阻塞性黄疸大鼠肾脏自分泌内皮素的变化及其与肾功能损害的关系

目的　探讨阻塞性黄疸时肾脏自分泌内皮素 (ET)的变化及其与肾功能损害的关系。方法　结扎胆总管(BDL)制备阻塞性黄疸大鼠模型 ,作为实验组 ,对照组鼠仅行假手术。分别于术后 5、1 0及 1 5d ,两组各取 1 0只大鼠检测其肾脏对氨基马尿酸清除率 (CPAH)、菊粉清除率 (CIN)和钠排泄分数 (FENa+) ,并用鲎试剂法测定血浆内毒素 (EX)水平 ,放射免疫法测定肾动、静脉血浆及肾组织中ET 1含量。结果　①实验组术后 5d仅FENa+明显高于对照组 (P<0 .0 1 ) ,术后 1 0d起 ,CPAH、CIN及FENa+呈进行性下降 ,术后 1 5dFENa+已较对照组低 ,与对照组比较差异有显著性 (P<0 .0 1 ) ;②实验组术后血浆EX水平呈进行性升高 ,与对照组比较差异有显著性 (P<0 .0 1 ) ;③实验组术后肾动脉血浆ET 1水平呈持续性降低 ,而肾静脉血浆及肾组织中ET 1含量呈持续性升高 ,与对照组比较差异有显著性 (P<0 .0 1 ) ;④血浆EX水平与肾组织ET 1含量呈正相关 (r =0 .762 4 ,P<0 .0 1 ) ,肾组织ET 1含量与CPAH和CIN呈负相关 (r=- 0 .883 2 ,P<0 .0 1 ;r =- 0 .945 2 ,P<0 .0 1 )、与FENa+呈正相关 (r=0 .873 4 ,P<0 .0 1 )。结论　内毒素血症及其诱导的肾内ET分泌增加在阻塞性黄疸所致大鼠肾损害中可能具有重要作用     

舒胆合剂防治阻塞性黄疸肾功能障碍的作用机制

目的 探讨在阻塞性黄疸(OJ)时舒胆合剂的抗内毒素及对肾功能的保护作用。方法 SD大鼠胆总管结扎后分3组，每组10只，分别用2mL舒胆合剂、乳果糖液(每100mL含乳果糖67g)、生理盐水灌胃，连用9d。假手术组10只，用2mL生理盐水灌胃。观察内毒素、血和肾组织中内皮素(ET)、一氧化氮(NO)的含量、一氧化氮合酶(NOS)活性及肾功能的变化。结果 舒胆合剂组与乳果糖组血内毒素、血和肾组织ET水平较生理盐水组明显降低，血和肾组织N0、NOS活性、内生肌酐清除率、肾皮质血流量较生理盐水组明显升高。结论 在OJ时，中药舒胆合剂有抗内毒素作用，并通过减少体内内毒素水平来降低体内ET水平，升高N0水平起到保护肾功能的作用。     

内毒素引起阻塞性黄疸大鼠肾功能障碍的机制

目的 探讨阻塞性黄疸(obstructive jaundice,OJ)时内毒素引起肾功能障碍的机制.方法 SD大鼠60只,胆总管结扎后,分5 d(B1),10 d(B2),15 d(B3)三组,每组各10只,同时建立相应对照组(A1,A2,A3),另30只胆总管结扎后分3组(SHUD,LAC,NS),每组各10只,分别用2 ml舒胆合剂、乳果糖液、生理盐水灌胃,连用9 d.观察内毒素、血和肾组织中内皮素(endothelin,ET)、一氧化氮(nitric oxide,NO)的含量、一氧化氮合酶(nitric oxide synthase,NOS)活性及肝、肾功能的变化.结果 血内毒素与血、肾组织ET含量,ET/NO比值呈显著正相关(P＜0.05,r=0.630,0.438,0.496,0.453),与肌肝清除率(creatinine clearance,Ccr)和肾皮质血流量(renal cortical blood flow,BCBF)呈显著负相关(P＜0.05,r=-0.600,-0.410).血、肾组织ET/NO比值与Ccr,RCBF呈显著负相关(P＜0.05,r=-0.449,-0.558,-0.626,-0.731).血和肾组织内NO水平与内毒素水平呈负相关(P＜0.05,r=-0.518,-0.441),与Ccr、RCBF呈正相关(P＜0.05,r=0.422,0.496,0.400,0.659).SHUD组与LAC血内毒素、ET水平组明显降低,血和肾组织NO,NOS活性以及Ccr,RCBF较NS组明显升高.结论 OJ时内毒素可通过刺激ET的释放,提高ET/NO比值,使肾内缩血管因子与扩血管因子比例失调而损伤肾功能.     

