Effects of 24-hour unilateral ureteral obstruction on glomerular hemodynamics in rat kidney.

Glomerular hemodynamics were studied, by micropuncture, in Munich-Wistar rats submitted to 24-hour unilateral ureteral ligation (UUL). Glomerular capillary pressure (PG), intratubular pressure (PT) and pressure in the first-order peritubular capillaries (EAP) were measured with a servonulling device. Single nephron filtration fraction (SNIFF) was calculated fmom arterial and peritubular blood protein concentration. SNGFR was both measured by conventional micropuncture techniques and calculated from efferent arteriole blood flow (EABF) and SNFF. Afferent arteriole blood flow (AABF) and resistance of afferent (Ra) and efferent (Re) arterioles were calculated. Measurements were repeated 1 to 2 hours after the release of the ureter. Sham-operated rats were used as control. UUL caused a marked increase in Ra (from 4.9 +/- [SD] 2.4 to 12.7 +/- 5.1 dynes/sec/cm-5). The fall in SNGFR (from 111.9 +/- [SD] 23.9 to 34.4 +/- 23.1 nl/min/kg body wt) was secondary to a decrease in both PG and AABF. A further increase in Ra (16.0 +/- 6.7 dynes.sec.cm-5) occurred after releasing the ureter. SNGFR, however, was unaltered (33.7 +/- 16.6 nl/min/kg body wt) since PG decreased parallel to PT, but AABF did not significantly change. Conclusion. Ureteral obstruction determines, in 24 hours, a marked cortical ischemia that is not promptly reversed by ureteral release.     

Effect of ureteral obstruction on proximal tubular functions of rat kidney

The effect of complete unilateral ureteral obstruction (CUUO) on proximal tubular functions was studied in rats, using the K+-sensitive microelectrode technique and split oil drop method. In the control kidneys peritubular membrane potential (EMperi) and intracellular potassium activity (aKi) were -70.8 +/- 7.0 mV and 81.2 +/- 22.0 mEq/liter (mean +/- SD), respectively. In the CUUO kidneys both EMperi and aKi were progressively reduced with the duration of obstruction. However, in all tubules aKi values were still above the electrochemical equilibrium. In the three days' CUUO kidneys EMperi and aKi were -51.5 +/- 11.7 mV and 53.8 +/- 22.8 mEq/liter, respectively. Rate of fluid absorption (JVL;nl./sec. mm.) across the proximal tubular epithelium from Ringer solution in the control and three days' CUUO kidneys was 0.029 and 0.0065 respectively. In the CUUO kidneys there were wide variations in JVL and EMperi, but there was a clear correlation between these two variables. JVL from choline chloride solution was negligible in both control and CUUO kidneys. From above results, it was suggested that the proximal tubular reabsorption primarily depending on the Na+-K+ pump might be reduced but still working in the CUUO kidney, and thus the proximal tubular reabsorption might take part in preservation of glomerular filtration during the obstruction.     

Effects of acute ureteral obstruction on glomerular hemodynamics in rat kidney

In order to study the effects of acute ureteral obstruction on glomerular hemodynamics, glomerular hydrostatic capillary pressure (PG), pressure in the first-order peritubular capillaries (EAP), and intratubular pressure (PT) were directly measured in superficial nephrons on Munich-Wistar rats by micropuncture with a servo-nulling device, in control conditions and one to two hours after ureteral ligation. Single nephron filtration fraction (SNFF) was calculated from arterial and peritubular blood protein concentration. SNGFR was measured by conventional micropuncture techniques in control conditions and was calculated from efferent arteriole blood flow (EABF) and SNFF during ureteral obstruction. EABF was obtained by timed complete collection of blood from superficial efferent arterioles. Afferent arteriole blood flow (AABF) and resistance of afferent (Ra) and efferent arterioles (Re) were calculated from conventional equations. Ureteral obstruction markedly increased PT from 12.9 +/- 1.4 to 36.8 +/- 6.1 (SD) mm Hg. The fall in SNGFR (from 23.3 +/- 6.4 to 17.9 +/- 5.2 [SD] nl/min) was blunted by the rise in PG (from 45.5 +/- 3.6 to 59.3 +/- 4.0 [SD] mm Hg) and AABF (from 130.0 +/- 59.1 to 144.2 +/- 69.0 [SD] nl/min), secondary to a fall in Ra. These results demonstrate that SNGFR is maintained early after complete ureteral obstruction because of afferent arteriole dilatation.     

