氨氯地平产生的兔股动脉舒张部分由NO介导

目的 研究氨氯地平舒张周血管的作用是否与激活一氧化氮合酶（NOS）有关。方法 利用家兔股动脉恒流灌注模型，观察股动脉内灌注有效浓度的氨氯地平后灌注压的变化及NOS抑制剂L－NAME对其作用的影响。结果 氨氯地平缓慢平稳降低周围血管阻力，NOS抑制剂L－NAME能部分阻断这种作用。结论 氨氯地平产生的周围血管舒张作用部分通过刺激NO生成而实现。     

吸烟对大鼠肺动脉压和一氧化氮合酶的影响

目的 :探讨长期吸烟对大鼠肺动脉压及一氧化氮合酶的影响。方法 :SD雄性大鼠 40只 ,随机分为吸烟组和对照组 ,吸烟组暴露于点燃之烟卷 ,每日 6 h,于 9个月时检测吸烟组及对照组大鼠的肺动脉平均压 （m PAP）、血清一氧化氮 （NO）、肺动脉结构型一氧化氮合酶 （c NOS）和诱导型一氧化氮合酶 （i NOS）。结果 :吸烟组大鼠 m PAP明显高于对照组 ,血清 NO浓度与对照组相比明显减低 ,吸烟组肺细小动脉 c NOS平均吸光度值较对照组明显降低 ,吸烟组大鼠肺细小动脉 i NOS的平均吸光度值较对照组明显增高。结论 :烟雾可致肺动脉高压的形成 ,抑制肺细小动脉 c NOS表达、促进肺细小动脉 i NOS表达可能为其重要作用机制之一。     

高浓度Ca2+对大鼠脑线粒体呼吸功能的影响

应用分离的大鼠脑线粒体,给予外源性高浓度Ca^2＋及一氧化氮合酶（NOS）抑制剂-L-硝基-精氨酸甲酯（L—NAME）,检测一氧化氮（NO）含量及线粒体呼吸功能。结果显示高浓度Ca^2＋引起NO含量升高,线粒体呼吸功能降低,L—NAME通过抑制NOS活性使NO合成减少,对线粒体呼吸功能有保护作用。认为,外源性高浓度Ca^2＋可激活线粒体NOS,使NO合成增多,导致线粒体呼吸功能降低。     

肝硬化大鼠全胃肠外营养时一氧化氮和一氧化氮合酶活性的变化及意义

目的 观察一氧化氮（NO）、一氧化氮合酶（NOS）活性在肝硬化大鼠全胃肠外营养（TPN）时的变化,并探讨其意义。方法 Wistar大鼠分为3组：正常组8只,肝硬化对照组6只,肝硬化TPN组7只。测定血清NO浓度、肝脏NO含量和肝脏NOS比活性,观察肝脏β－BADPH黄递酶组化染色。结果 除TPN组一只大鼠因输液过快,肺水肿死亡外,其余大鼠均成活。血清NO浓度、肝脏NOS比活性,肝硬化对照组比正常组升高明显（P＜0．05）,肝硬化TPN级比肝硬化对照组升高明显（P＜0．05）。肝脏NO含量,肝硬化对照组比对照组升高明显（P＜0．05）,但肝硬化TPN组比肝硬化对照组降低明显（P＜0．05）。肝脏β－NADPH黄递酶组化染色,正常组为－,肝硬化对照组为＋,肝硬化TPN组为＋＋。结论 NO可能是一种抗肝损伤因子,损伤因子存在时,表现为肝脏NOS活性增强,当肝脏NO含量减少时,表现为肝脏损害的加重。     

清肠栓对溃疡性结肠炎大鼠一氧化氮和一氧化氮合酶活性的影响

目的：观察不同剂量清肠栓治疗溃疡性结肠（UC）的作用及其对一氧化氮（NO）和一氧化氮合酶（NOS）活性的影响。方法：将动物随机分成高、中、低剂量清肠栓组、SASP组、模型组、空白组,除空白组外其余5组动物分别用三硝基苯磺酸（TNBS）建立大鼠溃疡性结肠炎模型,连续用药2周后取结肠组织,采用改良的G法、分光光度法分别测定其NO含量和NOS活性。结果：模型组大鼠NO、NOS含量较空白组明显降低,其他各组均有不同程度的增高,尤其以清肠栓高剂量组的增高为明显。结论：TNBS急性损伤使结肠组织的NO、NOS活性发生改变,可能是UC发生的重要机制。中药复方清扬栓具有调控NO及NOS活性的作用,是有效治疗UC的可能机制之一。     

