硅对大鼠血清一氧化氮合酶及一氧化氮的影响

目的　观察硅 ( Na2 Si O3)对血清中一氧化氮合酶 ( NOS)及一氧化氮 ( NO)浓度的影响 ,探讨其抗动脉粥样硬化 ( AS)的作用。方法　高脂饮食饲养 SD大白鼠造成高脂血症和早期 AS模型 ,造模时以 Na2 Si O3 溶液灌胃 ,1 0 w后比较各组血清中 NOS活性和 NO浓度以及动脉壁形态。结果　与正常对照组比较 ,早期 AS时大鼠血清 NOS活性下降 (分别为 2 9.2 3± 1 .837和 2 7.4 3± 2 .0 0 U/ml,P<0 .0 5) ,NO总浓度增加 (分别为35.71± 1 4.4 7和 1 90 .57± 76 .4 3μmol/L ,P<0 .0 1 )。灌胃 Na2 Si O3 溶液 ( 1 0 mg/k g.d )后 NOS及 NO总浓度均恢复到正常组水平。结论　 Na2 Si O3可调节动脉硬化大鼠体内 NO代谢 ,发挥抗 AS作用     

奥曲肽对实验性急性坏死性胰腺炎大鼠肿瘤坏死因子α和一氧化氮的作用

目的探讨急性坏死性胰腺炎(ANP)大鼠肿瘤坏死因子α(TNFα)和一氧化氮(NO)含量的变化及奥曲肽的治疗作用。方法30只SD大鼠随机分为三组,即ANP生理盐水处理组(ANP+NS组)、ANP奥曲肽治疗组(ANP+奥曲肽组)和假手术组(SO组)。测定血清TNFα和NO2－/NO3－量的变化,并于光镜及电镜下观察胰、肺组织标本。结果ANP+NS组血清TNFα和NO2－/NO3－分别为623.5±100.4pg/mL和99.9±28.6μmol/L,明显高于ANP+奥曲肽组(143.1±38.2pg/mL和59.2±26.2μmol/L)及假手术组(2.0±2.7pg/mL和39.2±6.2μmol/L),(P＜0.05)。ANP+NS组大鼠的胰、肺严重受损、而ANP+奥曲肽组大鼠的胰、肺受损程度较轻。结论奥曲肽对ANP大鼠的胰、肺损伤具有保护作用,其机制可能与抑制循环中TNFα和NO水平的增高有关。     

促红细胞生成素对大鼠心肌缺血损伤的保护作用

目的探讨促红细胞生成素(EPO)在大鼠心肌缺血过程中的保护作用及其可能机制。方法建立大鼠心肌缺血模型。将雄性Wistar大鼠60只随机分为治疗组(n=30)和对照组(n=30)。比较24、48 h及1周后血清肌钙蛋白(cTnI)及心肌组织丙二醛(MDA)含量的变化;TFC染色法测定心肌梗死面积;电镜观察心肌超微结构的变化。结果 EPO治疗组大鼠于24、48 h及1周的cTnI水平分别为(10.05±0.81) μg/L、(8.67±0.63) μg/L和(1.36±0.59)μg/L,而对照组相应时间的cTnI水平分别为(11.87±1.19)μg/L、(10.12±0.78)μg/L,和(2.34±0.65)μg/L,差异有统计学意义(P<0.05)。治疗组大鼠心肌组织MDA含量在24、48 h和1周时分别为(1.56±0.09)nmol/L、(1.34±0.18)nmol/L和(1.12±0.10)nmol/L,而对照组心肌组织存相对应时间的MI)A含量分别为(2.02±0.14)nmol/L、(1.84±0.20)nmol/L和(1.61±0.11)nmol/L,差异有统计学意义(P<0.05)。EPO治疗组大鼠于24、48 h及1周的心肌梗死面积(心肌梗死面积/心室肌总面积)分别为30.33%±2.02%、26.25%±3.81%和27.18%±5.15%,而对照组相应时间的心肌梗死面积比例分别为41.11%±1.65%、36.25%±1.85%和38.58%±3.09%,治疗组的心肌梗死面积明显减小,与对照组相比,差异有统计学意义(P均<0.05)。结论 EPO对大鼠心肌急性缺血损伤有明显的保护作用,其机制可能与减轻氧自由基及钙超载损害有关。     

