糖尿病大鼠肾小球及内髓集合管细胞对一氧化氮反应的异常

目的观察糖尿病大鼠肾脏中一氧化氮（ＮＯ）依赖性３′，５′环磷酸鸟苷（ｃＧＭＰ）的改变，推测ＮＯ在糖尿病肾病中的可能作用。方法分离肾小球及内髓集合管（ＩＭＣＤ）细胞，采用放免法测定ｃＧＭＰ含量。结果糖尿病大鼠肾小球ｃＧＭＰ基础水平明显升高，ＮＧ单甲基Ｌ精氨酸（ＬＮＭＡ）仅可部分纠正该异常，肾小球对Ｌ精氨酸、乙酰胆碱及硝普钠的刺激反应明显减弱。ＩＭＣＤ细胞对Ｌ精氨酸的反应也下降。结论糖尿病大鼠肾小球及ＩＭＣＤ细胞均存在ＮＯ代谢异常。     

济肾汤对糖尿病大鼠肾脏病变改善作用的机制

目的探讨济肾汤对实验性糖尿病大鼠肾脏病变改善作用的机制。方法诱发大鼠糖尿病４周后，济肾汤给药８周，评价济肾汤对糖尿病大鼠肾脏自由基代谢紊乱和非酶促糖基化作用的影响。结果济肾汤处理可明显提高糖尿病大鼠肾脏超氧化物歧化酶（ＳＯＤ）和过氧化氢酶（ＣＡＴ）活性，降低肾脏和尿液脂质过氧化物丙二醛（ＭＤＡ）水平，显著减少肾皮质５羟甲基糠醛（５ＨＭＦ）释放量和肾小球系膜区硝基四氮唑蓝（ＮＢＴ）染色强度。结论减轻肾脏自由基代谢紊乱和抑制非酶促糖基化可能是济肾汤改善糖尿病大鼠肾脏病变的重要机制。     

大鼠脑缺血后一氧化氮合酶的时相变化

探讨一氧化氮有脑缺血中的作用。方法 用分光光度法则脑缺血后ＮＯＳ活性，ＲＴＰＣＲ半定量测脑缺血后ｃＮＯＳ，ｉＮＯＳｍＲＮＡ表达水平，结果 脑缺血后１小时ＮＯＳ活性增加，４小时ＮＯＳ活性开始下降，１２小时 ＮＯＳ活性最低；脑缺血后２４小时，４８小时开始ＮＯＳ活性再镒明显升高。脑缺血后１小时，４小时ｃＮＯＳｍＲＮＡ表达增加，１２小时开始下降，２４小时明显下降，直至４８小时，脑缺血后１小时，４小时ｉＮＯ     

IgA肾病患者肾组织中增殖细胞核抗原表达

用免疫组化方法研究了２０例原发性ＩｇＡ肾病患者肾组织中增殖细胞核抗原（ＰＣＮＡ）表达。结果显示ＩｇＡ肾病患者肾组织中ＰＣＮＡ表达增加，肾小球内ＰＣＮＡ阳性细胞数、肾小管和间质中ＰＣＮＡ阳性细胞百分数均与肾组织学损害程度呈正相关；临床－病理研究显示肾小管中ＰＣＮＡ阳性细胞百分数分别与２４小时尿蛋白量、血清肌酐浓度（Ｓｃｒ）呈正相关；肾间质中ＰＣＮＡ阳性细胞百分数亦与２４小时尿蛋白量呈正相关。肾脏细胞增殖程度作为一项判断肾小球肾炎组织学损害程度和预后的指标值得进一步研究。     

