, atrial natriuretic peptide, angiotensin II, aldosterone and urine volume. RESULTS: Of the nightly home recordings 25% showed nocturia, characterized by a higher 24-hour and nighttime urine volume. During the inpatient studies 12 of the 18 participants experienced a nocturnal void. Nocturia nights were characterized by significantly decreased day-to-night ratios in urine output and a higher nighttime mean arterial blood pressure. A circadian variation in plasma arginine vasopressin was seen only in the group without nocturia. The other hormones revealed a circadian rhythm similar in the 2 groups. CONCLUSIONS: In healthy males with occasional nocturia, the occurrence of nocturia seems to be associated with a blunting of the circadian rhythm of diuresis and increased arterial blood pressures during the night. These findings may implicate a role for a baroregulatory related mechanism in nocturia.

Aged↗
PubMed2006

Bladder reservoir function in children with monosymptomatic nocturnal enuresis and healthy controls.

PURPOSE: We investigated bladder reservoir function in children with monosymptomatic nocturnal enuresis and in healthy controls. MATERIALS AND METHODS: A total of 18 children with monosymptomatic nocturnal enuresis and 119 controls who were 7 to 13 years old were recruited. Children completed frequency volume charts and measurements of nocturnal urine production. Mean diuresis in the period preceding each voiding was calculated. Those with enuresis were grouped according to bladder capacity and hospitalized for 4 nights, including a baseline night and 3 with an oral water load. Enuresis volumes and post-void residual volume were estimated, allowing the calculation of bladder volume at the time of enuresis. RESULTS: Nine children with monosymptomatic nocturnal enuresis were characterized as having normal bladder capacity and 9 had decreased bladder capacity. We found large intra-individual variability in daytime voided volume in all 3 groups of participants. Children with enuresis and small bladder capacity generally voided with volumes close to maximal voided volume. A total of 93 enuresis episodes were recorded. Large intra-individual variability was seen in bladder volume at enuresis and it was lower than maximal voided volume in more than 50% of episodes. Variability in bladder volume at enuresis was greatest in the patient group with decreased bladder capacity. We found a significant correlation between diuresis and bladder capacity in all groups during the day and night. CONCLUSIONS: There is a great intra-individual diurnal variability in voided volume in children with enuresis and in healthy children. Enuresis seems to occur at bladder volumes that are smaller and larger than the maximal voided volume obtained from voiding charts.

Child↗
PubMed2006

The standardization of terminology of lower urinary tract function in children and adolescents: report from the Standardisation Committee of the International Children's Continence Society.

PURPOSE: We updated the terminology in the field of pediatric lower urinary tract function. MATERIALS AND METHODS: Discussions were held of the board of the International Children's Continence Society and an extensive reviewing process was done involving all members of the International Children's Continence Society as well as other experts in the field. RESULTS AND CONCLUSIONS: New definitions and a standardized terminology are provided, taking into account changes in the adult sphere and new research results.

Adolescent↗
PubMed2005

alpha-MSH prevents impairment in renal function and dysregulation of AQPs and Na-K-ATPase in rats with bilateral ureteral obstruction.

The purpose of this study was to evaluate the effects of the anti-inflammatory hormone alpha-melanocyte-stimulating hormone (alpha-MSH) treatment on renal function and expression of aquaporins (AQPs) and Na-K-ATPase in the kidney in response to 24 h of bilateral ureteral obstruction (BUO) or release of BUO (BUO-R). In rats with 24-h BUO, immunoblotting revealed that downregulation of AQP2 and AQP3 was attenuated (AQP2: 38 +/- 5 vs. 13 +/- 4%; AQP3: 44 +/- 3 vs. 19 +/- 4% of sham levels; P < 0.05), whereas downregulation of Na-K-ATPase was prevented by alpha-MSH treatment (Na-K-ATPase: 94 +/- 7 vs. 35 +/- 5% of sham levels; P < 0.05). Immunocytochemistry confirmed the changes in AQP1 and Na-K-ATPase expression. Renal tubular cell apoptosis was confirmed in BUO kidneys, and alpha-MSH treatment virtually completely abolished apoptosis. Furthermore, we measured glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively. Forty-eight hours after BUO-R demonstrated that alpha-MSH treatment almost completely prevented the decrease in GFR (nontreated: 271 +/- 50; alpha-MSH: 706 +/- 85; sham: 841 +/- 105 microl x min(-1).100 g body wt(-1), P < 0.05) and ERPF (nontreated: 1,139 +/- 217; alpha-MSH: 2,598 +/- 129; sham: 2,633 +/- 457 microl x min(-1).100 g body wt(-1), P < 0.05). alpha-MSH treatment also partly prevented the downregulation of AQP1 and Na-K-ATPase expression in rats after BUO-R for 48 h. In conclusion, alpha-MSH treatment significantly prevents impairment in renal function and also prevents downregulation of AQP2, AQP3, and Na-K-ATPase during BUO or AQP1 and Na-K-ATPase after BUO-R, demonstrating a marked renoprotective effect of alpha-MSH treatment in conditions with urinary tract obstruction.