肝硬化伴自发性细菌性腹膜炎患者一氧化氮长期持续过量产生

在严重肝功能衰竭的肝硬化患者中发生的高感染并发症提示有可能经诱生型NO合成酶(iNOS)而使NO产生增多,NO有助于血液动力学紊乱的维持。为了验证这一设想,研究了肝硬化伴自发性细菌性腹膜炎或其他感染及临床状况稳定的患者血清和腹水的硝酸盐水平。 病人与方法:51例酒精性肝硬化患者(男35、女16,年龄34～81岁)分为4组。1组14人为自发性细菌性腹膜炎(SBP);2组11人为菌血症;3组11人尿路感染;4组20人临床状况稳定。4组病人Pugh评分没有差别。 结果与讨论:第4组84份标本的血清硝酸盐水平均为31±2μmol/L。腹水细胞细菌学检查结果阳性之日,1、2、3组平均血清硝酸盐水平分别为(75±17)μmol/L(17份标本)、(63±9)μmol/L(11份标本)和(36±9)μmol/L(11份标     

胸腹水凝血抑制物的检测及其临床意义

目的　探讨三组疾病胸腹水凝血抑制物的水平及其鉴别诊断意义。方法　组织因子途径抑制物 (TFPI)、凝血酶调节蛋白 (TM )和蛋白C(PC)采用ELISA法测定抗原浓度 ,抗凝血酶Ⅲ(ATⅢ )和肝素辅因子Ⅱ (HCⅡ )采用发色底物法测定活性量。结果　结核病组胸腹水TFPI和PC水平分别为 (3 5 .2 5± 13 .61) μg/L和 (4 6.97%± 2 3 .64 % )、恶性肿瘤组分别为 (3 4.10± 14 .97) μg/L和 (3 7.13 %± 2 3 .19% ) ,明显高于肝硬化组的 (7.84± 5 .45 ) μg/L和 (7.90 %± 4.63 % ) (P <0 .0 1)。ATⅢ肝硬化组 (4 9.5 3 %± 2 4.14 % )明显高于结核病组 (3 1.44 %± 2 0 .72 % ) (P <0 .0 5 )。HCⅡ肝硬化组 (91.5 4%± 9.3 1% )和恶性肿瘤组 (88.80 %± 9.2 4% )均明显高于结核病组 (76.5 7%±11.12 % ) (P <0 .0 1)。恶性肿瘤组TM (5 5 .87± 3 7.16) μg/L高于结核病组 (3 6.76± 18.80 ) μg/L ,结核病组又高于肝硬化组 (12 .2 9± 8.5 2 ) μg/L(P <0 .0 1)。在恶性肿瘤组的 5项凝血抑制物指标中 ,TFPⅠ、ATⅢ和TM三项指标在胸腹水脱落细胞阳性组与阴性组间有明显差异 (P <0 .0 5 )。结论　联合检测多项凝血抑制物有助于不同胸腹水疾病的鉴别 ,了解凝血抑制物与胸腹水病理之间的关系     

维生素E对糖尿病大鼠肾脏的保护作用

目的探讨维生素E对糖尿病大鼠肾脏保护作用及其可能机制。方法实验动物分为正常对照组、链脲佐菌素诱导的糖尿病未治疗组、糖尿病给予维生素E（20mg.kg-1.d-1）治疗组,共观察8周。测定尿白蛋白排泄量(UAE),内生肌酐清除率（Ccr）、血浆及肾脏组织一氧化氮（NO）、一氧化氮合成酶（NOS）、内皮素（ET）和肾小球蛋白激酶C（PKC）。结果2周时糖尿病未治疗组Ccr［(6.47±1.51)ml·min-1·kg-1］、尿白蛋白排泄量［(15.60±1.64)μg/24h］、NO［(37.30±3.77)μmol/L］、NOS［(34.89±3.83)U/L］及肾小球细胞膜PKC［(86.85±11.37)pmol·min-1·mgprotein-1］明显高于对照组,ET低于对照组。8周时糖尿病大鼠肾小球细胞膜PKC［(84.18±12.14)pmol·min-1·mgprotein-1］仍明显高于对照组,但NO［(22.75±2.89)μmol/L］及NOS［(21.34±1.92)U/L］低于对照组,ET高于对照组。给予维生素E治疗组8周时,Ccr［(4.46±0.49)ml·min-1·kg-1］及尿白蛋白量［(16.31±1.12)μg/24h］显著低于未治疗组,8周时肾小球细胞膜PKC［(65.19±8.83)pmol·min-1·mgprotein-1］,2周时NO［(33.13±3.77)μmol/L］及NOS［(30.16±2.89)U/L］明显低于未治疗组,维生素E治疗组2周时与8周时的NO及NOS下降幅度明显小于未治疗组。结论维生素E通过抑制蛋白激酶C可以纠正糖尿病早期的肾脏高滤过、高灌注,并与抑制肾脏NO合成有关,抑制蛋白激酶C活性对糖尿病肾病防治尤为重要。     