黄芪当归合剂降低肾病综合征大鼠血脂机制的探讨

目的　探讨黄芪当归合剂降低肾病综合征（ＮＳ）大鼠血脂的机制。方法　采用加速型肾毒血清肾炎致ＮＳ模型。治疗组灌服黄芪当归合剂,正常组和肾病对照组灌水。检测各组血清脂谱,以Ｎｏｒｔｈｅｒｎ 杂交检测肝脏羧甲基戊二酰辅酶Ａ（ＨＭＧＣｏＡ） 还原酶和低密度脂蛋白受体（ＬＤＬＲ）ｍＲＮＡ表达。结果　肾病大鼠呈高脂蛋白血症,该组肝脏ＨＭＧＣｏＡ还原酶的ｍＲＮＡ在早期呈短暂上调（ Ｐ ＜ ０－００１） ,ＬＤＬ受体ｍＲＮＡ 表达随病程逐渐下调（ Ｐ ＜ ０－００１）;黄芪当归治疗组,血清胆固醇、甘油三酯、低密度脂蛋白和极低密度脂蛋白低于肾病对照组,虽肝脏ＨＭＧＣｏＡ 还原酶ｍＲＮＡ 无明显变化,但ＬＤＬ受体ｍＲＮＡ表达较肾病对照组显著上调（ Ｐ＜ ０－０１） 。结论　黄芪当归组显著降低ＮＳ大鼠血脂水平,这一改善脂代谢紊乱的作用可能部份是通过肝脏ＬＤＬ受体ｍＲＮＡ 表达上调而实现。     

早期肠道喂养对烧伤大鼠肠道一氧化氮合酶的影响

目的阐明烧伤大鼠经早期肠道喂养后肠组织中一氧化氮合酶（ＮＯＳ）的变化规律及其与肠粘膜血流量（ＩＭＢＦ）的关系。方法采用３０％ＴＢＳＡⅢ度烧伤大鼠模型，分为正常对照（Ｃ）组，单纯烧伤（Ｂ）组和早期喂养（ＥＦ）组，分别检测伤前及伤后０，３，６，１２，２４，４８小时肠组织中ＮＯＳ活性，包括原生型ＮＯＳ（ｃＮＯＳ）和诱导型ＮＯＳ（ｉＮＯＳ），并测定肠粘膜血流量。结果烧伤后各组ｃＮＯＳ和ＩＭＢＦ呈下降趋势，二者呈显著正相关（ｒ＝０．９７，Ｐ＜０．０１），而ＮＯＳ总活性和ｉＮＯＳ活性都呈上升趋势，ＩＭＢＦ与ｉＮ－ＯＳ和总ＮＯＳ相关不显著。烧伤后ＥＦ组ｃＮＯＳ和ＩＭＢＦ明显高于Ｂ组，ｉＮＯＳ则低于Ｂ组，ＮＯＳ总活力两组无显著差异。结论①两型ＮＯＳ中ｃＮＯＳ与ＩＭＢＦ的关系更加密切。②早期肠道喂养改善烧伤后肠道缺血状况，可能与食物对肠壁神经的刺激从而提高ｃＮＯＳ活性有关。     

卡托普利调节早期糖尿病大鼠肾脏诱生型一氧化氮合成酶基因表达

应用廓清实验和逆转录半定量聚合酶链式反应（ＰＣＲ）分析研究了卡托普利（ｃａｐｔｏｐｒｉｌ）对糖尿病早期肾血液动力学的影响及其机制。结果卡托普利可纠正４周糖尿病大鼠的肾脏高灌注、高滤过；半定量ＰＣＲ分析显示非卡托普利治疗的４周糖尿病大鼠肾脏皮、髓质诱生型一氧化氮合成酶（ｉＮＯＳ）基因表达显著上调，而卡托普利治疗鼠肾脏皮、髓质ｉＮＯＳｍＲＮＡ水平明显低于非治疗鼠。结论抑制过高的ＮＯ产生可能是卡托普利影响糖尿病早期肾血液动力学的机制之一。     