多巴胺系统及L-精氨酸/一氧化氮通路在大鼠心肌肥大中的作用研究

目的 探讨多巴胺系统及L-精氨酸／一氧化氮（L—Arg／NO）通路在大鼠心肌肥大动物模型中的作用及相关机制。方法 采用腹主动脉缩窄术复制大鼠心肌肥大动物模型。将Wistar大鼠随机分为4组：①腹主动脉缩窄术（AC）组；②假手术（SO）组；③L-精氨酸（L—Arg）组；④左旋硝基精氨酸甲酯（L—NAME）组。通过心肌肥大指数，心肌组织胶原染色，心功能检测等方法分析各组大鼠心肌组织肥大状况：采用RT—PCR和Western blot结合图像分析系统，观察药物干预后，心肌组织中多巴胺受体D1、D2mRNA和蛋白质表达变化：借助紫外分光光度计，分析心肌组织匀浆中一氧化氮（NO）水平和一氧化氮合酶（NOS）活性。结果 AC组左心肥大明显．表现为室内压显著升高，胶原增多；与SO组比较，腹主动脉缩窄术后D1、D2mRNA和蛋白质表达均明显降低（P〈0.01），NO、NOS水平明显下降（P〈0.01）；应用NOS抑制剂L-NAME预处理能够促进肥大的发生。使用NO合成的前体L-Arg干预，则抑制肥大发生。结论 压力负荷加大能引起心肌肥大。其机制可能与NO合成减少有关：大鼠心肌细胞内存在多巴胺受体D1、D2mRNA和蛋白质表达，心肌肥厚时二者均明显减低。     

肝硬化大鼠食管一氧化氮合酶分布定位研究

目的探讨一氧化氮（ＮＯ）在肝硬化食管静脉曲张及血流动力学改变中的作用。方法应用还原型辅酶Ⅱ－黄递酶（ＮＡＤＰＨ－ｄ）组化染色观察ＣＣＩ４所致肝硬化大鼠食管下段一氧化氮合酶（ＮＯＳ）分布；应用荧光法检测大鼠食管组织匀浆及血清中ＮＯ含量；应用５７Ｃｏ标记微球测定大鼠血流动力学指标。结果肝硬化鼠食管粘膜及粘膜下血管内皮ＮＯＳ呈强阳性反应，而正常鼠则呈弱阳性或阴性反应；肝硬化大鼠食管及血清中ＮＯ含量显著升高。且全部出现门脉高压和高动力循环状态。结论ＮＯ在肝硬化大鼠食管静脉曲张及血流动力学改变中可能起重要作用。     

硫化氢供体对实验性门静脉高压及内源性一氧化氮/一氧化氮合酶体系的影响

目的探讨硫化氢供体一硫氢化钠（sodium hydrosulfide，NaHS）对大鼠门静脉高压及内源性一氧化氮（nitric monoxide，NO）／一氧化氮合酶（nitricoxide synthase，NOS）体系的影响。方法将30只健康成年雄性sD大鼠随机分为4组：部分门静脉结扎（partly portal vein ligation，PPVL）组（10只）、PPVL＋NariS组（10只）、假手术组（5只）和正常组（5只）。PPVL组和PPVL＋NaHS组行部分门静脉结扎术建立门静脉高压的动物模型。模型制作14天后，分别测定各组大鼠的门静脉压力（PVP）和平均动脉压力（MAP）；采用免疫组织化学检测大鼠肝细胞中一氧化氮合酶（NOS2、NOSS）的蛋白水平表达情况，RT-PCR方法检测大鼠肝组织中NOS2和NOS3的mRNA水平的表达情况。结果术后14d，假手术组和正常组比较，各项检测指标无显著差异，NOS2蛋白及mR-NA水平未见明显表达；NOS3蛋白及mRNA表达水平无显著差异。PPVL组与假手术组比较，PVP明显升高（P〈0．05），MAP则下降（P〈0．05），PPVL＋NaHS组与PPVL组相比较，PVP进一步升高（P〈0．05），MAP则进一步降低（P〈0．05）。PPVL组和PPVL＋NaHS组NOS2在蛋白及mRNA水平均有表达，且后者NOS2蛋白及mRNA表达水平减少（P〈0．05）。4组之间NOS3的蛋白及mRNA表达水平则无显著差异。结论H2S参与了门静脉高压的形成与发展，NaHS可以加重门静脉高压，其作用可能与NO／NOS2体系有关。．     