Animals↗
PubMed2005

Endoluminal pelvic perfusion with norepinephrine causes only minor systemic effects and diminishes the increase in pelvic pressure caused by perfusion.

OBJECTIVE: To evaluate the effect of endoluminal norepinephrine (NE) on transport pressures of the normal upper urinary tract of the pig and on plasma levels of NE in relation to possible systemic effects. MATERIAL AND METHODS: Six anaesthetized pigs weighing approximately 39 kg were studied. Transparenchymally, two 6-F catheters were introduced into the renal pelvis bilaterally to measure pressure and perfusion. Ultrasonic flow probes recorded renal arterial blood flow, and a transurethral 10-F catheter drained the bladder and monitored diuresis. In all six animals, the bilateral pelvic pressure response was examined at increasing perfusion rates (2, 4, 6, 8, 10 and 15 ml/min) and with increasing doses of NE (0, 5, 50 and 100 microg/ml). Arterial blood samples were analysed for NE, epinephrine and blood glucose. The systemic blood pressure, heart rate and electrocardiogram were registered. RESULTS: At all the investigated concentrations, endoluminal NE significantly diminished the increase in pelvic pressure caused by pelvic perfusion at all flow rates. At the lowest concentration of NE, no significant increase in the plasma level of NE was observed and the blood pressure did not increase. During perfusion with 50 and 100 microg/ml NE, plasma levels of NE increased significantly from 487+/-398 to 1798+/-910 and 2961+/-2093 pg/ml, respectively. This was accompanied by significant rises in mean systolic blood pressure from a baseline value of 95+/-10 mmHg to 111+/-20 and 118+/-23 mmHg, respectively. Heart rate, renal arterial blood flow and plasma levels of epinephrine and glucose did not change. CONCLUSIONS: Endoluminal NE diminished the increase in pelvic pressure caused by pelvic perfusion even at concentrations too low to cause significant changes in NE plasma levels or systemic effects. Very high NE concentrations in the perfusion fluid caused increased plasma levels and a modest but significant increase in blood pressure. Administration of endoluminal NE may be useful in upper urinary tract stone treatment and endoscopy.

Adrenergic alpha-Agonists↗
PubMed2005

Clinical evaluation of a novel ultrasound-based bladder volume monitor.

OBJECTIVE: Bladder volume monitors may be useful for surveillance of bladder volume and urine production in urologic patients. Therefore, we designed an ultrasonic bladder volume monitor and evaluated it in vitro using phantoms and in vivo in one male volunteer. The purpose of this study was to perform a more thorough in vivo evaluation of our monitor in urologic patients to investigate biological effects and variance over a wide range of bladder volumes. MATERIAL AND METHODS: Thirty urologic patients of either gender were examined using the bladder volume monitor, which is based on seven phased array ultrasonic transducers arranged in a circular pattern to optimize detection of the bladder walls. The monitor was set up to record bladder volume every 30 s during two sequential cystometries with infusion rates of 30 and 60 ml/min. The measured volumes were analyzed using regression analysis to determine volume increments (slopes), offset volume (intercept) and correlation (Pearson's correlation coefficient). RESULTS: In the male patients, the median correlation coefficient between the infused and measured volumes was 0.97 and the slope was 0.68 ml/ml, thus warranting a correction factor of approximately 1.47 with no general volume offset. In the female patients, small bladders were generally outside the field of view of the monitor. Consequently, the correlation coefficients and slopes were 0.834 (median) and 0.43 (mean), respectively, whereas volume offsets were generally negative. CONCLUSIONS: For examinations in male patients, the performance of the bladder volume monitor was adequate. However, for examinations in female patients, a minor redesign of the transducer unit is necessary to insure proper operation.