特异性环加氧酶2抑制剂对肾大部切除大鼠肾脏的保护作用

目的 探讨特异性环加氧酶（ＣＯＸ）－２抑制剂（ｒｏｆｅｃｏｘｉｂ）对５／６肾切除大鼠肾脏病变的保护作用。方法 大鼠随机分为 ４组，１假手术组，Ⅱ肾切除（ＳＮＸ）组，皿 ＳＮＸ＋ｒｏｆｅｃｏｘｉｂ组，Ⅱ ＳＮＸ＋蚓哚美辛组。６周后检测大鼠血压、肾功能、尿蛋白及尿血栓烷Ｂ。（ＴＸＢ_２），观察肾组织病理改变，并应用ＲＴ－ＰＣＲ的方法检测肾皮质内ＴＧＦ－βｍＲＮＡ的表达；免疫沉淀方法检测ＴＧＦ－β１蛋白质的表达。结果ｒｏｆｅｃｏｘｉｂ组大鼠蛋白尿水平较ＳＮＸ组显著降低（Ｐ＜０．０５）；肾小球硬化及肾小球基底膜增生程度比ＳＮＸ组明显减轻（Ｐ＜０．０５）；肾皮质ＴＧＦ－βｒｍ ＲＮＲ及蛋白质表达水平较ＳＮＸ组分别下调４０．８２％（Ｐ＜０．０１）和５６．８４％（Ｐ＜０．００１）。吲跺美辛组大鼠蛋白尿水平虽较ＳＮＸ组降低，肾皮质ＴＧＦ－β１ｍＲＮＡ及其蛋白质的表达水平较ＳＮＸ组分别下调１６．４２％和１５ ．７６％（Ｐ＞０．０５），但均无统计学意义；肾小球硬化虽较ＳＮＸ组轻，但肾间质纤维化程度较ＳＮＸ组加重。结论 特异性ＣＯＸ－２抑制剂对５／６肾大部切除大鼠肾脏病变有部分保护作用。要明确ＣＯＸ－２抑制剂产生肾保护的机制尚待进一步研究     

慢性间质性肾炎炎症细胞浸润的特点

目的　探讨慢性间质性肾炎发生发展中炎症细胞浸润与粘附因子表达的特点。方法　用雌性Ｗｉｓｔｅｒ 大鼠,皮下注射嘌呤霉素氨基核苷（ＰＡＮ） 建立慢性间质性肾炎动物模型。于注射后０ 、３ 、５ 、８、１２ 周分别检测２４ 小时尿蛋白定量,分批取出肾脏作ＨＥ染色,免疫组织化学ＡＢＣ法标记单克隆抗体ＣＤ４、ＣＤ８、ＭΦ、粘附分子１（ＩＣＡＭ１） 、ＣＤ１１ａ、ＣＤ１１ｂ、ＣＤ１８、ＣＤ４４ 、ＨＡ、ＴＣＲ（α,β）、ＭＨＣⅡ。结果　实验组第３ 周始２４ 小时尿蛋白量逐渐增加,与对照组比较有显著性差异,ＨＥ染色可见肾间质炎症细胞浸润,ＣＤ４ 阳性、ＴＣＲ阳性、ＩＣＡＭ１ 阳性细胞增多,第８ 周２４ 小时尿蛋白量达高峰,出现肾间质纤维化,肾小管萎缩、ＩＣＡＭ１、ＴＣＲ、ＣＤ４４、ＨＡ、ＣＤ１１ａ、ＣＤ１１ｂ、ＣＤ１８、ＭＨＣ Ⅱ阳性细胞数达高峰;第１２ 周,多种细胞因子表达及２４ 小时尿蛋白定量呈下降趋势。结论　ＣＤ４ 阳性细胞的浸润增殖,启动了多种细胞因子表达,在慢性间质肾炎发生发展中起重要作用。     