高血压大鼠主动脉一氧化氮合成途径的变化

目的 观察高血压大鼠主动脉内膜，中膜和外膜一氧化氮合成途径的改变，并探讨其可能的病理生理意义。方法 Wistar大鼠缩窄腹主动脉复制高血压模型，动物随机分为对假手术组和高血压。取大鼠主动脉，分离血管内膜，中膜和外膜。分别测定其亚硝酸盐（NO2^-)生成量，一氧化氮合酶（NOS）活性及L－精氨酸（L－Arg)转运，免疫组化染色检测诱导型一氧化氮合酶（iNOS)的分布。结果 与假手术组相比，高血压大鼠血中一氧化氮代谢产物（NOx)高26．2％（P＜0．05）；主动脉NO2^-生成低65．8％（P＜0．01），中膜及外膜孵育液的NO2^-生成量分别高59．6％和123．6％（均P＜0．01）；主动脉内膜NOS活性低59．3％（P＜0．01），中膜和外膜NOS活性分别高62．6％和118．7％（均P＜0．01），血管内膜L－Arg转运率低62．5％（P＜0．01），中膜和外膜L－Arg转运率分别高53．7％和99．8％（均P＜0．01）。iNOS免疫组化染色显示，高血压大鼠血管中膜和外膜尤其是外膜iNOS阳性染色明显增强。结论 高血压大鼠血管管一氧化氮合成与代谢发生改变，血管内膜L－Arg/NOS/NO途径受抑，而中膜和外膜尤其是外膜的L－Arg/NOS/NO系统的活性增强，血管生成的NO增多。提示血管中膜和外膜源NO增多在高血压时可能具有一定的代偿作用。     

舒芬太尼对2型糖尿病大鼠离体胸主动脉血管内皮功能的影响

目的：舒芬太尼对2型糖尿病大鼠离体胸主动脉血管内皮功能的影响。方法将16只健康雄性Wistar大鼠随机分为正常组（N组）、糖尿病组（D组）,每只大鼠迅速分离胸主动脉并取4段动脉血管环,4段血管环分别给予生理盐水（C组）、舒芬太尼7×10^-11mol/L（S1组）、2×10^-10mol/L（S2组）、1×10^-9mol/L（S3组）处理,采用离体血管环灌流法,通过比较KCl预收缩和给予累积浓度的NE收缩观察血管张力G1、G2变化幅度,计算血管环收缩幅度（G2/G1×100％）来反映血管内皮功能;随后采用ELISA酶联免疫法,对各组血管环组织进行研磨、离心取上清液,观察不同浓度舒芬太尼作用后血管内皮一氧化氮（NO）、一氧化氮合酶（NOS）定量表达情况,来反映对血管内皮的作用效果。结果与NC组相比,NS2组、NS3组血管环收缩幅度降低,组织匀浆NO、NOS表达升高（P＜0．05）;与DC组相比,DS1组、DS2组、DS3组收缩幅度降低,组织匀浆NO、NOS表达升高（P＜0．05）;与DS2组相比,DS3组收缩幅度组显著降低,组织NO、NOS明显升高（P＜0．05）。结论不同浓度舒芬太尼对糖尿病大鼠离体胸主动脉血管有抑制收缩作用,高浓度作用显著,其机制可能与血管内皮因子NO表达升高有关,而NOS是其生物转化的关键酶。     

The role of nitric oxide in the pathogenesis of systemic and splanchnic vasodilation in cirrhotic rats before and after the onset of ascites.