氯氮平治疗对以阳性或阴性症状为主的精神分裂症患者血清一氧化氮含量的影响

阳性症状为主组32例(阳性组),阴性症状为主组30例(阴性组),单用氯氮平12.5～50.0mg/d,2周内达规定剂量300.0mg/d,共观察8周。治疗前阳性组、阴性组和健康组(28例)血清NO含量分别为(59±16)、(26±7)和(38±11)μmol/L(硝酸还原酶法),组间比较均P<0.01。治疗后阳性组血清NO降至(39±8)μmol/L,阴性组升至(32±8)μmol/L,     

双氢青蒿素对卡氏肺孢子虫肺炎大鼠NO水平的影响

目的　研究双氢青蒿素对卡氏肺孢子虫肺炎大鼠血清和肺泡巨噬细胞上清液 NO水平的影响。　方法　以醋酸可的松皮下注射 Wistar大鼠建立卡氏肺孢子虫肺炎动物模型 ,用 6 0 mg/ kg双氢青蒿素治疗实验大鼠 ,杀鼠取肺 ,用胶原酶消化法分离肺泡巨噬细胞 ,用 L PS刺激培养 72 h,同时设有感染组和正常对照。用 NO试剂盒分别检测大鼠血清和肺泡巨噬细胞上清液 NO活性。　结果　感染组大鼠血清、肺泡巨噬细胞上清液原液以及经 L PS刺激后肺泡巨噬细胞上清液 NO浓度分别为 ( 16 7.3± 2 3.1)、( 141.6± 18.0 )和 ( 12 9.5± 2 8.4) μmol/ L,治疗组分别为 ( 111.8± 40 .6 )、( 136 .3± 35 .1)和 ( 12 9.9± 14.2 ) μmol/ L,正常对照组分别为 ( 87.2± 32 .1)、( 10 9.8± 18.0 )和 ( 136 .2± 30 .5 ) μmol/ L,可见感染组和治疗组大鼠 NO水平均高于相应的正常对照 ,治疗组 NO水平低于相应的感染组。　结论　卡氏肺孢子虫感染可能引起大鼠肺泡巨噬细胞分泌高水平 NO,经双氢青蒿素治疗后 ,PCP大鼠肺泡巨噬细胞分泌 NO水平降低。     

枳实对急性冠脉综合征病人血管内皮功能及血小板活化的影响

目的 探讨枳实对急性冠脉综合征(ACS)病人血小板活化及血管内皮功能的影响.方法 67例急性冠脉综合征病人随机分成枳实组(n=34)、常规组(n=33).所有病人分别于入院时及用药3周后取血行血小板胞质内α-颗粒膜糖蛋白(CD62p)、血清一氧化氮(NO)、血浆内皮素-1(ET-1)测定.另选本院同期健康体检者30名作为正常组,要求采血前两周内未服用任何药物.结果 治疗后枳实组与常规组NO水平分别为(20.63±5.80)μmol/L、(16.25±5.14)μmol/L,显著低于正常组的(30.79±3.28)μmol/L(P＜0.01),ET-1与CD62p水平分别为(49.56±13.07)pg/mL、(60.61±10.49)pg/mL与18.74%±8.68%、18.98%±4.58%,明显高于正常组的(33 98±7.41)pg/mL、11.85%±2.67%(P＜0.01).治疗3周后两病例组血清NO水平显著升高、血浆ET-1水平明显降低,枳实组效果显著优于常规组(P＜0.01),但两组的NO、ET-1水平与正常组仍有统计学意义(P＜0.01);CD62p两组治疗后较治疗前均明显降低(P＜0.01),治疗后两组无统计学意义(P＞0.05).结论 枳实能够改善急性冠脉综合征病人内皮功能,而对血小板活化无明显影响.     