系膜增殖性肾炎患者肾生存率的研究

目的为了探讨系膜增殖性肾炎（ＭｅｓＰＧＮ）肾生存情况。方法采用Ｋａｐｌａｎ－Ｍｅｉｅｒ方法观察了１８３例１５～６０岁ＭｅｓＰＧＮ患者肾生存率（ＫＳＲ）。结果肾活检后３、６、１０年，ＫＳＲ分别是８８％、８１％、７５％；根据肾小球系膜损害程度将患者分３组，结果系膜损害越重，ＫＳＲ愈低（Ｐ＜０．０１）；分析了肾活检时高血压、尿蛋白排泄量与ＫＳＲ的关系，结果肾活检时，有高血压、尿蛋白≥３．５ｇ／ｄ，则肾生存率较对照组差。结论ＭｅｓＰＧＮ患者ＫＳＲ与肾小球系膜损害程度，高血压、大量尿蛋白有关     

High glucose increases inducible NO production in cultured rat mesangial cells. Possible role in fibronectin production.

BACKGROUND/AIM: Increased nitric oxide (NO) generation and action have been suggested to be associated with glomerular hyperfiltration and increased vascular permeability early in diabetes. However, previous studies have primarily focused on the constitutive nitric oxide synthase (cNOS) pathway present in endothelial cells, and the role of the inducible NOS (iNOS) pathway in diabetic nephropathy has remained unclear. This study examined whether high glucose modulates NO synthesis by the iNOS pathway in rat mesangial cells. In addition, the effect of inhibition of the iNOS pathway on fibronectin production was determined to examine the role of the iNOS pathway in high glucose-induced extracellular expansion by mesangial cells. METHODS: NO synthesis by the iNOS pathway was evaluated by nitrite and iNOS mRNA and protein productions. The effects of protein kinase C (PKC) inhibitor and aldose reductase inhibitor on the iNOS mRNA expression and aminoguanidine, a relatively specific inhibitor of the iNOS on fibronectin protein production were examined. RESULTS: High 30 mM glucose concentration led to significant increases in nitrite production of rat mesangial cells upon stimulation with lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) compared with control 5.6 mM glucose concentration. Mesangial iNOS mRNA expression and protein production also increased significantly in response to high glucose. The addition of calphostin C, a PKC inhibitor, and 6-bromo-1,3-dioxo-1H-benz[d,e]isoquinoline-2(3H)-acetic acid, an aldose reductase inhibitor, significantly suppressed the enhancement of iNOS mRNA expression in high glucose concentration. High glucose also significantly increased fibronectin protein production of mesangial cells upon stimulation with LPS plus IFN-gamma compared to control glucose. Aminoguanidine reversed this high glucose-induced fibronectin production at dose inhibiting iNOS mRNA expression. CONCLUSIONS: These results indicate that high glucose enhances cytokine-induced NO production by rat mesangial cells, and that the activation of PKC and aldose reductase pathway may play a role in this enhancement. In addition, high glucose-induced NO production by the iNOS pathway may promote extracellular matrix accumulation by mesangial cells under certain condition.     

Analysis of NO-synthase expression and clinical risk factors in human diabetic nephropathy.

BACKGROUND: Changes of renal nitric oxide (NO) production have been associated with glomerular hyperfiltration, vascular permeability, albuminuria, glomerulosclerosis and tubulointerstitial fibrosis. Several studies demonstrated an up- as well as downregulated expression of NO-synthases (NOS) in experimental diabetic nephropathy. It is still not yet specified whether the regulation and activity of NOS is changed in human diabetic nephropathy. METHODS: Renal biopsies and clinical data of 45 patients with diabetic nephropathy and of 10 control subjects were investigated. Glomerular and cortical endothelial NOS (eNOS) and inducible NOS (iNOS) expression were assessed by immunohistochemical staining and related to clinical data such as the duration of diabetes, insulin therapy and arterial hypertension, albuminuria/proteinuria, eGFR according to the formula modification of diet in renal disease (MDRD), presence of vascular complications or diabetic retinopathy. RESULTS: The mean age of patients at biopsy was 60.3 years and the mean duration of diabetes 12.9 years. Expression of cortical and glomerular eNOS was increased in type 2 diabetes (P < 0.05). Increased expression of glomerular and cortical eNOS correlated with more severe vascular complications (r = 0.44; P < 0.05). Glomerular eNOS was strongly increased among different degrees of proteinuria (P < 0.01). In contrast to expression levels of eNOS, the glomerular expression pattern of iNOS changed from an endothelial pattern in glomeruli with preserved morphology towards expression predominantly by inflammatory cells. CONCLUSIONS: Thus, increased eNOS expression by the renal endothelium could be demonstrated in type 2 diabetic nephropathy, whereas iNOS was unchanged but spatially differentially expressed. The eNOS expression was related to vascular lesions and the degree of proteinuria.     