BACKGROUND: The role of nitric oxide (NO) in the pathogenesis of splanchnic arterial vasodilation in cirrhosis has been recently debated by some experimental studies. AIMS: We investigated the role of NO in the pathogenesis of the splanchnic arterial vasodilation along the course of CCl(4)-induced experimental cirrhosis. METHODS: We analyzed the effect on mean arterial pressure (MAP), cardiac output (CO), total peripheral resistance (TPR), and resistance in the superior mesenteric artery (RSMA), before and after the administration of a unspecific NO synthase (NOS) inhibitor (Nomega-nitro-L-arginine-methyl-ester, L-NAME) and a specific NOS2 inhibitor (L-N-(1-iminoethyl)-lysine, L-NIL) to cirrhotic rats with and without ascites, and to control rats. NOS2 and NOS3 protein expression was also assessed in systemic and splanchnic arteries of these animals. RESULTS: L-NAME in cirrhotic rats markedly improved MAP, and TPR and decreased CO regardless of whether they had ascites or not. L-NIL did not produce any significant effect on systemic haemodynamics in control and cirrhotic rats. NOS3 overexpression in the aorta of cirrhotic animals paralleled the progression of the liver disease. L-NAME increased RSMA in cirrhotic rats, but this effect was much less intense in rats with ascites. L-NIL had an effect only on RSMA in rats with ascites, which was of a similar extent to that produced by L-NAME. Western blot experiment showed a faint overexpression of NOS3 in the mesenteric artery of cirrhotic rats with and without ascites and a clear induction of NOS2 only in the mesenteric artery of rats with ascites. Conclusions: These results indicate that NO contributes significantly to the pathogenesis of arterial splanchnic circulation in the early stages of experimental cirrhosis but has only a minor role in its maintenance after the development of ascites. Furthermore, the expression of the different NOS isoforms varies along the course of the liver disease.     

Chronic administration of aminoguanidine reduces vascular nitric oxide production and attenuates liver damage in bile duct-ligated rats.

BACKGROUND: Nitric oxide (NO) has been implicated in the pathogenesis of liver cirrhosis. This study investigated the activity of nitric oxide synthase (NOS) in cirrhosis induced by bile duct-ligation (BDL) with NOS inhibitors. METHOD: Three days after operation, rats were randomized to receive aminoguanidine (AG, 25 mg/kg/day) or L-N(G)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg/day) for 21 days. RESULTS: Vascular NO production, which was increased in BDL cirrhotic rats, was reduced by 75% with AG but not L-NAME chronic administration. AG treatment attenuated liver damage, while L-NAME aggravated it. AG significantly suppressed inducible NOS (iNOS) expression in aorta of BDL rats at both mRNA and protein level, but much less efficient in reducing it in liver. In contrast, endothelial NOS (eNOS) expression was not markedly affected. Calcium-independent NOS activity, which was dramatically increased in aorta of BDL rats, was abolished by AG treatment. In liver, however, both calcium-dependent and -independent NOS activity were increased by AG treatment. CONCLUSION: Chronic administration of AG could reduce systemic NO levels as well as suppress iNOS expression and activity in aorta of BDL rats. It also improved liver function, possibly because of its ability to increase hepatic NOS activity, and to correct the systemic hemodynamic disorders by decreasing vascular NO production.     

Effect of L—NAME on nitric oxide and gastrointestinal motility alterations in cirrhotic rats

AIM: To invsstigare the effect of L-NAME on nitric oxide andgastriubtestubal motility alterations in cirrhotic ratsMETHODS: Rats with cirrhosis induced by carbontetrachloride were randomly divided into two groups, one( n= 13) receiving 0. 5 mg@ kg-1 per clay of NG-nitro-L-argininemethyl ester (L-NAME), a nitric oxide synthase inhibitor,for 10 days, whereas the other group ( n = 13) and control( n = 10) rats were administrated the same volume of 9 g@ L-1saline.Half gastric emptying time and 2 h residual rate weremeasured by SPECT, using 99m Tc-DTPA-labeled bariumsuifate as test meal. Gastrointestinal transition time wasrecorded simultaneously. Serum concentration of nitrcoxide (NO) was determined by the kinetic cadmiunreduction and colorimetric methods. ImmunohistochemicalSABC method was used to observe the expression anddistribution of three types of nitric oxide synthase (NOS)isoforms in the mt gastrointestinal tract. Western blot wasused to detect expression of gastrointestinal NOS isoforms.RESULTS: Half gastric emptying time and trans-gastrointestinal time were significantly prolonged( 124.0 ± 26.4min; 33.7± 8.9min;72.1 ± 15.3 min; P＜0.01), (12.4±0.5h; 9.5±0.3 h; 8.2±0.8 h; P＜0.01), 2h residual rate wasraised in cirrhotic rots than in controls and cirrhotic ratstreated with L-NAME(54.9± 7.6 % ,13.7 ± 3.2 %, 34.9± 10.3%, P＜ 0.01). Serum concentration of NO was significantlyincreased in cirrhotic rots than in the other groups (8.20 ± 2.48)μmol@L-1, (5.94± 1.07) μmol@L-1 ,and control (5.66± 1.60) tμmol@L-1, P＜ 0.01. NOS staining intensities which weremainly located in the gastrointestinal tissues were markedlylower in cirrhotic rats than in the controls and cirrhotic ratsafter treated with L- NAME.CONCLUSION: Gastrointestinal motility was remarkablyinhibited in cirrhotic rats, which could he alleviated by L-NAME. Nitric oxide may play an important role in theinhibition of gastrointestinal motility in cirrhotic rats.     