不同剂量氟伐他汀对急性冠状动脉综合征患者血管内皮功能及炎症因子的影响

目的探讨较大剂量与常规剂量氟伐他汀相比,对急性冠脉综合征(ACS)患者是否有进一步的改善血管内皮功能和抗炎的作用。方法收集本院ACS患者120例,常规治疗基础上随机给予氟伐他汀40mg(40mg组)或氟伐他汀80 mg(80 mg组),每晚睡前服用。治疗4周,测定治疗前后患者血清NO、Hs-CRP、IL-6、HSP60的水平,随访临床事件发生情况。结果两组患者治疗4周后血清NO水平均有所升高[40 mg组:(56.68±12.01)μmol/L比(74.49±12.38)μmol/L,P<0.05;80mg组:(51.29±14.67)μmol/L比(82.57±12.17)μmol/L,P<0.01],且80 mg组患者血清NO水平升高更明显(P<0.05)。两组患者血清Hs-CRP、IL-6、HSP60水平均有所下降[40mg组分别为:(14.79±12.68)mg/L比(6.17±4.68)mg/L,(47.96±37.54)ng/L比(36.21±20.06)ng/L,(6.36±1.24)μg/L比(3.14±1.09)μg/L,P<0.05;80 mg组分别为:(14.48±12.32)mg/L比(4.31±3.56)mg/L,(50.35±40.17)ng/L比(31.24±15.49)ng/L,(6.25±1.16)μg/L比(1.25±0.98)μg/L,P<0.01],且80mg组下降更明显(均为P<0.05)。临床事件的随访观察显示,40 mg组共有10例(16.67%)患者发生心血管事件,80 mg组仅有4例(6.67%)发生心血管事件,发生率两组间差异有统计学意义(P<0.05)。结论氟伐他汀可升高ACS患者血清NO水平,降低Hs-CRP、IL-6及HSP60水平,其改善血管内皮功能和抗炎作用在短期内呈剂量依赖性。较大剂量氟伐他汀早期强化治疗可以明显减少ACS患者近期心血管事件的发生率,且安全性良好。     

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.     

Gender differences in hepatic ischemic reperfusion injury in rats are associated with endothelial cell nitric oxide synthase-derived nitric oxide

AIM: This study was designed to examine the hypothesis that gender differences in I/R injury are associated with endothelial cell nitric oxide synthase (eNOS)-derived nitric oxide (NO). METHODS: Wistar rats were randomized into seven experimental groups (12 animals per group). Except for the sham operated groups, all rats were subjected to total liver ischemia for 40 min followed by reperfusion. All experimental groups received different treatments 45 min before the laparotomy. For each group, half of the animals (six) were used to investigate the survival; blood samples and liver tissues were obtained in the remaining six animals after 3 h of reperfusion to assess serum NO, alanine aminotransferase (ALT) and TNF-α levels, liver tissue malondialdehyde (MDA) content, and severity of hepatic I/R injury. RESULTS: Basal serum NO levels in female sham operated (FS) group were nearly 1.5-fold of male sham operated (MS) group (66.7±11.0 μmol/L vs45.3μ10.1 μmol/L, P<0.01). Although serum NO levels decreased significantly after hepatic I/R (P<0.01, vs sham operated groups), they were still significantly higher in female rat (F) group than in male rat (M) group (47.8±8.6 μmol/L vs 23.8±4.7 μmol/L, P<0.01). Serum ALT and TNF-α levels, and liver tissue MDA content were significantly lower in F group than in M group (370.5±46.4 U/L, 0.99±0.11 μg/L and 0.57±0.10 μmol/g vs668.7±78.7 U/L, 1.71±0.18μg/L and 0.86±0.11 μmol/g, respectively, P<0.01). I/R induced significant injury to the liver both in M and F groups (P<0.01 vs sham operated groups). But the degree of hepatocyte injury was significantly milder in F group than in M group (P<0.05 and P<0.01). The median survival time was six days in F group and one day in M group. The overall survival rate was significantly higher in F group than in M group (P<0.05). When compared with male rats pretreated with saline (M group), pretreatment of male rats with 17-β-estradiol (E2) (M+E2 group) significantly increased serum NO levels and significantly decreased serum ALT and TNF-α levels, and liver tissue MDA content after I/R (P<0.01). The degree of hepatocyte injury was significantly decreased and the overall survival rate was significantly improved in M+E2 group than in M group (P<0.01 and P<0.05). The NOS inhibitor Nw-nitro-L-arginine methyl ester (L-NAME) treatment could completely abolish the protective effects of estrogen in both male and female rats. CONCLUSION: The protective effects afforded to female rats subjected to hepatic I/R are associated with eNOS-derived NO.     

