Unilateral Ureteral Obstruction Animals Research Articles

Effects of Chronic Pain Following Unilateral Ureteral Obstruction on Hippocampal CA1 Pyramidal Neurons in Male Wistar Rats

Background: Chronic pain can adversely affect cognitive functions such as learning, memory, and attention. However, the precise mechanisms underlying cognitive impairment in chronic pain remain elusive. Objectives: This study aims to investigate the impact of chronic pain induced by unilateral ureteral obstruction (UUO) on hippocampal neurons. Methods: In the current case-control study, 27 male Wistar rats (230 - 280 g) were randomly assigned to three groups: 1-sham, 2-UUO, and 3-UUO treated with naloxone (i.p.; 1 mg/kg for 5 days). Following transcardial perfusion, the rats' brains were removed, and histological studies were performed to count the number of neurons using an optical microscope. Concurrently, TNF-α and NGF levels were measured in brain tissue homogenate. Results: The mean number of neurons in the CA1 region of the animals in the UUO group was 68.11 ± 1.34, which showed a significant decrease compared to the mean number of neurons in the sham-operated group (114.1 ± 1.77; P < 0.0001). In contrast, the mean number of neurons in the CA1 region of the UUO with naloxone group showed a significant increase compared to the animals in the UUO group (73.44 ± 1.37; P < 0.0001). TNF-α was 264.3 ± 2.6 pg/mL in the UUO animals and decreased significantly in the UUO animals treated with naloxone (P = 0.001). However, NGF was 115.2 ± 2.9 pg/mL in UUO animals and increased significantly in the UUO with naloxone group (P < 0.01). Conclusions: Unilateral ureteral obstruction, through inducing chronic pain and inflammation, resulted in neurodegeneration in the CA1 region of the hippocampus. The use of naloxone, an opioid antagonist, immediately after the surgery was able to provide neuronal protection and an anti-inflammatory effect.

Wingless/int-1induced secreted protein-1: a new biomarker for renal fibrosis.

This study aimed to detect the expression of Wnt-induced secreted protein-1 (WISP-1) in renal fibrosis (RF) and to clarify the underlying mechanism. An in vivo mousee model of unilateral ureteral obstruction (UUO) and in vitro model of fibrosis on renal tubular epithelial NRK52E cells after transforming growth factor-β1 (TGF-β1) stimulation were used. Quantitative real-time PCR (qRT-PCR), Western blot (WB), and immunohistochemistry were used to detect WISP-1 and fibrosis markers, including the expression of fibronectin (FN), collagen I (Col I), collagen IV (Col IV), and α-smooth muscle actin (α-SMA). In vitro experiments showed that the expression of WISP-1 and fibrosis markers FN, Col I, Col IV, and α-SMA in rat renal tubular epithelial cells were significantly higher than that in the control group after 48 h of TGF-β1 stimulation. In vivo experiments showed that the expressions of WISP-1 and fibrosis markers FN, Col I, Col IV, and α-SMA in the obstructed kidney of UUO animal models were significantly increased in mRNA and protein levels compared to normal mice. This study showed that WISP-1 may be an essential cytokine that promotes renal fibrosis, being involved in the development of renal fibrosis.

Riociguat ameliorates kidney injury and fibrosis in an animal model

Chronic kidney disease (CKD) is one of the greatest health burdens with an increasing global prevalence. Renal fibrosis (RF) is the hallmark of all forms of CKD which shows a strong positive correlation with severity of the disease. However, there are no therapeutic options available for treatment of RF. In the present study, we used an animal model based on unilateral ureteral obstruction (UUO), for renal injury and fibrosis. The UUO animals were treated with soluble guanylyl cyclase (sGC) stimulator, riociguat (RIO) (1, 3 and 10 mg/kg) to investigate its possible renoprotective effects. Kidneys of animals treated with RIO were found to show less abnormalities as compared to UUO control. Further, the levels of proinflammatory cytokines were reduced in RIO treated group. Furthermore, administration of RIO reduced expression of collagen-1, TGF-β, CTGF, α-SMA, vimentin along with transcription factors including Snail and Slug. The results of the present study provided strong evidence to support the antifibrotic activity of RIO.

Metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice.

Metformin is today the first choice treatment for type‐2 diabetes, but has also protective effects in several renal disease models. Previously, we have demonstrated that the protective effects in response to unilateral ureteral obstruction (UUO) are independent of organic cation transporters (OCTs), the transporters responsible for the metformin uptake into the renal cells. The mechanisms behind the renoprotective effects are incompletely understood, but our previous results indicate that the renoprotective effects at least partly could be dependent on actions of metformin outside the renal cells. In this study, we investigate whether the renoprotective effects of metformin can be mediated via systemic immunomodulatory actions. We demonstrated that metformin can affect the immune system in the kidney as well as in the peripheral blood and spleen following UUO. UUO kidneys showed infiltration of immune cells including monocytes, B cells, and T cells, but metformin limited infiltration of all cell types. UUO animals had increased spleen sizes, but this increase was attenuated by metformin. Metformin treatment surprisingly resulted in a higher proportion of monocytes with infiltratory capacity 7 days after UUO. Other studies have suggested that metformin regulates monocyte maturation through signal transducer and activator of transcription 3 (STAT3) activation, as also indicated by our results. In conclusion, our results demonstrate that metformin limits the infiltration of immune cells into the kidney, as well as modulates immune cell composition at a systemic level.

PNaKtide ameliorates renal interstitial fibrosis through inhibition of sodium-potassium adenosine triphosphatase-mediated signaling pathways in unilateral ureteral obstruction mice.

Sodium-potassium adenosine triphosphatase (Na/K-ATPase) has been shown to regulate Src activity by combining with Src to keep it in an inactive form. We previously reported that Na/K-ATPase was downregulated in unilateral ureteral obstruction (UUO) animals. In this study, we examined whether inhibition of Na/K-ATPase-mediated Src signaling pathways ameliorated renal interstitial fibrosis induced by UUO. UUO was performed on male C57BL/6J mice. pNaKtide, a mimic of Na/K-ATPase, was administered by intraperitoneal injection on Day 0 and Day 4 after ureteral ligation. Markers of interstitial fibrosis, inflammation and oxidative stress and transforming growth factor-β1 (TGF-β1) expression were examined after the mice were sacrificed on Day 7. Activation of Src and its downstream signaling effectors, including extracellular regulated protein kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK) and protein kinase B (AKT), were evaluated. pNaKtide administration markedly attenuated myofibroblast accumulation and extracellular matrix deposition in obstructed kidneys. Also, pNaKtide significantly reduced the increased expression of 8-iso-prostaglandin F2α, TGF-β1, interleukin-6 and monocyte chemoattractant protein-1 (MCP-1), as well as reduced macrophage infiltration, in UUO animals. All these changes were obtained, along with inhibition of Src and its downstream effector activity. Na/K-ATPase-mediated signaling pathways contribute to fibrogenesis and could represent a potential target in the treatment of renal fibrosis.

N-acetylcysteine ameliorates contrast‑induced kidney injury in rats with unilateral hydronephrosis.

The aim of the present study was to investigate the protective effects of N-acetylcysteine (NAC) on contrast-induced acute kidney injury in rats with unilateral hyronephrosis. Eighty-two male Sprague Dawley rats were randomized to undergo sham operation (n=14) or unilateral ureteral obstruction (UUO) (n=68). After 3 weeks, the UUO animals were randomized to three groups: NAC gastric perfusion, UUO+iohexol+NAC (n=24); normal saline perfusion, UUO+iohexol (n=24); and controls, UUO (n=20). After 3 days, UUO+iohexol+NAC and UUO+iohexol rats were injected with iohexol. One day after contrast, half of the rats were sacrificed to assess the pathological changes to the kidneys, serum creatinine, serum neutrophil gelatinase-associated lipocalin (NGAL), renal cell apoptosis rate and expression of apoptosis regulators Bcl-2/Bax. The remaining rats underwent obstruction relief and were analyzed 3 weeks later. Compared with the controls, serum NGAL levels were high in UUO+iohexol rats 1 day following injection and 3 weeks after obstruction relief, but UUO+iohexol+NAC rats exhibited lower serum NGAL levels compared with UUO+iohexol rats (all P<0.05). Following modeling, UUO+iohexol rats exhibited a significantly higher apoptosis rate of renal tubular cells, higher expression of Bax mRNA, and lower ratio of Bcl-2/Bax (all P<0.05). Three weeks after obstruction relief, UUO+iohexol+NAC rats exhibited a lower apoptosis rate, lower Bax mRNA expression, higher expression of Bcl-2 mRNA and higher ratio of Bcl-2/Bax (all P<0.05) compared with day 1 following drug administration. The prophylactic use of NAC reduced the apoptotic rate of renal tubular cells following contrast exposition, which was accompanied by changes in the expression of Bcl-2/Bax mRNA.