喂饲左旋精氨酸对烫伤大鼠肠道保护作用机制的研究

目的探讨喂饲左旋精氨酸(L-Arg)对烫伤大鼠肠道缺血再灌注损伤的作用机制。方法将66只SD大鼠随机分为正常对照组(6只,不作烫伤和其他处理)、精氨酸组(30只,烫伤后2h喂饲70g/LL-Arg,1ml/次,2次/d)和普通喂养组(30只,烫伤后喂饲等量凉开水)。检测正常对照组及两组烫伤大鼠伤后6、12、24、48、72h肠组织内皮素(ET)水平、一氧化氮(NO)含量、ET/NO比值以及血浆内毒素水平的变化,并取回肠组织标本作病理学观察。结果伤后6、12、24h,精氨酸组大鼠肠组织ET水平分别为(0.80±0.26)、(0.75±0.30)、(0.63±0.22)ng/g,低于普通喂养组(1.26±0.38)、(1.34±0.37)、(0.97±0.19)ng/g(P<0.05);其NO含量显著高于普通喂养组(P<0.01);ET/NO比值和血浆内毒素水平均低于普通喂养组(P<0.05或0.01)。病理学观察显示,精氨酸组大鼠肠黏膜损伤情况明显轻于普通喂养组。结论喂饲L-Arg可减轻烫伤大鼠肠组织缺血再灌注损伤,有利于保护肠黏膜屏障功能。其机制为喂饲L-Arg后增加了肠黏膜局部NO的含量,有助于维持ET/NO比值的稳定。     

内毒素休克大鼠核因子κB活化规律及其在生物蝶呤诱生中的作用

目的观察内毒素休克大鼠血浆及主要脏器核因子(NF)κB活化规律及其对生物蝶呤(BH4)和一氧化氮(NO)表达水平的影响,探讨内毒素休克时NF-κB信号通路对BH4诱生NO的分子调控机制及其与多器官功能损害的关系。方法将47只大鼠按表格随机法分为正常组(8只)、内毒素／脂多糖(LPS)组(24只,每观察时相点8只,均同时注射LPS制成休克模型)和拮抗组[15只,每观察时相点5只,均同时注射LPS并以吡咯烷二硫代氨基甲酸盐(PDTC)拮抗]。休克及拮抗组于注射LPS后2、6、12 h观察,并与正常组同法处死,无菌留取大鼠血标本及肝、肺、肾组织,测定组织中NF-κB活性和三磷酸鸟苷环水解酶Ⅰ(GTP-CHⅠ)和诱导型一氧化氮合酶(iNOS)mRNA表达水平、血浆和组织中的BH4含量及NO水平、肝脏和肾脏功能指标、肺组织髓过氧化物酶活性。结果与正常组(例如肺组织中NF-κB活性为26±6)比较,LPS组大鼠组织中NF-κB迅速活化(P<0．01),并于注射后2 h达峰值(肺组织中为291±44);LPS组各组织中GTP-CHⅠ和iNOS mRNA表达、BH4和NO水平也较正常组明显升高(P<0．05或0．01),至伤后12 h仍持续较高水平。此外,该组相应器官功能均受到不同程度的损害。应用PDTC的拮抗组大鼠各组织中NF-κB活性均较LPS组有所降低,GTP-CHⅠ、iNOS mRNA表达及BH4、NO水平显著受抑,肝、肺、肾功能明显改善。结论内毒素休克时机体内NF-κB通路高度活化,并对BH4／NO系统具有明显调节效应;可通过下调BH4介导的iNOS的过度活化抑制NF-κB信号途径,从而减轻组织炎性反应,对机体脏器功能起到保护作用。     