内源性一氧化氮在哮喘大鼠气道高反应性中的作用

目的　利用一氧化氮合成前体Ｌ精氨酸（ＬＡｒｇ） 和一氧化氮合酶抑制剂亚硝基Ｌ精氨酸甲酯（ＬＮＡＭＥ）研究内源性一氧化氮在哮喘大鼠气道高反应性中的作用,探讨支气管哮喘的发病机制。方法　用卵白蛋白作为致敏原制备哮喘大鼠模型,建立大鼠离体气管环张力的测定方法,并用ＬＡｒｇ、ＬＮＡＭＥ和ＬＡｒｇ＋ ＬＮＡＭＥ孵育离体气管环,观察气管环乙酰胆碱浓度反应曲线和最大收缩反应的变化,同时观察去上皮对哮喘大鼠气道反应性的影响。结果　哮喘大鼠（１０ 只） 离体气管环经ＬＮＡＭＥ１０５ ｍｏｌ／Ｌ孵育后对乙酰胆碱的最大收缩反应从孵育前（１２４±３９） ｍｇ 上升到（１８７ ±５３） ｍｇ,孵育前、后最大收缩反应比较差异具有显著性（ Ｐ＜ ０．０１）,浓度反应曲线上移,而ＬＡｒｇ 可以逆转ＬＮＡＭＥ的作用,单用ＬＡｒｇ ２×１０５ ｍｏｌ／Ｌ和ＬＡｒｇ１０３ ｍｏｌ／Ｌ孵育气管环,对哮喘大鼠气管环的最大收缩反应和浓度反应曲线与对照组比较,差异无显著性（ Ｐ＞ ０．０５） 。去上皮哮喘大鼠气管环的反应性与上皮完整气管环比较差异有显著性（ Ｐ＜ ０．００５） ,而ＬＡｒｇ、ＬＮＡＭＥ＋ ＬＡｒｇ 和ＬＮＡＭＥ孵育去上     

Nitric oxide synthase distribution in esophageal mucosa and hemodynamic changes in rats with cirrhosis

SubjectheadingsesOPhagUs;nitricoxidesynthase;livercirrhosis;hemodynamicsINTRODUCTIONCirrhosiswithportalhypertensionisassociatedwithhyperdynamiccirculationcharacterizedbygeneralizedvasodilationandincreasedcardiacoutputandsplanchnicregionalbloodflows.EndogenousNO,averypotentvasodilatorfactor,mayplayaveryimportantroleinthepathogenesisofhemodynamicchangesincirrhosis.ItisnuclearwhetherNOisinvolvedinthepathogenesisofesophagealvaricesasoneofseverecomplicationsofhepaticcirrhosis.Thepresentstud…     

反流性食管炎时食管一氧化氮合酶表达的实验研究

目的：初步探讨反流性食管炎时食管ＮＯＳ的表达。方法：采用幽门半缝扎＋贲门肌切开术制备反流性食管炎动物模型,采用ＮＡＤＰＨ－ｄ组化染色观察食管ＮＯＳ表达,测定食管组织ＮＯ含量。结果：食管炎组大多呈ＮＯＳ强阳性反应,阳性率明显高于正常对照组（Ｐ＜０．００１）,食管组织ＮＯ含量也明显高于正常对照组（术后２４小时比较Ｐ＜０．０１,术后４８小时,７２小时比较均Ｐ＜０．０５）。结论：胃－食管反流可引起食管上皮粘膜ＮＯＳ的过度表达,过多的ＮＯ可能发挥着重要的作用。     

Nitric oxide synthase inhibitors protect against brain and liver damage caused by acute malathion intoxication