罗格列酮对单侧输尿管梗阻大鼠肾脏的保护作用

目的观察罗格列酮对单侧输尿管梗阻(UUO)大鼠肾皮质过氧化物酶体增殖物活化受体(PPAR)γ、转化生长因子(TGF)β1表达介导的肾间质纤维化的作用。方法UUO大鼠给予罗格列酮5mg·kg-1·d-1灌胃,用免疫组化、RT-PCR及Western印迹的方法检测术后7d、14dPPARγ、TGF-β1、增殖细胞核抗原(PCNA)表达量及观察肾脏病理改变。结果与假手术组相比,UUO组及药物治疗组PPARγ、TGF-β1、、PCNA表达均增高且UUO组显著高于治疗组(P<0.05)。结论罗格列酮可通过活化PPARγ,下调TGF-β1,从而减轻UUO术后肾组织间质纤维化。     

螺内酯对单侧输尿管梗阻大鼠肾脏的保护作用

目的观察螺内酯对单侧输尿管梗阻(UUO)大鼠肾皮质金属蛋白酶1组织抑制剂(TIMP-1)介导的肾间质纤维化的影响。方法UUO大鼠给予螺内酯20mg·kg-1·d-1灌胃,用免疫组化及RT-PCR的方法检测术后7d、14d、21d的TIMP-1表达量并观察肾脏病理改变。结果与假手术组相比,UUO组及螺内酯组的TIMP-1mRNA和TIMP-1蛋白表达水平均明显增高(P<0.01),且UUO组显著高于螺内酯组(P<0.01)。结论螺内酯可通过下调TIMP-1减轻UUO术后肾组织间质纤维化。     

大黄酸对单侧输尿管梗阻大鼠肾脏的抗氧化保护作用

目的观察大黄酸（RH）对单侧输尿管梗阻（UUO）大鼠肾间质损伤的抗氧化保护作用。方法将30只雄性SD大鼠分成假手术组（Sham组）6只;UUO模型组（UUO组）和RH干预组（UUO＋RH组）各12只。除Sham组外,UUO组和UUO＋RH组分别在第3、7天测定大鼠左肾皮质匀浆中脂质过氧化物标志物丙二醛（MDA）及抗氧化酶过氧化氢酶（CAT）和超氧化物歧化酶（SOD）含量。结果UUO组较Sham组肾脏病理改变加重、肾组织MDA含量升高（P〈0.05）、SOD和CAT含量下降（P〈0.05）;UUO＋RH组较UUO组肾间质纤维化程度减轻、。肾组织MDA含量降低（P〈0.01）、SOD和CAT含量升高（P〈0.01）。结论RH能减少单侧输尿管梗阻侧肾皮质脂质过氧化物的产生,同时增加抗氧化酶的含量,通过改善UUO大鼠肾脏氧化应激来发挥肾脏保护作用。     

Successful 24-hour preservation of the ischemic canine kidney with Euro-Collins solution

The effect of 35 minutes of warm ischemia (37C) on renal function and adenine nucleotide content of canine kidneys preserved for 24 and 48 hours in Euro-Collins (EC) solution was investigated. In addition, the effect of donor pretreatment with intravenous mannitol, furosemide and methylprednisolone and the addition of adenosine triphosphate (ATP/MgCl2) to the EC flush and storage solution was studied. Donor pretreatment or the addition of ATP/MgCl2 to the flushing and storage solution did not significantly affect postautotransplant renal function of kidneys stored for 24 hours, although it improved tissue adenine nucleotide levels. Results after 48-hour preservation were significantly poorer. These experiments demonstrate that canine kidneys subjected to 35 minutes of warm ischemia time can be stored for 24 hours in EC solution and thereafter provide immediate life-sustaining function.     