Regulation of eIF2α expression and renal interstitial fibrosis by resveratrol in rat renal tissue after unilateral ureteral obstruction

Purpose This study was performed to assess the effect of resveratrol on the expression of eukaryotic initiation factor 2α (eIF2α) and activating transcription factor 4 (ATF4) in renal tissues of rats with unilateral ureteral obstruction (UUO). Methods Using UUO animal model, after 14 days of surgery, pathological changes were detected by HE staining, renal tubular damage index, renal interstitial collagen deposition area were evaluated by Masson staining, in situ cell apoptosis in renal tissue was analyzed by TUNEL assay, and protein expression of eIF2α and ATF4 in renal tissue was analyzed using western blot detection. Results After comparison of the treatment groups with model group, we observed that the degree of renal tubular damage, relative area of renal interstitial collagen and eIF2α, ATF4 protein expression were also significantly reduced (p<0.05, p <0.01) in the high-dose resveratrol group. Conclusion Resveratrol can reduce the level of eIF2α protein expression, which further reduces the ATF4 levels.

Effect of angiotensin II and small GTPase Ras signaling pathway inhibition on early renal changes in a murine model of obstructive nephropathy.

Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and α-smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling system and decreased the early fibrotic response in the obstructed kidney. This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis.

Urokinase-type plasminogen activator receptor in IgA nephropathy

Urokinase-type plasminogen activator receptor in IgA nephropathy

Low-Level Laser Therapy Decreases Renal Interstitial Fibrosis

the purpose of this study was to investigate the effect of low-level laser therapy (LLLT) on chronic kidney disease (CKD) in a model of unilateral ureteral obstruction (UUO). Regardless of the etiology, CKD involves progressive widespread tissue fibrosis, tubular atrophy, and loss of kidney function. This process also occurs in kidney allograft. At present, effective therapies for this condition are lacking. We investigated the effects of LLLT on the interstitial fibrosis that occurs after experimental UUO in rats. The occluded kidney of half of the 32 Wistar rats that underwent UUO received a single intraoperative dose of LLLT (AlGaAs laser, 780 nm, 22.5 J/cm(2), 30 mW, 0.75 W/cm(2), 30 sec on each of nine points). After 14 days, renal fibrosis was assessed by Sirius red staining under polarized light. Immunohistochemical analyses quantitated the renal tissue cells that expressed fibroblast (FSP-1) and myofibroblast (α-SMA) markers. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to determine the mRNA expression of interleukin (IL)-6, monocyte chemotactic protein-1 (MCP-1), transforming growth factor (TGF)-β1 and Smad3. The UUO and LLLT animals had less fibrosis than the UUO animals, as well having decreased expression inflammatory and pro-fibrotic markers. For the first time, we showed that LLLT had a protective effect regarding renal interstitial fibrosis. It is conceivable that by attenuating inflammation, LLLT can prevent tubular activation and transdifferentiation, which are the two processes that mainly drive the renal fibrosis of the UUO model.