Adult↗
PubMed2005

Stereotactic electrical stimulation of the pontine micturition centre in the pig.

OBJECTIVE: To apply stereotactic electrical stimulation of the pig brainstem and thus identify a pontine micturition centre. MATERIALS AND METHODS: In 10 anaesthetized female Vietnamese minipigs a needle-electrode was positioned in the pontine region. Pressure responses in the lower urinary tract identified the micturition centre functionally during electrical stimulation. Stereotactic coordinates were recorded, and the needle visualized by fluoroscopy, magnetic resonance imaging (MRI) or histologically. RESULTS: The stimulation evoked responses similar to voiding, i.e. a urethral pressure decrease followed by a bladder pressure increase; or similar to a continence manoeuvre, i.e. urethral pressure increase and no change in bladder pressure. In a few cases a continence response was evoked by stimulating a site 1 mm away from the site where a voiding response was evoked. The electrode position was detected by the fluoroscopy-based stereotactic procedure followed by subsequent MRI (one animal), and by histological analysis, verifying it to be in the dorsolateral pontine region. CONCLUSIONS: These results show that a pontine micturition centre exists in pigs similar to that described in rats, cats, dogs and humans.

Animals↗
PubMed2004

Pharmacokinetics and pharmacodynamics of desmopressin administered orally versus intravenously at daytime versus night-time in healthy men aged 55-70 years.

OBJECTIVE: To investigate (1) the pharmacokinetic and pharmacodynamic profiles of desmopressin in men from an age group with a high incidence of nocturia; and (2) circadian variation in the pharmacokinetic parameters. METHODS: The study had an open, randomised, four-way cross-over design. Desmopressin was administered orally (0.2 mg) and intravenously (2 microg), daytime and night-time, yielding four in-hospital sessions, separated by at least 2 days. Blood samples were taken before and at predetermined time points up to 12 h after dosing. Pharmacokinetic parameters were derived using a two-compartmental model except for AUC(0-->t), which was derived using non-compartmental analysis. Bioavailability was estimated using AUC(0-->t) for the oral and the intravenous periods. Urine, for measurements of volume and osmolality, was collected in predetermined intervals before and until 12 h after dosing. RESULTS: Fifteen healthy men aged 55-70 years were included in the analysis. The concentration-time curve after 2 microg intravenous desmopressin was best described using a biexponential term. The mean (95% CI) AUC at night was 302 (272-335) pg x h/ml and in the day was 281 (253-312) pg x h/ml. No statistically significant differences were detected between night and day except for terminal half-life, which was 3.1 h at night and 2.8 h in the daytime (P=0.02). After oral desmopressin, concentrations above the limit of quantification (2.5 pg/ml) were only detected in 51% of the samples. Peak plasma concentration (Cmax) was 6.2 (5.1-7.5) pg/ml at night and 6.6 (5.5-7.9) pg/ml in the daytime. Median time to reach Cmax (tmax) was 1.5 (range 1.0-4.1) h at night and 1.5 (range 0.5-3.0) h in the day. The bioavailability was 0.08%. The pharmacodynamic effects of oral and intravenous desmopressin given in the daytime were similar during the first 6 h after dosing. The night-time dosing and daytime intravenous dose resulted in antidiuresis throughout the measuring period, while the effect of the daytime peroral dose receded after 6 h. CONCLUSION: The pharmacokinetic profile of desmopressin is biexponential. Terminal half-life was longer at night than in the daytime, but the difference is considered too small to be of clinical importance. The plasma levels given by the intravenous dose resulted in a duration of action of 12 h or more. Despite low bioavailability, the pharmacodynamic effects of oral desmopressin were similar in magnitude to those after intravenous dose at night and during the first 6 h after daytime administration.

Administration, Oral↗
PubMed2004

Early release of neonatal ureteral obstruction preserves renal function.