内皮素、一氧化氮与阻塞性黄疸肾功能障碍关系的实验研究

目的 研究内皮素(Endothelin ET)、一氧化氮(Nitric Oxide NO)与阻塞性黄疸(Obstructive Jaundice OJ)肾功能障碍的关系。方法 雄性SD大鼠胆总管结扎后随机分成5天、10天、15天三组，同时建立对应的假手术对照组。观察肾功能的变化，同时测定血和肾组织ET、NO水平及一氧化氮合酶(Nitric Oxide Synthetase NOS)活性，并用图像分析检测ET—1mRNA和NOS—mRNA表达的部位和量的变化。结果 随胆总管梗阻时间的延长，血和肾组织ET升高，NO下降，ET／NO比值与内生肌酐清除率(Creatinine clearance rate Ccr)、肾皮质血流(Renal cortex blood flow RCBF)呈负相关。肾组织ET—1mRNA和iNOS mRNA表达增加，血和肾组织NOS活性降低。结论 血和肾组织ET升高，NO下降，ET／NO比值升高是导致OJ时肾功能损伤的原因之一。     

氨基胍对内毒素休克大鼠肝损伤的保护作用研究

目的 探讨诱导型一氧化氮合酶(iNOS)抑制剂氨基胍对内毒素休克大鼠肝脏的组织学和超微结构的影响。方法 取雄性wistar大鼠24只．随机分为正常对照组、内毒素对照组和氨基胍治疗组．每组各8只。用大肠杆菌内毒素(LPS)复制大鼠内毒素性休克模型．氨基胍治疗组采用氨基胍治疗。观察并比较三组大鼠肝脏的组织学、超微结构及其血浆一氧化氮(NO)含量的变化。结果 光镜下可见．内毒素组肝组织有散在小脓肿灶形成．肝细胞坏死,中性白细胞浸润．而氨基胍治疗组的肝组织受损程度较轻。电镜下可见,内毒素组的肝细胞核出现融解性空斑．线粒体肿胀和线粒体嵴数量减少．而氨基胍则对肝脏的结构起到一定的保护作用。内毒素对照组血浆NO水平明显高于正常对照组．给予氨基胍治疗后血浆NO水平明显下降．但仍高于正常对照组。结论 氨基胍通过选择性抑制iNOS活性．抑制了大鼠内毒素休克时过量的NO的产生．保护了肝脏的功能．具有潜在的临床应用价值．值得更深入地研究。     

栀子提取液治疗大鼠重症急性胰腺炎的实验研究

目的　 观察栀子提取液对大鼠重症急性胰腺炎 (SAP)的治疗作用。 方法　 经胆胰管逆行注射 1 5 %去氧胆酸钠建立SAP模型 ,用栀子提取液和临床常用药善宁进行对比治疗 ,观察血中淀粉酶 (AMY)、内毒素 (ET)、一氧化氮 (NO)、过氧化脂质 (LPO)以及胰腺组织LPO的变化 ,并对胰腺组织进行病理学检查。 结果 　模型组血中AMY、NO、ET、LPO以及胰腺组织LPO明显升高 (P <0 0 5 ) ,光镜下胰腺组织病理损害明显。栀子提取液和善宁治疗后 ,上述各指标均较模型组明显改善 (P <0 0 5 )。 结论　 栀子提取液可以减轻氧自由基、NO、ET的损伤 ,对SAP具有一定的治疗作用。     