Taxol and Taurine Protect the Renal Tissue of Rats after Unilateral Ureteral Obstruction: A Stereological Survey

PurposeBlockage of the urinary tract induces changes in renal structure including tubular dilatation or atrophy, tubular cell death, inflammatory processes, and progressive interstitial fibrosis with the loss of renal parenchyma. The present study was conducted to survey the protective effects of Taxol and taurine on the renal structure after unilateral ureteral obstruction (UUO).Materials and MethodsUUO was induced in three groups of rats (n=6) who then received distilled water, Taxol (0.3 mg/kg/d), or taurine (7.5 mg/kg/d). Stereological methods were used to gather quantitative as well as comparative data.ResultsLess than -8% of the volume of the glomeruli, proximal convoluted tubules (PCT), distal convoluted tubules (DCT), Henle's loop, and collecting ducts were preserved after UUO. After treatment of the UUO rats with Taxol, between -32% and 88% of the parameters mentioned above remained intact, and after treatment of the UUO rats with taurine, between -16% and 46% of the parameters remained intact (p<0.01). Compared with the untreated UUO animals, the volume of necrotic and fibrotic tissues decreased -53% and -63% in the UUO rats treated with Taxol and taurine, respectively (p<0.01). Less than -3% of the lengths of the renal tubules (PCT, DCT, Henle's loop, and collecting) were preserved in the UUO rats. After treatment with Taxol and taurine, -61% to 70% and -43% to 53% of the length of the renal tubules were preserved, respectively (p<0.01).ConclusionsTaurine and Taxol are effective in preventing some structural renal damage in a direct ureteral obstruction model. Taxol was more effective in renal protection.

Activation of ERK in renal fibrosis after unilateral ureteral obstruction: Modulation by antioxidants

A recent in vitro model of oxidative stress-induced renal fibrosis demonstrated that activated or phosphorylated extracellular signal-regulated protein kinase (pERK) played a role in apoptosis of renal fibroblasts, but not tubular epithelium where it promoted cell growth and survival. The present study utilized an in vivo model of renal fibrosis after unilateral ureteral obstruction (UUO) to examine the relationship between pERK, apoptosis, proliferation, and differentiation in renal fibroblast and tubular epithelial cells, in comparison with the in vitro results. UUO was induced in rats for 0 (controls, untreated), 6, and 24 hours, 2, 4, and 7 days (N= 4), and tissue analyzed for fibrotic characteristics using microscopy and special stains, Western immunoblots and reverse transcription-polymerase chain reaction (RT-PCR). Controls and UUO animals were also treated with vitamin E, N-acetylcysteine (NAC), or fluvastatin to assess any antioxidant effect on attenuation of fibrosis and pERK expression. Azan stain and alpha-smooth muscle actin (alpha-SMA), collagen III, and fibronectin expression confirmed development of UUO-induced fibrosis. Oxidative stress markers heme oxygenase-1 (HO-1) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) confirmed oxidative stress at all UUO time points. Tubular epithelial and interstitial mitosis and apoptosis were significantly increased over controls at 2 to 7 days after UUO (P < 0.01). The pERK/ERK ratio increased significantly at 1 to 7 days of UUO in comparison with controls (three- to fivefold, P < 0.05). There was a significant spatiotemporal correlation between pERK and tubular epithelial proliferation (P < 0.001). pERK occasionally colocalized with apoptotic cells (dual labeling) in the interstitium but not in the tubular epithelium. Fluvastatin was the only treatment that attenuated fibrosis (decreased alpha-SMA, fibronectin, tubular epithelial apoptosis) and it also significantly decreased expression of 8-OHdG at 2 and 7 days (P < 0.05). It was associated with decreased pERK at 7 days, compared with UUO alone (P < 0.05). Promotion of tubular epithelial proliferation and survival, and interstitial cell apoptosis, may minimize renal fibrosis after UUO. In the present study, both were linked spatially and temporally with increased pERK expression. Fluvastatin treatment attenuated UUO-induced fibrosis via an antioxidant and pERK-related mechanism.

