Functional and molecular evaluation of using aliskiren during acute and chronic partial ureteral obstruction in rat solitary kidney.

AIMS: To study the effect of direct renin inhibitor (aliskiren) on the renal function during acute and chronic partial ureteral obstruction (PUO) in rat solitary kidney. MAIN METHODS: Sixty male Sprague-Dawley rats were randomly allocated into three groups (20 rats each); sham, PUO and aliskiren groups. Right nephrectomy was performed in all groups. Rats in PUO and aliskiren groups were subjected to left PUO and received no treatment and aliskiren (10 mg/kg, orally, once per day till sacrification), respectively. Blood samples were then collected for biochemical measurements. Ten rats from each group were sacrificed after two weeks, while the remaining rats were sacrificed after four weeks. Left kidneys were harvested for histopathological examination, BCL-2, interleukin (IL)-6, transforming growth factor (TGF)-ß1, collagen I and fibronectin relative gene expression and assessment of glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) activity. KEY FINDINGS: After two and four weeks of PUO, aliskiren significantly recompensed the rise of serum creatinine (Scr) and blood urea nitrogen (BUN). Aliskiren also revealed significantly better histopathological results regarding cortical and medullary necrosis, regeneration and inflammatory cell infiltration. Aliskiren group showed statistically significant up-regulation of BCL-2 and down-regulation of IL-6, TGF-ß1, collagen I and fibronectin relative gene expression. Aliskiren significantly increased GSH and SOD activity and reduced MDA and NO activity. Moreover, aliskiren administration for four weeks after PUO significantly yielded more renoprotective effect compared to its administration for two weeks. SIGNIFICANCE: Aliskiren ameliorates the deterioration of the renal function during acute and chronic PUO in a solitary kidney.

Protective effects of ghrelin on kidney tissue in rats with partial ureteral obstruction

Background/aim: The aim was to investigate the protective and therapeutic effects of ghrelin, which has antioxidant and antiinflammatory activity, on preventing kidney damage that occurs by induced partial ureteral obstruction in rats Materials and methods: Twenty-eight adult male rats were included in the study, and the rats were divided into 4 groups. After the laparotomy operation on the sham group, the ureter was identified in the retroperitoneal area and was duly sutured (n = 7). Ghrelin was administered for seven days intraperitoneally, and after the nephrectomy performed on the 15th day, the rats were sacrificed (n = 7). A partial ureteral obstruction was performed after the laparotomy on the PUO group. The rats were sacrificed after the nephrectomy operation performed on the 15th day (n = 7). A partial ureteral obstruction was formed after the laparotomy followed by seven days of waiting in the PUO + ghrelin group. Ghrelin was given in the dose of 10 ng/kg per day intraperitoneally for the next 7 days, and the rats were sacrificed after the nephrectomy operation performed on the 15th day (n = 7). All groups were evaluated for histological damage and catalase, superoxide dismutase, total glutathione, malondialdehyde, and myeloperoxidase levels were measured in the same tissues Results: When the 2nd group and the sham group were compared histologically, it was observed that the damage had increased by a statistically significant level in the partial ureteral obstruction group (P = 0.001). When the group which was ghrelin-treated after the partial ureteral obstruction was compared to the group with just partial ureteral obstruction, the histopathological changes were found to decrease significantly in that group (P = 0.001). While the statistical significance of the levels of CAT, GSH, and MPO enzymes was detected among biochemical changes in the 2nd group when compared to the sham group (P < 0.01), the 3rd group showed a statistically significant difference in the levels of SOD and GSH enzymes compared to the 4th group (P < 0.05). Conclusion: Ghrelin administration to rats after the formation of an experimental partial unilateral ureteral obstruction reduces tissue damage due to ghrelin's antiinflammatory and antioxidant effects. Ghrelin administration may prevent tissue damage biochemically and histopathologically in obstructive uropathy cases

Pentoxifylline protects against loss of function and renal interstitial fibrosis in chronic experimental partial ureteral obstruction.

Tubulointerstitial fibrosis (TIF) is a hallmark of chronic kidney disease resulting from diverse etiologies and predicts severity and progression of the kidney disease. To investigate the pathogenesis of TIF, complete unilateral ureteral obstruction (UUO) is the most widely used animal model. However, UUO precludes evaluation of renal function. In the present study, we created a rat model of chronic partial ureteral obstruction (PUO), which allowed assessment of renal function at different intervals after obstruction. We examined the effects of pentoxifylline (PTF), a phosphodiesterase inhibitor used clinically to treat peripheral artery disease, on renal function and TIF. Studies were performed in sham-PUO rats and rats with 14-day PUO or 30-day PUO receiving vehicle in drinking water or PTF (400 mg/liter in drinking water). At day-14 PUO, glomerular filtration rate (GFR) was markedly and similarly depressed in rats receiving vehicle or PTF as compared with sham-operated rats. However, at day-30 PUO, GFR in rats receiving PTF was significantly higher than that in rats receiving vehicle, approaching the level seen in the sham-operated rats. At day-30 PUO, histologic studies also revealed a marked reduction of TIF in rats treated with PTF as compared with the rats receiving vehicle in drinking water. Western blot analysis demonstrated that at day-30 the expression of α-smooth muscle actin (an indicator of renal fibrosis) in the medulla was significantly reduced in PUO rats treated with PTF. In conclusion, PTF treatment ameliorated renal fibrosis and helped preserve renal function in a rodent model of PUO.