Mesenteric vasodilator responses in cirrhotic rats: A role for nitric oxide

The contribution of nitric oxide to mesenteric arterial vasodilator responses was investigated in the isolated perfused mesenteric arterial bed of cirrhotic rats (carbon tetrachloride/phenobarbitone; n = 6). Age- matched (n = 9) and phenobarbitone-treated rats (n = 9) served as controls. Responses to the endothelium-dependent dilators acetylcholine and adenosine 5'-triphosphate (ATP) and the smooth muscle dilator (NO donor) sodium nitroprusside were investigated after tone was raised by continuous infusion of methoxamine, before and during infusion of the NO synthesis inhibitor N^G-nitro-L-arginine methyl ester (L-NAME; 30 mumol/L) +/- L-arginine (1 mmol/L). A significant hyporesponsiveness to methoxamine infusion in cirrhotic preparations (P < .05) was not fully corrected by L-NAME. There was no difference in the percentage vasodilator response to acetylcholine in the cirrhotic group compared with controls; L-NAME significantly and reversibly inhibited the dilator response in all groups. ATP elicited dose-dependent vasodilation that, in the absence of L-NAME, did not differ between the groups. By contrast, in the presence of L-NAME, ATP (5 x 10^-8 mol) produced pronounced, reversible vasoconstriction only in cirrhotic animals (P < .02). Vasodilatation attributable to sodium nitroprusside (5 x 10^-8 mol) was significantly attenuated in cirrhotic rats. The methoxamine data support the concept of mesenteric hyposensitivity to vasoconstrictor agents in cirrhosis that may be at least partly NO mediated. Increased NO activity in smooth muscle leading to decreased guanylate cyclase availability may account for the diminished vasodilator responses to sodium nitroprusside in cirrhotic preparations. The unchanged responsiveness to vasodilatation by acetylcholine (ACh) and the vasoconstriction to ATP observed during NO blockade in cirrhotic animals indicate that mesenteric endothelial NO is unchanged or possibly diminished. (Hepatology 1996 Jan;23(1):130-6)     

Contribution of nitric oxide to the pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated rats

BACKGROUND & AIMS: Decreased cardiac contractility and beta-adrenergic responsiveness have been observed in cirrhosis, but the etiology remains unclear. We aimed to test the role of nitric oxide (NO), a negative inotropic agent, in the pathogenesis of cirrhotic cardiomyopathy in a rat model. METHODS: Cirrhosis was induced by bile duct ligation. Four weeks after ligation or sham operation, cardiac levels of tumor necrosis factor (TNF)-alpha, guanosine 3,5'-cyclic monophosphate (cGMP), inducible NOS (NOS2), and endothelial constitutive NOS (NOS3) messenger RNA (mRNA) and protein were determined. Serum nitrite/nitrate level was measured. Cardiac contractile function was evaluated in isolated left ventricular papillary muscles in the absence and presence of the NOS inhibitor nitro-L-arginine methyl ester (L-NAME). RESULTS: Cardiac TNF-alpha, NOS2 mRNA and protein, cGMP, and serum interleukin (IL)-1beta and nitrite/nitrate levels were significantly higher in cirrhotic rats than sham controls. No significant differences in NOS3 mRNA or protein were found between cirrhotic and sham control rats. Baseline isoproterenol-stimulated papillary muscle contractile force was significantly lower in the cirrhotic group; with L-NAME incubation, contractile force increased significantly in cirrhotic rats but was unaffected in the controls. In normal papillary muscles, IL-1beta attenuated the contractility, but coincubation with L-NAME again reversed this attenuation. Incubation with the exogenous NO donor S-nitroso-N-acetyl-penicillamine also blunted papillary muscle contractility. CONCLUSIONS: These results suggest that cytokine-induced stimulation of NOS2 plays a significant role in the pathogenesis of cirrhotic cardiomyopathy.     