黄芪对失血性休克再灌注大鼠小肠粘膜iNOS和ET蛋白表达的影响

目的观察大鼠失血性休克再灌注后诱导型一氧化氮合酶(iNOS)和内皮素(ET)在小肠粘膜的表达及黄芪对它们的影响。方法雄性SD大鼠24只,随机分成对照组、模型组和黄芪组。复制重度失血性休克及复苏动物模型,黄芪于再灌注前静脉注入,造模完成后观察各组动物小肠粘膜病理学变化,用免疫组化法检测肠粘膜组织诱导型iNOS和ET表达。结果模型组肠粘膜损伤最重,黄芪具有保护缺血-再灌注肠粘膜的作用,对照组肠粘膜无损伤;Chiu’s评分模型组最大,黄芪组次之,对照组最低(P<0·01)。各组肠粘膜均可见到iNOS和ET表达。模型组iNOS表达明显增强,表达的灰度值明显高于其它两组(P<0·05);黄芪组比对照组有增高趋势,但两组间表达的灰度值无显著性差异。模型组和黄芪组ET表达灰度评分值高于对照组(P<0·05),与模型组相比,黄芪组肠粘膜ET表达灰度值虽有所降低,但无显著性差异。结论黄芪能减少失血性休克再灌注小肠粘膜组织iNOS表达,这可能与其抗失血性休克再灌注肠粘膜的损伤机制有关。     

细胞外信号调节激酶在内毒素休克大鼠生物喋呤诱生中的作用机制探讨

目的观察细胞外信号调节激酶（ERK）通路抑制剂对生物喋呤（BH4）和一氧化氮（NO）表达及核因子-kB（NF-kB）活化的影响,探讨内毒素休克时ERK信号通路与NF-kB的交汇作用及其对BH4诱生NO的调控机制。方法采用内毒素休克模型,60只大鼠随机分为正常对照组（n=8）、内毒素休克组（n=32）和ERK抑制剂PD98059拮抗组（n=20）。留取动物肝、肺、肾组织进行NF-kB活性分析以及三磷酸鸟苷环水解酶I（GTP—CHⅠ）、诱生型一氧化氮合酶（iNOS）基因表达的检测,并测定组织及血浆中BH4、NO水平。结果内毒素攻击可导致动物肝、肺、肾组织GTP-CHⅠ基因表达和BH4水平明显升高,至伤后24h仍持续于较高水平;与之相应,组织iNOS基因表达和NO水平亦明显升高;各组织NF-kB迅速活化,并于2h达峰值。采用PD98059处理后,内毒素休克动物肾组织GTP—CHⅠ mRNA表达明显受抑,肝、肺组织GTP—CHⅠmRNA表达仅呈现降低趋势;血浆及肝、肾组织中BH4水平12h显著降低;同样,各组织iNOS mRNA表达及NO水平早期亦显著降低。此外,PD98059处理组动物肝组织2～6h、肺组织2h、24h和肾组织24h时相点NF-KB活性显著降低。结论内毒素休克时抑制ERK通路,能部分下调BH4和NO表达与NF-kB的活化,表明ERK与NF-kB通路间可能存在交汇作用,共同参与了BH4诱生NO的调控作用。     

Endotoxemic renal failure in mice: Role of tumor necrosis factor independent of inducible nitric oxide synthase

BACKGROUND: Renal failure is a frequent complication of sepsis with a high mortality. Tumor necrosis factor (TNF) has been suggested to be a factor in the acute renal failure in sepsis or endotoxemia. Recent studies also suggest involvement of nitric oxide (NO), generated by inducible NO synthase (iNOS), in the pathogenesis of endotoxin-induced renal failure. The present study tested the hypothesis that the role of TNF in endotoxic renal failure is mediated by iNOS-derived NO. METHODS: Renal function was evaluated in endotoxemic [Escherichia coli lipopolysaccharide (LPS), 5 mg/kg IP] wild-type and iNOS knockout mice. The effect of TNF neutralization on renal function during endotoxemia in mice was assessed by a TNF-soluble receptor (TNFsRp55). RESULTS: An injection of LPS to wild-type mice resulted in a 70% decrease in glomerular filtration rate (GFR) and in a 40% reduction in renal plasma flow (RPF) 16 hours after the injection. The results occurred independent of hypotension, morphological changes, apoptosis, and leukocyte accumulation. In mice pretreated with TNFsRp55, only a 30% decrease in GFR without a significant change in RPF in response to LPS, as compared with vehicle-treated mice, was observed. Also, the serum NO concentration was significantly lower in endotoxemic wild-type mice pretreated with TNFsRp55, as compared with untreated endotoxemic wild-type mice (260 +/- 52 vs. 673 +/- 112 micromol/L, P < 0.01). In LPS-injected iNOS knockout mice and wild-type mice treated with a selective iNOS inhibitor, 1400W, the development of renal failure was similar to that in wild-type mice. As in wild-type mice, TNFsRp55 significantly attenuated the decrease in GFR (a 33% decline, as compared with 75% without TNFsRp55) without a significant change in RPF in iNOS knockout mice given LPS. CONCLUSIONS: These results demonstrate a role of TNF in the early renal dysfunction (16 h) in a septic mouse model independent of iNOS, hypotension, apoptosis, leukocyte accumulation, and morphological alterations, thus suggesting renal hypoperfusion secondary to an imbalance between, as yet to be defined, renal vasoconstrictors and vasodilators.     