Nitric oxide synthase isoforms and glomerular hyperfiltration in early diabetic nephropathy

This study tested the hypothesis that nitric oxide (NO)-mediated renal vasodilation due to the activity of the inducible nitric oxide synthase (iNOS) contributes to glomerular hyperfiltration in diabetic rats. Two weeks after induction of diabetes mellitus by streptozotocin, mean arterial BP (MAP), GFR (inulin clearance), and renal plasma flow (RPF) (para-aminohippurate clearance) were measured in conscious instrumented rats. Diabetic rats had elevated GFR (3129 +/- 309 microl/min versus 2297 +/- 264 microl/min in untreated control rats, P < 0.05) and RPF (10526 +/- 679 microl/min versus 8005 +/- 534 microl/min), which was prevented by chronic insulin treatment. Intravenous administration of 0.1 and 1 mg of L-imino-ethyl-lysine (L-NIL), an inhibitor of iNOS, did not affect MAP, GFR, or RPF, either in diabetic or control rats. A higher L-NIL dose (10 mg) increased MAP and decreased RPF in diabetic rats significantly (n = 6, P < 0.05), but not in controls (n = 6). In addition, 0.1 mg of NG-nitro-L-arginine methyl ester (L-NAME), a nonselective blocker of NOS isoforms, decreased GFR (2389 +/- 478 microl/min) and RPF (7691 +/- 402 microl/min) in diabetic animals to control levels, while renal hemodynamics in normoglycemic rats were not altered. Higher L-NAME doses (1 and 10 mg) reduced GFR and RPF in diabetic and control rats to identical levels. In glomeruli isolated from diabetic and control rats, neither iNOS mRNA nor iNOS protein expression was detected. In contrast, increased protein levels of endothelial constitutive NOS (ecNOS) were found in glomeruli of diabetic rats compared with controls. By immunohistochemistry, ecNOS but not iNOS staining was observed in the endothelium of preglomerular vessels and in diabetic glomeruli. These results support the notion that increased NO availability due to greater abundance of ecNOS contributes to the pathogenesis of glomerular hyperfiltration in early experimental diabetic nephropathy. In contrast, we found no functional or molecular evidence for increased glomerular expression and activity of iNOS in diabetic rats.     

Association of renal injury with nitric oxide deficiency in aged SHR: prevention by hypertension control with AT1 blockade

BACKGROUND: Aged spontaneously hypertensive rats (SHR) develop end-stage renal disease resembling that of uncontrolled essential hypertension in humans. Nitric oxide (NO) and angiotensin II (Ang II) play an important role in the regulation of blood pressure and the growth of vascular smooth muscle and renal mesangial cells. The relationship between renal NO system, Ang II activity and renal injury in aged SHR is not fully understood. METHODS: The 8-week-old SHR were randomized into losartan-treated (30 mg/kg/day for 55 weeks) and vehicle treated groups. The age-matched Wistar-Kyoto rats (WKY) served as controls. Renal histology and tissue expressions of endothelial and inducible NO synthases (eNOS and iNOS) and nitrotyrosine were examined at 63-weeks of age. RESULTS: Compared to the WKY group, untreated SHR showed severe hypertension, proteinuria, renal insufficiency, a twofold decrease in renal tissue eNOS and iNOS expressions and massive nitrotyrosine accumulation. This was associated with severe glomerulosclerosis, tubular atrophy and interstitial fibrosis. Losartan therapy normalized blood pressure, prevented proteinuria and renal insufficiency, abrogated the fall in renal eNOS and iNOS protein contents, mitigated renal nitrotyrosine accumulation, and prevented the histological abnormalities found in the untreated SHR. CONCLUSIONS: Aged SHR exhibit severe renal lesions with acquired NO deficiency that are prevented by hypertension control with AT1 blockade. These findings point to the possible role of NO deficiency in the pathogenesis of renal lesions in aged SHR.     