Effects of nitric oxide synthesis inhibitor in long-term treatment onhyperdynamic circulatory state in cirrhotic rats

AIM To investigate the effects of low dosage of nitric oxide synthesis (NOS) inhibitor NG-nitro-L-argininemethyl ester (L-NAME) in long-term treatment on hyperdynamic circulatory state in rats with cirrhosis.METHODS Cirrhosis model was induced in male SD rats by injection of 60% CC14 oily solutionsubcutaneously. Cirrhotic rats were treated with L-NAME (0.5 mg·kg-1·d-1) by gavage for two weeks. Meanarterial pressure (MAP), cardiac output (CO), cardiac index (CI), splanchnic vascular resistance (SVR),splanchnic blood flow (SBF) and serum NO levels were determinded in L-NAME-treated, L-NAME-untreated cirrhotic rats and controls by using 57Co-Labled microsphere technique and a fluorometric assay,respectively.RESULTS Untreated cirrhotic rats had significantly lower MAP, SVR and higher PP, CO, CI, SBF andNO concentration than controls ( 14.42±0,47 kPa vs 17.05±0.34 kPa, 2.974±0.186 kPa·mL-1·min-1 vs4.234±0.118 kPa·mL-1·min-1, 1.665±0.067 kPa vs 1.123±0.096 kPa, 189.99±9.26 mL/min vs 135.5±3.55 mL/min, 55.89±1.82 mL-1·min-1·100g-1 BW vs 39.68±1.64 mL-1·min-1·100g-1 BW, 4.60±1.25μmol/L vs 0.53±0.26 μmol/L, P<0.01, respectively). In treated cirrhotic rats, L-NAME significantlyattenuated the increase of CO, CI, SBF, NO concentration and the decrease of MAP and SVR. In treatedcirrhotic rats, L-NAME induced a marked decrement of NO concentration than untreated cirrhotic rats(1.471 ±0.907 μmol/L vs 4.204±1.253 μmol/L, P<0.01).CONCLUSION The endogenous NO may play an important role in the changes of hemodynamics pattern incirrhosis,and hyperdynamic circulatory state in rats with cirrhosis can be ameliorated by long-term low doseL-NAME treatment.     

Antihypertensive Agents Prevent Nephrosclerosis and Left Ventricular Hypertrophy Induced in Rats by Prolonged Inhibition of Nitric Oxide Synthesis

We investigated the ability of the angiotensin converting enzyme (ACE) inhibitor imidapril hydrochloride, and of the calcium channel blocker amlodipine besilate, to prevent nephrosclerosis and left ventricular hypertrophy (LVH) in rats with hypertension induced by chronic inhibition of nitric oxide (NO). Male Wistar rats were given distilled water (control), N^G-nitro- -arginine methyl ester (L-NAME) 500 mg/L, L-NAME plus imidapril 10 mg/L or 100 mg/L, or L-NAME plus amlodipine 50 mg/L or 100 mg/L in the drinking water (n = 10–12). We then collected 24-h urine samples at 2, 4, and 6 weeks, obtained blood samples at 6 weeks, and histologically examined the kidney and heart. L-NAME markedly reduced the levels of NO metabolites in serum and urine while increasing the tail-cuff blood pressure, the urinary albumin level (1.90 + 0.65 v 0.05 + 0.02 mg/day/100 g in control), and the area of the left ventricular wall (83.3 + 3.0 v 69.8 + 1.8 mm² in control). Nephrosclerosis and myocardial interstitial fibrosis were documented histologically. The plasma renin activity was significantly higher in rats treated with L-NAME than in the control rats. The concomitant administration of imidapril (10 mg/L) with L-NAME completely normalized the tail-cuff pressure, the LVH (70.8 + 1.8 mm²), the albuminuria (0.05 + 0.01 mg/day/100 g), and the histologic changes. Amlodipine (50 mg/L) also ameliorated the L-NAME–induced effects, but to a lesser extent. Thus, the chronic inhibition of NO synthesis in rats produced nephrosclerosis and LVH that were effectively prevented by giving imidapril at a dose lower than that of amlodipine. We conclude that ACE inhibitors can prevent nephrosclerosis and LVH even in the presence of a reduction in NO production, implying that in rats the inhibition of the renin-angiotensin system is more effective than the blockade of calcium channels in preventing hypertensive tissue injury.     