Renal function and functional reserve in healthy elderly individuals

BACKGROUND: Aging is characterized by a decline in renal function and by a susceptibility to renal diseases. However it is not clear whether the observed changes are solely hemodynamic, structural or both. We evaluated renal function, functional reserve (RFR) and morphology in healthy elderly individuals. METHODS: Healthy participants (n=19) were divided into young (n=6, age range 25-37 years), middle-aged (n=6, 44-74 years) and elderly (n=7, 81-96 years). Nitric oxide (NO), plasma renin activity (PRA) and aldosterone, renal plasma flow (RPF) by p-aminohippurate clearance (CPAH) and glomerular filtration rate (GFR) by inulin clearance (CIN) were determined before and during maximal vasodilating stimuli, induced with the infusion of dopamine and amino acids. Glomerular sclerosis, lumen area and wall thickness of afferent arterioles were determined by kidney biopsy from 36 healthy kidney donors and from 6 nephrectomies for renal carcinoma. RESULTS: GFR and RPF were slightly reduced in elderly individuals whereas filtration fraction (FF) was increased. GFR and RPF did not increase in the elderly after maximal vasodilating stimuli as in young and middle-aged subjects suggesting a reduction of RFR. NO, increased at baseline, did not increase further after vasodilating stimuli; while on the contrary, PRA, similar in the 3 groups at baseline, was not reduced by vasodilating stimuli in the elderly. Sclerotic glomeruli but not glomerular volume were significantly increased by aging. Afferent arteriole lumens were reduced by aging whereas wall thickness was unchanged. CONCLUSIONS: Renal function is preserved with aging in healthy subjects at the expense of a complete reduction of RFR. RFR may be wasted to compensate for the increased number of sclerotic glomeruli. Vascular changes, suggested by reduced arteriolar lumen, may be so advanced that even in the presence of high levels of vasodilatory molecules, kidneys are not responsive anymore to maximal vasoactive stimuli.     

Renal hemodynamic effects of L-arginine and sodium nitroprusside in heart transplant recipients

BACKGROUND: Long-term treatment with cyclosporine A (CsA) induces vasoconstriction in the kidney and causes renal impairment. An altered L-arginine (L-Arg)/nitric oxide (NO) pathway may play a key role in CsA nephrotoxicity. METHODS: We studied the effect of L-Arg (dosage, 17 mg/kg/min over 30 min), the precursor of NO synthesis, and sodium nitroprusside (SNP; dosage, 1.0 microgram/kg/min over 30 min) on renal hemodynamics in a double-blind, placebo-controlled, randomized, three-way cross-over study comprising 12 stable cardiac transplant recipients on long-term CsA treatment, 10 patients with chronic nephropathy not receiving CsA, and 13 healthy controls. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured by paraaminohippurate (PAH) and the inulin clearance method, respectively. RESULTS: In healthy subjects, L-Arg induced an increase in RPF (P = 0.009) and GFR (P = 0.001). By contrast, L-Arg did not induce renal hemodynamic effects in heart transplant patients or patients with chronic nephropathy. SNP reduced RPF (P = 0.050) and GFR (P = 0.005) in patients with chronic nephropathy but did not affect renal hemodynamics in heart transplant recipients or in healthy subjects. CONCLUSIONS: These data indicate that L-Arg cannot be used to reverse CsA-induced renal vasoconstriction in heart transplant recipients under long-term CsA treatment, although these patients have a normal renal response to SNP.     