Long-term effects of 24-hr unilateral ureteral obstruction on renal function in the rat

To characterize the pattern of recovery following release of unilateral ureteral obstruction of 24-hr duration, rats were studied with whole kidney clearance techniques, 3 hrs, 8, 14, and 60 days after release. The single nephron glomerular filtration rate (SNGFR) of superficial and juxtamedullary nephrons was estimated with a modification of Hanssen's technique in rats studied 8 and 60 days after ureteral release. The whole kidney glomerular filtration rates (GFR) were decreased markedly 3 hrs after relief of obstruction, but gradually increased and by 14 days, the GFR of the postobstructed kidney (POK) and the contralateral kidney (CK) were comparable. This recovery of GFR was not a consequence of a homogeneous improvement in SNGFR. At 8 days, more than 15% of superficial and juxtamedullary nephrons were not filtering in the POK. This decrease in the percent of filtering nephrons persisted to 60 days post release, indicating a permanent loss of nephron units. The SNGFR of the residual nephrons of the POK was significantly greater than that of the CK at 8 and 60 days following ureteral release. Thus, acute unilateral ureteral obstruction results in a permanent loss of filtering nephrons, which is offset by hyperfiltration of those remaining. Abnormalities in renal tubule function persisted beyond the time (14 days) when whole kidney GFR had returned to normal. These abnormalities were in distal tubule function. Urine osmolality was consistently lower at all time intervals post release, as was net acid excretion. The results of the present study suggest that these abnormalities are a consequence of the reduction in the number of filtering juxtamedullary nephrons and/or to abnormalities in collecting duct function.     

Effect of lisinopril on renal tissue damage in unilateral ureteral obstruction in rats

In this study, it was aimed to investigate apoptosis in renal injury and the effect of lisinopril in rat model, which constitute unilateral ureteral obstruction. The retroperitoneal ureter was ligated with a 4.0 silk for the experimental model of ureteral obstruction in Wistar albino rats. Untreated group (n = 20) received no treatment. For the lisinopril-treated group (n = 20), 20 mg/kg/day of drug was given orally. Ultrastructural differences were analyzed using electron microscopic technique; apoptotic distribution was analyzed using the TUNEL method. After electron microscopic evaluation, on the 4th and 14th day in the untreated group, edema in the glomeruli, loss of microvillus and apoptotic cells in proximal tubule cells and sclerosis in the glomeruli were detected. On the 4th day in the lisinopril-treated group, the kidney was ultrastructurally normal and a less number of apoptotic cells were only observed on the 14th day. On light microscopic examination on the 4th and 14th day in the untreated group, while the glomeruli were normal in structure, the boundary of the proximal tubule was disrupted and some picnotic cells in both the proximal and collecting tubules were observed. In both 4th and 14th day of the lisinopril-treated group, kidney showed normal structure, although in some places picnotic cells in the collecting tubules were observed. In conclusion, lisinopril was effective and it may prevent early renal damage in the direct obstruction model.     

Late ureteral obstruction after kidney transplantation

Abstract Today, the incidence of urological complications following renal transplantation is 2 %-10 %. Most of these complications occur within the 1st year and affect the distal ureter. We report on two patients who developed very late ureteral obstruction, 14 and 18 years after transplantation. Both patients had rejection episodes 1 and 10 months prior to the ureteral stenosis. Histological examination of one resected ureter revealed findings strongly suggestive of a rejection process. Open surgery with antirefluxive reimplantation into the bladder was successful in both patients, with a postoperative observation time of 20 and 8 months, respectively. We conclude that a percutaneous nephrostomy may be required in patients with rising creatinine and incipient hydronephrosis even long after transplantation has been performed.     

Late ureteral obstruction after kidney transplantation

Today, the incidence of urological complications following renal transplantation is 2%–10%. Most of these complications occur within the 1st year and affect the distal ureter. We report on two patients who developed very late ureteral obstruction, 14 and 18 years after transplantation. Both patients had rejection episodes 1 and 10 months prior to the ureteral stenosis. Histological examination of one resected ureter revealed findings strongly suggestive of a rejection process. Open surgery with antirefluxive reimplantation into the bladder was successful in both patients, with a postoperative observation time of 20 and 8 months, respectively. We conclude that a percutaneous nephrostomy may be required in patients with rising creatinine and incipient hydronephrosis even long after transplantation has been performed.     