Objective: To investigate the effect of NG-nitro-L-arginine methyl ester(L-NAME), a nonselective nitric oxide synthase(NOS) inhibitor, and 7-nitroindazole(7-NI), a selective neuronal NOS inhibitor, on oxidative stress and tissue damage in brain and liver and on DNA damage of peripheral blood lymphocytes in malathion intoxicated rats. Methods: Malathion(150 mg/kg) was given intraperitoneally(i.p.) along with L-NAME or 7-NI(10 or 20 mg/kg, i.p.) and rats were euthanized 4 h later. The lipid peroxidation product malondialdehyde(MDA), nitric oxide(nitrite), reduced glutathione(GSH) concentrations and paraoxonase-1(PON-1) activity were measured in both brain and liver. Moreover, the activities of glutathione peroxidase(GPx) acetylcholin?esterase(ACh E), and butyrylcholinesterase(BChE), total antioxidant capacity(TAC), glucose concentrations were determined in brain. Liver enzyme determination, Comet assay, histopathological examination of brain and liver sections and inducible nitric oxide synthase(iNOS) immunohistochemistry were also performed. Results:(i) Rats treated with only malathion exhibited increased nitric oxide and lipid peroxidation(malondialdehyde) accompanied with a decrease in GSH content, and PON-1 activity in brain and liver. Glutathione peroxidase activity, TAC, glucose concentrations, ACh E and BCh E activities were decreased in brain. There were also raised liver aspartate aminotransferase(AST) and alanine aminotransferase(ALT) activities and increased DNA damage of peripheral blood lymphocytes(Comet assay). Malathion caused marked histopathological changes and increased the expression of iNOS in brain and liver tissues.(ii) In brain of malathion-intoxicated rats, L-NAME or 7-NI resulted in decreased nitrite and MDA contents while increasing TAC and PON1 activity. Reduced GSH and GPx activity showed an increase by L-NAME. ACh E activity increased by 20 mg/kg L-NAME and 10 mg/kg 7-NI. ACh E activity decreased by the higher dose of 7-NI while either dose of 7-NI resulted in decreased BCh E activity.(iii) In liver of malathion-intoxicated rats, decreased MDA content was observed after L-NAME or 7-NI. Nitrite level was unchanged by L-NAME but increased after 7-NI which also resulted in decreased GSH concentration and PON1 activity. Either inhibitor resulted in decreased liver ALT activity.(iv) DNA damage of peripheral blood lymphocytes was markedly inhibited by L-NAME or 7-NI treatment.(v) iNOS expression in brain and liver decreased by L-NAME or 7-NI.(vi) More marked improvement of the histopathological alterations induced by malathion in brain and liver was observed after 7-NI compared with L-NAME. Conclusions: In malathion intoxicated rats, the neuronal NOS inhibitor 7-NI and to much less extent L-NAME were able to protect the brain and liver tissue integrity along with improvement in oxidative stress parameters. The decrease in DNA damage of peripheral blood lymphocytes by NOS inhibitors also suggests the involvement of nitric oxide in this process.     

Role of nitric oxide in the NKCC2 hyperactivity of Dahl "salt-sensitive" rats

Renal NaCl reabsorption is increased in Dahl "salt-sensitive" (DS) rats, due to an increased activity of the Na-K-Cl cotransporter NKCC2. On the other hand, nitric oxide (NO) is an inhibitor of NKCC2 and a deficient nitric oxide synthase (NOS) seems to play an important role in salt-sensitivity of DS rats. Here, we investigated the hypothesis that NKCC2 hyperactivity in DS rats is due to a deficient NOS, via the interactions cyclic GMP (cGMP)/cyclic AMP (cAMP) at the level of the thick ascending Henle's loop (TAL). DS rats DS (males, 250-300 g) and their normotensive controls DR ("salt-resistant") are sacrificed, the kidneys removed and NKCC2 activity is measured in medullary TAL (mTAL) as previously described. Medullary contents of NO are measured with a NitroFlux analyser by heat-reduction of nitrates and nitrites to NO. AMPc levels in mTAL are measured by an EIA immunotest. Neither L-NAME (3 mM), nor L-arginine were able to modify NKCC2 activity in mTAL from DS (pre-hypertensive) or DR rats. Levels of NO in the medullary interstitium and AMPc in mTAL were not significantly different between DS and DR rats. Conversely, in DS rats charged with 2% salt (in the food) during 7 weeks, L-arginine significantly inhibited NKCC2 in DS (35.6 +/- 6.8 vs 25.3 +/- 4.9 nmoles/mg protein/min; p<0.05 non-paired Student's t-test), but not in DR rats. In conclusion, NKCC2 in our mTAL preparation of prehypertensive DS and DR rats is insensitive to L-NAME and L-arginine. This suggests the absence of a functional NOS. NKCC2 hyperactivity of prehypertensive DS is therefore not due to a deficient NOS. This was confirmed by the normal levels of interstitial NO and mTAL cAMP in prehypertensive DS rats. Finally, a salt-load seems to induce NOS expression in mTAL of DS rats. This last observation deserves further investigation.