Renal effects of low to moderate doses of dopamine in newborn piglets.

PURPOSE: Administration of dopamine to adult animal and human subjects results in increased renal blood flow, and it may also enhance the glomerular filtration rate. However, renal hemodynamic effects of exogenous dopamine in the neonate are unclear. In this study, we examined the renal actions of low to moderate doses of exogenous dopamine in newborn piglets. METHODS: The animals were anesthetized, catheterized for vascular access and urine collection, and assigned randomly to a control group or treatment groups receiving dopamine infusion at 2, 5, or 10 microg/kg/min. Data were collected at baseline, during dopamine infusion, and 1 hour after cessation of infusion. Mean arterial blood pressure (MAP) and heart rate (HR) were monitored. Glomerular filtration rate (GFR), cardiac index (CI), and renal blood flow (RBF) were determined. Fractional excretion of sodium (FENa) was calculated. RESULTS: Dopamine did not alter renal blood flow nor did it significantly alter CI in spite of a modest increase in heart rate and mean arterial blood pressure. There was a statistically significant increase in GFR at 10 microg/kg/min and in FENa at all doses. CONCLUSIONS: Low doses of dopamine produce significant natriuresis probably by direct action on renal tubules and at moderate doses via, both, increase in GFR and a direct tubular effect. Low and moderate doses of dopamine do not increase RBF as seen in adult animals, possibly because of immaturity of dopaminergic receptors in newborn piglets.     

Renal hemodynamic response to maximal vasodilating stimulus in healthy older subjects

BACKGROUND: It is still unclear whether age per se is associated with preservation of renal functional reserve, that is, of the increase in glomerular filtration rate (GFR) induced by appropriate vasodilating stimulus. METHODS: To gain insights into this issue, we evaluated the renal response to a maximal vasodilating stimulus, represented by the combined infusion of mixed amino acid solution (AA) and dopamine at renal dose (D), in 10 young subjects (median age of 30 years, range of 19 to 32) and in 11 subjects of older age (median age of 67 years, range of 65 to 76). Two further age-matched groups of young (N = 15) and older (N = 11) living kidney donors underwent renal needle biopsy immediately before nephrectomy to perform semiquantitative scoring (0 to 3) of arteriosclerosis in intrarenal arteries. All of the study subjects were nonsmokers with healthy status proven by extensive diagnostic evaluation excluding any risk factor of renal dysfunction. RESULTS: Basal renal plasma flow (RPF) and GFR were proportionally lower in older subjects (RPF, 361 +/- 29 vs. 618 +/- 34 mL/min/1.73 m(2), P < 0.001; GFR, 79 +/- 4 vs. 127 +/- 5.8 mL/min/1.73 m(2), P < 0.001). After AA + D, a significant increase of RPF and GFR was observed in both groups, but the older subjects exhibited a smaller percentage increment (RPF, 25.5 +/- 4.8 vs. 42.4 +/- 5.8, P < 0.05; GFR, 19.6 +/- 5.7 vs. + 33.8 +/- 6.4, P < 0.05). Furthermore, the maximal vasodilating stimulus was not able to restore renal hemodynamics in older subjects to the level measured in young controls at baseline. Renal vascular resistances were higher (P < 0.05) in the older subjects both at baseline (0.19 +/- 0.02 vs. 0.09 +/- 0.004 mm Hg/mL/min) and after AA + D (0.14 +/- 0.01 vs. 0.06 +/- 0.004). Light microscopy examination detected the presence of a greater degree of arteriosclerosis at the level of interlobular and arcuate arteries (0.89 +/- 0.15 vs. 0.45 +/- 0.08) and interstitial fibrosis/tubular atrophy (1.18 +/- 0.13 vs. 0.53 +/- 0.13) in older than in young subjects. CONCLUSIONS: Therefore, aging has adverse effects on renal function despite the absence of any risk factor for renal disease, including chronic smoking: (1) GFR and RPF are lower, and (2) the renal response to maximal vasodilating stimulus is impaired. These aging-related alterations of renal hemodynamics are possibly due to organic lesions in renal vasculature.     