The incidence of congenital hydronephrosis is approximately 1% and is often associated with renal insufficiency. It is unknown whether early release is essential to prevent deterioration of renal function. Rats were subjected to partial unilateral ureteral obstruction (PUUO) on postnatal day 2. The obstruction was left in place or released after 1 or 4 wk. Renal blood flow (RBF) and kidney size were measured sequentially over 24 wk using MRI. In rats in which the obstruction was left in place, RBF of the obstructed kidney was progressively reduced to 0.92 +/- 0.17 vs. 1.79 +/- 0.12 ml.min(-1).100 g body wt(-1) (P < 0.05) after 24 wk. Similarly, glomerular filtration rate of the obstructed kidney was severely reduced at 24 wk: 172 +/- 36 vs. 306 +/- 42 microl.min(-1).100 g body wt(-1) (P < 0.05). These changes were preceded by development of severe hydronephrosis and obstructive nephropathy with a reduction in total protein content: 45 +/- 3 vs. 58 +/- 4 mg/kidney. Moreover, nonreleased PUUO caused a marked natriuresis (0.32 +/- 0.07 vs. 0.11 +/- 0.02 micromol.min(-1).100 g body wt(-1), P < 0.05) and impaired solute free water reabsorption (0.47 +/- 0.16 vs. 2.71 +/- 0.67 microl.min(-1).100 g body wt(-1), P < 0.05), consistent with a significant downregulation of Na-K-ATPase to 62 +/- 7%, aquaporin-1 to 53 +/- 3%, and aquaporin-3 to 53 +/- 7% of sham levels. Release after 1 wk completely prevented development of hydronephrosis, reduction in RBF and glomerular filtration rate, and downregulation of renal transport proteins, whereas release after 4 wk had no effect. These results suggest that early release of neonatal obstruction provides dramatically better protection of renal function than release of obstruction after the maturation process is completed.

Aging↗
PubMed2004

Quantitation of differential renal blood flow and renal function using dynamic contrast-enhanced MRI in rats.

A first-pass upslope approach was used to estimate differential renal blood flow (DRBF) and a Patlak-Rutland approach was used to estimate differential renal function (DRF) using Gd-DTPA-BMA-enhanced MRI. DRBF and DRF were estimated in rat kidneys under three different experimental conditions: 1) transient renal artery occlusion (TRAO); 2) partial unilateral ureteric obstruction (PUO); and 3) sham-operated control rats (SHAM). A bolus of Gd-DTPA-BMA was given intravenously during a dynamic single slice T1-weighted gradient echo sequence, which allowed calculation of concentration from signal intensity values. Calculations based on the raw signal intensity showed that DRBF was decreased in both PUO (44 +/- 1%; P < 0.05) and in TRAO (38 +/- 1%; P < 0.05) compared with SHAM (52 +/- 1%). Converting the signal intensity into a measure of Gd-DTPA-BMA concentration did not substantially alter these findings (PUO: 40 +/- 3%, P < 0.05; TRAO: 35 +/- 2%, P < 0.05; SHAM 49 +/- 1%). Likewise, DRF decreased in both PUO (43 +/- 4%; P < 0.05) and TRAO (39 +/- 3%; P < 0.05) compared with SHAM (48 +/- 2%). Converting the signal intensity into measurements of Gd-DTPA-BMA concentration revealed similar findings (PUO: 41 +/- 5%, P < 0.05; TRAO: 34 +/- 5%, P < 0.05; SHAM: 49 +/- 2%). Our results suggest that renal damage in rats may be demonstrated by an observed reduction of DRBF and DRF as estimated from single-slice Gd-DTPA-BMA enhanced signal intensity using time-activity curves with and without quantitation of Gd-concentration.

Analysis of Variance↗
PubMed2004

MRI assessment of the influence of body position on the shape and position of the urinary bladder.

OBJECTIVE: Continuous surveillance of patients' bladder volume may be of benefit during the treatment of various urologic disorders. In order to design optimal bladder volume monitoring equipment, information about the shape and position of the bladder, not at least in relation to posture, is crucial. The purpose of this study was consequently to evaluate the influence of body position on the change in shape and position of the bladder. MATERIAL AND METHODS: MRI was performed in three young volunteers during posture changes. MRI scans in the transverse, frontal and sagittal planes were recorded in bladders of various sizes. The position of the bladder midpoint in the three planes was determined. Moreover, to account for its shape, the compactness of the cross-section of the bladder was calculated on the basis of its perimeter and area. RESULTS: For the medial-lateral and cranial-caudal positions, the maximal displacements were 4 and 5 mm, respectively. In the ventral-dorsal direction the displacement varied, but was <18 mm. The compactness changed maximally by 11%, indicating a minimal change in shape. CONCLUSION: In young subjects, the position and shape of the bladder only change modestly for different body positions, thus eliminating the need for special correction measures when designing bladder volume monitoring equipment.