丹参对大鼠缺血再灌注肾组织一氧化氮合成酶mRNA表达的影响

目的：探讨丹参对肾缺血再灌注损作保护效应的分子机制。方法：以大鼠缺血再灌汪肾损伤为模型，采用组织细胞原位杂交有图像分析技术技术，检测cNOS（eNOS和nNOS）及iNOSmRNA在缺血再灌注肾组织中的表达，并测定肾组织NOS总活性有血肌酐（Cr）。结果：①3种NOS在正常肾组织中均有表达，其中eNOS表达最丰富，cNOS／iNOS比值为2．29。②缺血时，肾组织NOS总活性显著下降，3种NOSmRNA在皮质、髓质有小球中的表达均下调，以eNOS最显著，cNOS／iNOS比值呈下降（2．01）趋势。③再灌注后，3种NOSmRNA的表达明显上调，以iNOSmRNA最明显，cNOS／iNOS的比值降至1．77。④肾缺血注射丹参后再灌注，iNOSmRAN表达明显下调，而nNOSmRAN则显著上调，cNOS／iNOS比值处于正常范围（2．14），Cr含量下降至正常水平。结论：①皮质肾小管上皮中iNOS活性升同与再灌汪后肾功能进一步受损密切相关。②缺血再灌注肾损伤中，丹参抑制iNOSmRNA和促进cNOSmRNA的表达是其介导肾保护效应的重要分子机制。③cNOS／iNOS比值的恒定对肾血流量和肾小球滤过率（GFR）的调节可能具有重要的意义。     

卡托普利对缺血-再灌注鼠心肌一氧化氮及其合酶活性的影响

目的　研究一氧化氮 (NO)和一氧化氮合酶 (NOS)在心肌再灌注损伤中的作用 ,探讨卡托普利(captopril)对缺血 -再灌注鼠心肌保护的机制。　方法　采用 L angendorff离体鼠心灌流模型 ,将 18只 SD大白鼠随机分为 3组 (每组 6只 ) ,对照组、缺血 -再灌注组、卡托普利组。观察心肌 NOS同工酶活性、过氧化物歧化酶活性、丙二醛含量、肌酸激酶含量和冠脉流出液 NO的变化。　结果　缺血 -再灌注组与对照组比较心肌诱导型 NOS(i NOS)活性增高 (P<0 .0 0 1) ,而心肌原生型 NOS(c NOS)活性及总 NOS活性显著降低 (P<0 .0 0 1,0 .0 5 ) ,冠脉流出液 NO含量下降(P<0 .0 1)。卡托普利组再灌注 30分钟 ,心肌 i NOS活性低于缺血 -再灌注组 (P<0 .0 1) ,c NOS活性和总 NOS活性高于缺血 -再灌注组 (P<0 .0 1,0 .0 5 ) ,再灌注期间冠脉流出液 NO水平高于缺血 -再灌注组 (P<0 .0 1) ,心肌损伤较缺血 -再灌注组减轻。　结论　心肌 NOS同工酶活性及 NO产生的失常是心肌再灌注损伤的重要机制之一 ,卡托普利可通过调节心肌 NOS同工酶活性 ,维持正常的 NO水平 ,起到心肌保护作用。     