Ischemic acute renal failure in the rat: effects of L-arginine and superoxide dismutase on renal function

BACKGROUND: Regulation of renal hemodynamics -- especially intraglomerular hemodynamics -- is closely related to the L-arginine (L-Arg)/nitric oxide (NO) pathway, both under basal conditions and in acute renal failure (ARF). Also, superoxide anions -- which may react with NO -- play a role in ischemic ARF. L-Arg not only has beneficial effects on glomerular filtration rate (GFR) but also reduces O2(-) production and prevents NO synthase isoform I up-regulation. Thus, it is of interest to elucidate whether the potential beneficial effects of L-Arg in reperfusion can be augmented by additional treatment with superoxide dismutase (SOD). METHODS: ARF was induced by renal artery clamping for 40 minutes. Animals were treated with either L-Arg, SOD, a combination of both, or saline. GFR, renal plasma flow (RPF), filtration fraction (FF) and blood pressure were recorded at baseline, after induction of ARF, during drug infusion and thereafter. RESULTS: Renal artery clamping induces a severe drop of GFR, RPF and FF, which all are improved by L-Arg and SOD. Increasing GFR is mainly due to better renal perfusion. FF fell after reperfusion and increased with L-Arg and SOD, indicating improvement of disturbed intrarenal hemodynamics. Combined administration of L-Arg and SOD showed similar effects in comparison with each substance alone, but did not induce additional effects on GFR and RPF. CONCLUSIONS: L-Arg and SOD exert beneficial effects in ischemic ARF. Probably, improvements in reducing NO availability and in enhancing O2(-) formation are both playing a mediating role. The underlying mechanisms regulating the interplay between NO availability and O2(-) formation need to be elucidated in further studies using -- aside from other means -- selective NOS inhibitors, intervention in different experimental phases and treatment for a longer period.     

Effects of acute reduction in blood pressure on the renal function of rats with diseased kidneys

We studied the effect of an acute reduction in blood pressure, induced by diltiazem, on the renal hemodynamics of spontaneously hypertensive rats (SHR) with focal glomerular sclerosis, as induced by adriamycin (ADR). Renal plasma flow (RPF) and glomerular filtration rate (GRF) were determined before (first period) and during (second period) intravenous infusion of diltiazem in SHR 4-6 weeks after ADR treatment (group 1), 14-20 weeks after treatment (group 2), and in controls without treatment (group 3). Rats in group 1 had a normal renal function (RPF and GFR) in the first period, which was not significantly different from control rats (group 3). Rats in group 2 showed a reduced renal function, reflected by the lower levels of RPF and GFR, compared with groups 1 and 3. Mean blood pressure decreased equally in the 3 groups by about 50 mm Hg after the infusion of diltiazem. During the second period, 13.4 or 12.4% increase in RPF and a 29.0 or 23.2% elevation of GFR were evident in groups 1 or 3, respectively. In contrast, a 32.0% reduction of RPF was observed in group 2, accompanied by a 25.7% decline of GFR. A reduction in renal function (percent change of RPF or GFR) significantly correlated with the severity of renal dysfunction (RPF or GFR in the first period) in group 2. Thus, the renal function of rats with diseased kidneys is sensitive to an acute reduction in blood pressure by diltiazem, and the sensitivity depends on the degree of renal deterioration.     

Acute Effects of Furosemide and Mannitol on Renal Function in the Early Postoperative Period