A functional immature model of chronic partial ureteral obstruction

The most common nonlethal congenital anomaly of the urinary tract is ureteral obstruction without dysplasia. Although rarely progressive, the morbidity associated with metabolic and surgical management is considerable. Our study was designed to measure local and systemic pathophysiologic mechanisms in an immature model of chronic partial unilateral ureteral obstruction (UUO) after completion of glomerulogenesis. A partial UUO was created by the method of "psoas wrap" in young male weanling rats. Control animals were sham operated. Three groups were divided as follows: sham (N= 15), UUO (N= 18), and UUO + angiotensin-converting enzyme (ACE) (N= 16) inhibitor, enalapril. Renal glomerular and tubular functions were determined by creatinine and uric acid clearances. Diuresis was assessed by urine volume, osmolality, and fractional solute excretions from samples above and below the obstruction. Proteinuria was determined by the urine protein/creatinine ratio (Up/c). Proteinuria was attenuated in UUO + ACE-treated animals. The hyperuricemia of the immature UUO animals was avoided by an increase in the clearance of uric acid in the UUO + ACE-treated group. Fractional solute excretions suggested a diversion of diuresis to the contralateral unobstructed kidney. Angiotensin blockade during chronic UUO in young rats affords protection by attenuating proteinuria, promoting uricosuria, and diverting solute diuresis. These data suggest a complex interaction of local and systemic mechanisms unique to the maturing kidney.

Alpha-tocopherol modulates lipoprotein cytotoxicity in obstructive nephropathy.

Oxidative stress in unilateral ureteral obstruction (UUO) contributes to the development of glomerular and tubulointerstitial lesions. The present study investigated whether oxidized low-density lipoprotein (oLDL) contributes to the pathogenesis of kidney injury in UUO, and whether alpha-tocopherol modulates such cytotoxicity and promotes repair. Male Sprague-Dawley rats weighing 100-125 g were assigned to three groups of 6 animals each: (1) sham, regular chow; (2) UUO, regular chow; and (3) UUO, alpha-tocopherol supplementation. We found a significant increase in the level of oxidative stress in the UUO group as measured by malondialdehyde (MDA) content in both plasma and kidneys. The LDL isolated from this group was cytotoxic to rat mesangial cells. The level of oxidation and cytotoxicity was significantly reduced when animals were treated with alpha-tocopherol. Plasma cholesterol concentration, kidney MDA, and transforming growth factor beta1 mRNA expression were all significantly increased in the UUO animals, and partially reduced in alpha-tocopherol-treated animals. Our data suggest that oxidative modification of LDL is associated with the renal injury in UUO. Taken together, our data support the concept that alpha-tocopherol can modulate LDL oxidation and its cytotoxic effects on rat mesangial cells in vitro.

Increased Heat Shock Protein-70 in Unilateral Ureteral Obstruction in Rats

Our previous studies noted the oxidative stress of unilateral ureteral obstruction (UUO). Now, we seek to explore whether UUO affects the intrinsic cellular antioxidants and triggers heat shock protein (HSP-70) and whether these are still highly expressed after reversal of the UUO (R-UUO). In addition, we designed the experiment to determine whether this expression of HSP-70 is a localized or a generalized response. Male Sprague–Dawley rats (125–150 g) were randomly assigned to sham operation, left UUO, or R-UUO procedures at six rats per group. The sham, UUO, and R-UUO animals were studied 10 days after UUO or 7 days after R-UUO. A clear increase in the left (obstructed) kidney's malondialdehyde (MDA), a marker of lipid peroxidation, was observed: a significant 2.6-fold of sham during UUO and a 1.7-fold of sham in R-UUO. The contralateral (unobstructed) right kidney showed a significant rise in MDA during UUO, but during R-UUO the MDA had fallen back to sham values. It is possibly the result of a systemic effect from the free radicals produced by the oxidative stress of the UUO. The antioxidant enzyme, manganese superoxide dismutase (MnSOD) of the left, obstructed kidney showed a significant reduction in UUO compared to that of the sham. Upon reversal of UUO (R-UUO), MnSOD was lower than that of the sham. The left kidney's HSP-70 increased during UUO and was 3.7-fold that of sham (P< 0.05) but, during R-UUO, was not different from sham (P,ns). The contralateral (intact) right kidneys' HSP-70 showed no change between sham, UUO, and R-UUO states. We conclude that UUO gives rise to oxidative stress which is generalized in both the obstructed and the contralateral unobstructed kidney, as indicated by the elevation in kidney MDA content in both kidneys. The intrinsic cellular antioxidant enzyme, manganese superoxide dismutase, showed a significant and generalized reduction in both UUO and R-UUO. In contrast, the HSP-70 was markedly elevated only in the obstructed kidney and not in the R-UUO or in the contralateral kidney, suggesting that the elevation of HSP-70 is a specific and localized response to oxidative injury of UUO.