一氧化氮及其合酶在心肌缺血再灌注损伤中作用的研究

目的：用鼠的离体工作心脏研究心肌缺血再灌注损伤一氧化氮（ＮＯ）、ＮＯ合酶（ＮＯＳ）的作用。方法：ＲＴ－ＰＣＲ定量检测心肌组织结构型ＮＯＳ（ｃＮＯＳ）的ｍＲＮＡ表达,测定心肌组织的ｃＮＯＳ、诱导型ＮＯＳ（ｉＮＯＳ）及冠状动脉动脉冠脉）流出液的ＮＯ,同时检测心脏缺血再灌注前后的心功能变化。并分别于次序停跳液中加用缓激肽（ＢＫ）、Ｌ－精氨酸及ＢＫ加Ｌ－精氨酸,观察其对心肌缺血再灌注损伤的影响。结果：心肌     

Activation of mRNA expression of collagen,collagenase and its inhibitor on renal biopsy specimens in patients with IgA nephropathy

Summary: In situ hybridization of mRNA for collagen IV, collagen VI, stromelysin (MMP-3) and TIMP1 was examined in renal biopsy specimens from patients with IgA nephropathy (IgAN) or diabetic nephropathy with various degrees of tissue damage. The majority of cells in the glomeruli expressed these mRNA almost simultaneously, but a few cells demonstrated positive expression for only one of these probes. There was a parallel relationship between the degree of tissue damage and that of mRNA expressions of these probes in patients with IgAN, while patients with diabetic nephropathy showed a reverse relationship between these two parameters. It is concluded that patients with mesangial proliferative glomerulonephritis expressed mRNA for collagen collagenase and its inhibitor in the glomeruli in parallel with the progress of tissue damage. In contrast, glomerular samples from patients with diabetic nephropathy showed that there was an inverse relationship between tissue damage and expression of mRNA. It is concluded that expression of collagen, collagenase and its inhibitor parallels the progression of glomerular changes in IgAN, but such parallel expression was not observed in patients with diabetic nephropathy.     

Magnesium supplementation prevents chronic cyclosporine nephrotoxicity via adjusting nitric oxide synthase activity

INTRODUCTION: Nitric oxide synthase (NOS) is a protective factor for chronic cyclosporine nephrotoxicity by virtue of adjusting the production of nitric oxide (NO). The aim of this study was to explore the role of NOS in the effect of magnesium supplementation to prevent chronic cyclosporine nephrotoxicity. METHODS: Rats maintained on a low-salt diet were divided into three groups: normal controls, cyclosporine group (CsA 15 mg x kg(-1) x d(-1) subcutaneously) and CsA + Mg2+ group (CsA subcutaneously and dietary supplementation with 0.6% Mg enriched by MgCl2). On day 28, plasma Mg2+, plasma creatinine, NOS activity, and NO content in renal tissue were examined. The renal expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in kidneys was determined by an immunohistochemistry technique. The lesions of chronic cyclosporine nephrotoxicity were identified by HE and PAS stains as well as electron microscope. RESULTS: After 28 days of CsA administration, characteristic histological lesions of chronic cyclosporine nephotoxicity were observed, including arteriolopathy, tubular atrophy and interstitial fibrosis. Giant mitochondria and microcalcifications were observed by electron microscopy. Simultaneously, constitutive nitric oxide synthase (cNOS) activity in kidneys was increased, but NO content did not increase correspondingly (P < .05) compared with normal controls. Dietary supplementation with Mg2+ ameliorated the CsA-induced histological lesions. cNOS activity was decreased to normal levels and NOS was increased (P < .05) compared with animals that only received CsA. CsA and magnesium supplementation did not change iNOS activity. CONCLUSIONS: Dietary supplementation with Mg2+ seems to improve renal function and almost abolish CsA-induced histological lesions via altering the abnormal activation of cNOS in this model.