The effects of furosemide and mannitol on renal function in the immediate postoperative period were studied in 16 patients, who had undergone upper abdominal surgery under neurolept anaesthesia. Renal function was studied preoperatively and during the first postoperative hour with a standard clearance technique. The patients were then randomly given furosemide, 1 mg/kg b.w., or mannitol, 0.5 g/kg b.w. Renal function was further investigated during the following 6 h in periods of varying duration. The injection of furosemide caused an initial increase of renal plasma flow (RPF), while glomerular filtration rate (GFR) decreased. Striking increases of urine flow, fractional sodium, fractional chloride and fractional osmolal excretion were found. These increases reached maximum levels during the second 20-min clearance period after the injection. Fractional free water reabsorption decreased and during the first 20-min clearance period it changed into free water clearance. These changes had reached or nearly reached the preoperative control levels after 6 h.
The infusion of mannitol caused an initial rise in RPF, while GFR remained stable. Increases were found in urine flow, fractional sodium, fractional chloride, fractional osmolal excretions and fractional free water reabsorption. The changes reached maximum levels during the first 20-min control period and then gradually returned to the preoperative control levels.
Mannitol did not impair GFR and had a milder effect on renal function than furosemide. The losses of sodium and water were much smaller in the mannitol group than in the furosemide group. It is therefore concluded that mannitol should be used as the diuretic of choice in the treatment of postoperative oliguria in patients without known cardiovascular disease associated with increased preload and/or left ventricular insufficiency.     

Acute effects of ciclosporin on renal hemodynamics and urinary protein excretion in patients with the nephrotic syndrome.

The possibility that the renal hemodynamic abnormalities associated with ciclosporin (CS) administration are enhanced in nephrotic patients (NP), leading to severe impairment of renal function and/or to modifications in proteinuria, has not hitherto been tested. Ten NP and 8 healthy subjects (NC) were examined before and after oral CS administration (10 mg/kg body weight in NP and 12 mg/kg body weight in NC: a lower dosage was adopted in NP because of edema overestimating the actual body weight) under water diuresis by standard renal clearance methods. Basal blood volume was lower in NP. Blood CS levels were not significantly different in the two groups. Basal glomerular filtration rate (GFR) was similar in NP and NC, while renal plasma flow (RPF) was lower in NP. After CS, both GFR and RPF significantly decreased in the two groups, but the percent decrease in inulin clearance was greater in NP. Filtration fraction increased only in NC. Basal renal vascular resistances were greater in NP, and significantly increased after CS in both groups. Basal fractional sodium excretion (FENa) was lower in NP: after CS FENa decreased only in NC. Neither plasma renin activity, nor plasma aldosterone changed after CS. When urinary protein excretion (UP) was corrected by GFR, no change was observed after CS; by contrast, selectivity of proteinuria (as assessed by the CIgG/CTransferrin ratio) markedly increased. Our data indicate that CS induces a greater fall in the GFR in hypovolemic NP than in healthy subjects, probably because in the former GFR becomes extremely plasma flow dependent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal kallikrein responses to dietary protein: a possible mediator of hyperfiltration

We studied GFR, RPF and renal kallikrein in rats fed 9%, 25%, or 50% protein (casein) diets for 8 to 13 days. CFR and RPF increased progressively with increasing dietary protein. Renal excretion of active kallikrein (microgram/day) was 128 +/- 9, 174 +/- 11 and 228 +/- 14 in 9%, 25%, and 50% protein-fed rats, respectively (P less than 0.02 or less between groups). Prokallikrein excretion in these groups was 23 +/- 7, 77 +/- 11 and 118 +/- 15 micrograms/day, respectively (P less than 0.005 or less between groups). The in vivo renal kallikrein synthesis rate, relative to total protein synthesis, was reduced in 9% protein-fed rats (2.74 +/- 0.24) compared to rats fed 25% (3.93 +/- 0.34, P less than 0.02) or 50% protein (4.41 +/- 0.30, P less than 0.001). These changes in synthesis and excretion rates were not accompanied by changes in renal tissue levels of active or prokallikrein. In all groups, GFR and RPF correlated directly with the renal excretion of active kallikrein, prokallikrein or total kallikrein (r = 0.41 to 0.66, P less than 0.01). Treatment of 50% protein-fed rats with aprotinin, a kallikrein inhibitor, markedly lowered renal and urinary kallikrein-like esterase activity. Left kidney GFR and RPF were significantly reduced in aprotinin-treated rats compared to vehicle-treated rats (1.54 +/- 0.15 and 4.86 +/- 0.38 ml/min vs. 1.89 +/- 0.10 and 5.93 +/- 0.22 ml/min, GFR and RPF, respectively, P less than 0.05 or less).(ABSTRACT TRUNCATED AT 250 WORDS)