Adult↗
PubMed2004

Effect of bladder volume, gender and body position on the shape and position of the urinary bladder.

OBJECTIVE: The optimal design of bladder volume-monitoring equipment, e.g. regarding transducer design and software algorithms, depends greatly on the shape and position of the bladder or on potential changes due to body position and bladder volume. The purpose of this study was to study the influence of body position, bladder volume and gender on the shape and position of the bladder. MATERIAL AND METHODS: MRI scans of 11 young volunteers were performed during changes in posture. Images were recorded in the transverse and frontal planes and repeated four to six times through the bladder-filling cycle from empty to full. The position of the bladder midpoint was measured in the three planes. Moreover, to account for shape, the compactness of the cross-section of the bladder was calculated based on its perimeter and area. The effect of body position and gender was analyzed using repeated-measures ANOVA and the independent samples t-test, respectively. RESULTS: No significant effect of body position on bladder position or shape was found. Gender was shown to have a significant impact on both the position and shape of the bladder: the female bladder was positioned more caudally and was less compact in the transverse plane than the male bladder. Furthermore, there was significant cranial-dorsal movement of the bladder during filling. CONCLUSION: No significant changes in the position or shape of the bladder were observed during changes in body position in young subjects, regardless of bladder volume or gender. However, changes in both parameters were found due to bladder filling.

Adult↗
PubMed2004

Neonatal ureteral obstruction alters expression of renal sodium transporters and aquaporin water channels.

BACKGROUND: Congenital urinary tract obstruction is a common cause of renal insufficiency in the neonate and during infancy. Recently, we demonstrated that ureteral obstruction in adult rats is associated with reduction in the abundance of renal aquaporins (AQPs) and renal sodium transporters, which paralleled an impaired urinary concentrating capacity. METHODS: In the present study, renal handling of sodium and water, together with the expression of renal aquaporins and major renal sodium transporters, was examined in rats with neonatally induced partial unilateral ureteral obstruction (PUUO) within the first 48 hours of life to clarify the molecular mechanisms involved in the tubular functional defects in response to congenital obstruction. Rats were then followed for 12 or 24 weeks. RESULTS: Neonatal PUUO caused a progressive reduction in single kidney glomerular filtration rate (SKGFR) on the obstructed side to 43% of controls at 12 weeks (115 +/- 28 vs. 267 +/- 36 microL/min/100g bw, P < 0.05), and 31% of controls at 24 weeks (106 +/- 24 vs. 343 +/- 41 microL/min/100g bw, P < 0.05). Na-K-ATPase abundance was decreased in the obstructed kidney compared with the nonobstructed kidney at 24 weeks (79 +/- 6%, P < 0.05), and the abundance of bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1) located to the medullary thick ascending limb (mTAL) of the obstructed kidney was significantly reduced both at 12 weeks (42 +/- 10%, P < 0.05) and 24 weeks (50 +/- 10%, P < 0.05). Immunohistochemistry confirmed down-regulation of BSC-1 both at 12 and 24 weeks after onset of obstruction. Consistent with this, sodium excretion from the obstructed kidney was increased at 12 weeks (0.13 +/- 0.03 vs. 0.04 +/- 0.01 micromol/min/100g bw, P < 0.05), and persisted 24 weeks after onset of PUUO (0.15 +/- 0.02 vs. 0.06 +/- 0.01 micromol/min/100g bw, P < 0.05). AQP2 abundance in the collecting duct was also reduced both at 12 weeks (68 +/- 5%, P < 0.05) and at 24 weeks (69 +/- 13%, P < 0.05). Consistent with this, solute-free water reabsorption was decreased in the obstructed kidney at 12 weeks (0.61 +/- 0.42 vs. 1.97 +/- 0.63 microL/min/100g bw, P < 0.05) and remained decreased after 24 weeks of PUUO (0.42 +/- 0.04 vs. 1.56 +/- 0.39 microL/min/100g bw, P < 0.05). CONCLUSION: Major sodium transporters and aquaporins in the obstructed kidney are down-regulated in response to neonatally induced PUUO, which indicates that these transporters may play a crucial role for the persistent reduction in renal handling of sodium and water in response to PUUO.

Animals↗