Inhibition of Transforming Growth Factor β1 Induction by Dietary Vitamin E in Unilateral Ureteral Obstruction in Rats

Free radical species associated with bilateral ureteral obstruction (BUO) are considered important in the pathogenesis of the glomerular and tubulointerstitial injury in BUO rats. We seek to test the hypothesis that the use of an easily administered antioxidant, vitamin E, at sufficient plasma concentrations, can decrease this release of free oxygen radicals in kidney tissue and ameliorate the increase of the fibrogenic cytokine, transforming growth factor β-1 (TGFβ-1). We used the unilateral ureteral obstruction (UUO) rat model, because the presence of the uninjured contralateral kidney provides a nonuremic internal milieu, in contrast to the uremic, acidotic, and hypercholesterolemic BUO model. Compared to sham controls, the UUO animals showed a dramatic increase in renal cortical TGFβ-1 mRNA, as quantitated by Northern blot analysis with cyclophilin internal standards. This increase in TGFβ-1 mRNA was reversed in UUO rats treated with vitamin E. The plasma malondialdehyde (MDA) concentration, an index of lipid peroxidation and an indirect index of free radical release, was significantly elevated in UUO animals compared to sham animals. The vitamin E-treated UUO animals showed a significant decrease in both plasma and renal cortical tissue MDA content. Taken together, these findings provide evidence of the important biological role of reactive free radical species in the tubulointerstitial injury of UUO and the novel role of vitamin E in modulating the mRNA of the fibrogenic TGFβ-1 in obstructive uropathy.

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

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- (tCl) 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 tCl 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 effect. The increased renal pressure may partly contribute to the defects in Na+ and K+ transport in the CCD from obstructed kidneys. Renal decapsulation has protective effects on impaired Na+ and K+ transports in the CCD after ureteral obstruction.

Hydraulic water permeability and transepithelial voltage in the isolated perfused rabbit cortical collecting tubule following acute unilateral ureteral obstruction.

Ureteral obstruction affects the kidney's ability to conserve water and sodium. Using the isolated perfused tubule technique, we studied cortical collecting tubules (CCT) taken from rabbits subjected to a sham operation or to 4 h of unilateral ureteral obstruction (UUO). Tubules were perfused in the presence of an osmotic gradient directed to promote water movement from lumen to bath, and volume flux (Jv), hydraulic water permeability (Lp), and transepithelial voltage (V1) were determined. In tubules from sham-operated and UUO animals, basal (before exposure to vasopressin) J, and Lp were not different from zero. After addition of 200 microU . ml-1 of arginine vasopressin (aVP) to the bath, Jv and Lp increased to 1.64 +/- 0.23 nl . mm-1 . min-1 and 127.9 +/- 19.8 cm . s-1 . atm-1 x 10(7), respectively, in tubules from sham-operated animals, but not only 0.27 +/- 0.09 nl . mm-1 . min-1 an 18.8 +/- 6.2 cm . s-1 . atm-1 . 10(7) in tubules from UUO animals. Pretreatment with desoxycorticosterone acetate (DOCA) or indomethacin in vivo did not prevent the blunted vasopressin response seen in tubules taken from UUO animals. The Jv and Lp responses to the cyclic AMP (cAMP) analogue, 8-Br-cAMP, were also diminished in tubules taken from UUO animals compared with shams. V1, measured during the basal period, was diminished in tubules from UUO kidneys (-5.0 +/- 2.1 mV) compared with shams (-21.9 +/- 4.1 mV), and pretreatment with DOCA did no prevent the effects of UUO on V1. In contrast, tubules taken from animals that received indomethacin prior to UUO developed voltages not different from voltages in tubules taken from sham-operated animals (-17.3 +/- 1.7 mV). We conclude that, although CCT from UUO animals can maintain osmotic gradients, their ability to respond to vasopressin by increasing Lp is impaired by an intrinsic defect located at a step beyond the generation of cAMP, and that prostaglandin inhibition or DOCA pretreatment do not reverse the decreased responsiveness of Lp to aVP. UUO also diminished V1, and this abnormality was prevented by previous treatment with indomethacin, suggesting that prostaglandins may mediate the effect of UUO on V1.