Effects of nicorandil on renal function and histopathology in rats with partial unilateral ureteral obstruction.

To evaluate the effects of nicorandil in a rat kidney model of partial unilateral ureteral obstruction (PUUO). Thirty male rats were randomly divided into three groups as follows: (1) Group 1 (Sham-control), ureters of the rats were manipulated but not ligated; (2) Group 2 (PUUO-untreated), PUUO was performed with two-thirds of the left ureter embedded in the psoas muscle; and (3) Group 3 (PUUO-nicorandil treated). After PUUO was established, nicorandil (15 mg/kg/day) was administered by gastric lavage for 21 days to determine its effects on PUUO-induced histopathological-, functional-, and oxidative stress-induced changes. The serum levels of blood urea nitrogen and creatinine were reduced in Group 3. The level of urinary albumin and the ratio of urinary protein/creatinine were increased in the kidneys of Group 2 but decreased in Group 3. Malondialdehyde value was decreased in Group 3 compared with Group 2. Antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase) were decreased in Group 2. Nicorandil treatment caused an increase in these enzyme activities. In Group 3, leukocyte infiltration and tubular dilatation were significantly reduced. Other parameters, such as degeneration of tubular epithelium and fibrosis, also showed a marked improvement in Group 3. Expression of inducible nitric oxide synthase in Group 2 and expression of endothelial nitric oxide synthase in Group 3 were significantly elevated. Nicorandil can inhibit renal tubular damage and tubulointerstitial fibrosis by reducing the effects of oxidative stress after PUUO.

Mechanisms of Increase in Renal Blood Flow During Partial Ureteral Obstruction in Dogs / 대한신장학회잡지

Although tubuloglomerular feedback (TGF) is involved in ureteral obstruction-induced increase in renal blood flow (RBF), its contribution to RBF is not well established due to the concommitant increases in prostaglandin (PG) and renal interstitial fluid pressure (Pisf), both of which affect RBF one way or the other. Since Pisf and TGF are closely affected by renal hemodynamics, RBF will respond differently to increases in ureteral pressure depending on renal hemodynamic conditions. Therefore, the purpose of the present study was to investigate how the changes in renal hemodynamics affect the response of RBF to increases in ureteral pressure. The effect of PG on RBF was assessed by comparing the effects obtained before and after indomethacin, a cyclooxygenase inhibitor. Six anesthetized dogs were prepared with flow probes and inflatable silastic occluder around the renal artery, the ureteral catheter with its free end attached to a water reservoir, and the arterial and venous catheters. RBFs were obtained at ureteral pressures of 0, 15, and 40cmH2O during the maintenance of the renal artery pressure (RAP) at the level of systemic arterial pressure, 10mmHg above and below the lower autoregulatory limit of RBF (65+/-4 mmHg) both before and after indomethacin administration (10mg/kg). In response to the ureteral pressure of 40cmH2O, RBF increased from 172+/-6 to 185+/-10ml/min when RAP's were equal to systemic arterial pressure and decreased from 162+/-10 to 120+/-9 ml/min when RAP's were 55+/-4mmHg. Indomethacin pretreatment, depending on the level of RAP either prevented an increase or augmented a decrease in RBF in response to ureteral pressure elevation. This suggests that RAP-dependent changes in susceptibility of the renal venous system to compression by increased Pisf is the main mechanism by which the changes in renal perfusion pressure modulate the response of RBF to ureteral pressure elevation.

Hydronephrotic atrophy after partial ureteral obstruction: Experimental model and natural history / 대한비뇨기과학회지

Partial ureteral obstruction was studied in male ICR mice in an attempt to observe the natural history of hydronephrotic atrophy. The left ureter was placed into the left psoas muscle, as descried by Ulm and Miller, to create a partial ureteral obstruction. In partial ureteral obstruction group, there was significant weight reduction of hydronephrotic kidney during the first two weeks. And then there was no further weight reduction. In complete ureteral obstruction group, there was progressive weight reduction and gain in hydronephrotic and contralateral kidney, respectively. These observations lead to conclusion that hydronephrotic atrophy after partial unilateral ureteral obstruction is not a progressive disease but develops in two phases: a destructive phase and a steady state phase.