Calcium channel blocker nisoldipine limits ischemic damage in rat kidney

The effects of the calcium channel blocker nisoldipine on renal function after 60 min. normothermic ischemia and contralateral nephrectomy were studied in male Wistar rats. Nisoldipine (300 ppm) was given in a standard diet as well as one hour prior to ischemia (10 mg./kg. orally). Survival, serum urea, serum creatinine, urine volume and creatinine clearance were used to test the effectiveness of the drug. Nisoldipine treatment resulted in the survival of all animals (compared to 66.6 per cent in the untreated group) and improved immediate and long term (14 days) renal function. The drug given post ischemia only was not effective, suggesting that nisoldipine must be present in the kidney during ischemia. The beneficial effects of the drug in postischemic acute renal failure may be attributed in part to effects on postischemic renal hemodynamics. Additional direct effects on ischemic renal epithelial cells, presumably by inhibiting transmembrane calcium fluxes, cannot be excluded.     

大鼠输尿管部分梗阻后平滑肌形态及功能改变

目的 探讨单侧输尿管部分梗阻后输尿管平滑肌超微结构、收缩功能和自律性的改变.方法 Wistar大鼠80只.随机分4组:8周实验组、8周对照组、16周实验组、16周对照组.每组20只.实验组大鼠左侧输尿管上1/2段腰大肌包埋造成单侧输尿管部分梗阻的动物模型,对照组仅分离左侧输尿管.成模后于不同实验点分离大鼠输尿管进行离体肌条实验,测定肌条的收缩幅度和频率的改变,并通过透射电镜观察梗阻后平滑肌超微结构的变化.结果 8周实验组输尿管收缩力和收缩频率分别为(0.62±0.38)g、(18.52±6.70)次/min,8周对照组分别为(0.38±0.36)g、(14.80±4.98)次/min,2组比较差异均有统计学意义(P＜0.05).16 周实验组输尿管收缩力和收缩频率分别为(0.15±0.10)g、(12.84±3.32)次/min,16周对照组分别为(0.41±0.38)g、(16.48±3.44)次/min.2组间比较差异均有统计学意义(P＜0.05).8周实验组均高于16周实验组(P＜0.05),8周对照组与16周对照组比较差异无统计学意义(P＞0.05).透射电镜观察到8周实验组平滑肌细胞胞质中线粒体数增多,而16周实验组平滑肌细胞胞质中线粒体数目减少、线粒体肿胀和空泡化、细胞间质中可见大量胶原纤维增生.结论 输尿管梗阻8周的大鼠输尿管肌条自律性和收缩力增加,输尿管平滑肌细胞胞质中线粒体增多,可能是机体代偿所致.输尿管梗阻16周后输尿管平滑肌自律性和收缩力均降低.平滑肌细胞胞质中线粒体数目减少,线粒体肿胀和空泡化,细胞间质中有大量胶原纤维增生,呈失代偿表现.     

Heme oxygenase-1 protects rat kidney from ureteral obstruction via an antiapoptotic pathway

This study examined the functional significance of heme oxygenase-1 (HO-1) expression on renal injury induced by ureteral obstruction in the rat kidney. Male Sprague-Dawley rats were divided into three groups, after which unilateral ureteral obstruction (UUO) was performed: untreated (group 1), treated with 30 mg/kg body wt hemin (group 2), and treated with 50 microg/kg body wt zinc (alpha) protoporphyrin eta (ZnPP) and 30 mg/kg hemin (group 3). After 7 and 14 d, histologic changes and the expression of HO-1, Bcl-2, Bad, TGF-beta, and cleaved caspase-3 were examined. Tubular lumens were dilated and epithelial cells were flattened on day 7 after UUO. Interstitial fibrosis and separation of the tubules were markedly increased on day 14. In contrast, the kidneys that were treated with hemin exhibited minimal interstitial fibrosis and flattening of epithelial cells on day 7 and fewer changes on day 14 than in the controls. However, treatment with ZnPP, an inhibitor of HO enzyme activity, eliminated the beneficial effect of hemin on interstitial fibrosis and tubular dilation. Increased HO-1 expression was associated with increased Bcl-2. In the ZnPP-treated rats, Bcl-2 signals were decreased compared with the hemin group. The level of proapoptotic Bad was not changed in any group. The positive cells for cleaved caspase-3 were significantly increased in renal tubular epithelial cells and tubulointerstitial cells in the obstructed rats, and hemin treatment decreased the caspase-3 activation. This study demonstrates that upregulation of HO-1 provides protection against renal injury that follows UUO. This effect is dependent on modulation of the antiapoptotic pathway by HO-1 expression.