Potential effects of L-NAME on alcohol-induced oxidative stress

AIM: Nitric oxide (NO) is a highly reactive oxidant synthesized from L-arginine by nitric oxide synthase (NOS). NO may cause injury through the generation of potent radicals. Nw-nitro-L-arginine methyl ester (L-NAME) is a non-selective inhibitor of NOS. We aimed to evaluate whether L-NAME treatment had protective effects against oxidative stress in rats intragastrically fed with ethanol during a 4 wk-period. METHODS: Thirty-six male Wistar rats were divided into 3 equal groups: group 1 (control group-isocaloric dextrose was given), group 2 (6 g/kg·d ethanol-induced group) and group 3 (both ethanol 6 g/kg·d and L-NAME 500 mg/L in drinking water-given group). Animals were sacrificed at the end of 4 wk-experimental period, and intracardiac blood and liver tissues were obtained. Biochemical measurements were performed both in plasma and in homogenized liver tissues. Alanine amino transferase (ALT), aspartate amino transferase (AST), malondialdehyde (MDA), NO, superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels were measured by spectrophotometry. RESULTS: ALT and AST in group 2 (62 U/L and 128 U/L, respectively) were higher than those in group 1 (24 U/L and 38 U/L) and group 3 (37 U/L and 81 U/L) (P<0.001 for both). Plasma and tissue levels of MDA in group 2 (4.66 μmol/L and 0.55 μmol/mg protein) were higher than in group 1 (2.65 μmol/L and 0.34 nmol/mg protein) and group 3 (3.43 μmol/L and 0.36 nmol/mg protein) (P<0.001 for both). Plasma and liver tissue levels of NO in group 2 (54.67 μmol/L and 586.50 nmol/mg protein) were higher than in group 1 (34.67 μmol/L and 435.33 nmol/mg protein) and group 3 (27.50 μmool/L and 412.75 nmol/mg protein ) (P<0.001 for both). Plasma and liver tissue SOD activities in group 2 (15.25 U/mL and 5.38 U/ mg protein, respectively) were lower than in group 1 (20.00 U/mL and 8.13 U/ mg protein) and group 3 (19.00 U/mL and 6.93 U/ mg protein) (P<0.001 for both). Plasma and liver tissue CAT activities in group 2 (145 U/mL and 37 U/ mg protein, respectively) were lower than in group 1 (176 U/mL and 73 U/mg protein) and group 3 (167 U/mL and 61 U/mg protein) (P<0.001 for both). Meanwhile, erythrocytes and liver tissue levels of GSH in group 2 (4.12 mg/g Hb and 5.38 nmol/mg protein, respectively) were lower than in group 1 (5.52 mg/g Hb and 4.49 nmol/mg protein) and group 3 (5.64 mg/g Hb and 4.18 nmol/mg protein) (P<0.001 for both). CONCLUSION: Our findings show that L-NAME may produce a restorative effect on ethanol-induced liver damage via decreasing oxidative stress and increasing antioxidant status.     

Renal effects of the chronic inhibition of nitric oxide synthesis in cirrhotic rats with ascites

Previous studies have shown that acute inhibition of nitric oxide (NO) synthesis improves sodium and water excretion and increases blood pressure in cirrhotic rats with ascites, thus suggesting that NO is an important factor contributing to the arterial hypotension and sodium retention of liver cirrhosis. In the present work we have analyzed the renal effects derived from the chronic oral treatment (10 days) with aminoguanidine (AG, 100 mg/kg/day), a preferential inhibitor of inducible NO synthase (iNOS), or Nw-Nitro-L-Arginine Methyl Ester (L-NAME, 0.5 mg/kg/day), a nonselective inhibitor of NOS, in an experimental model of liver cirrhosis with ascites (carbon tetrachloride inhalation). Untreated cirrhotic rats showed lower mean arterial pressure (MAP), diuresis, natriuresis and glomerular filtration rate (GFR) and similar renal blood flow (RBF) compared with the untreated control rats. Chronic administration of AG did not modify significantly any parameter in cirrhotic and control animals. Conversely, long-term L-NAME administration to cirrhotic rats normalized MAP and significantly increased water and sodium excretion, whereas in control animals these parameters were not significantly modified. These results show that chronic NO synthesis inhibition with L-NAME, but not with aminoguanidine, improves renal perfusion pressure and increases the lower sodium and water excretion of cirrhotic rats with ascites. Thus, an enhanced production of NO is an important factor contributing to the renal sodium and water retention characteristic of liver cirrhosis.     

Interaction between beta-adrenergic receptor stimulation and nitric oxide release on tissue perfusion and metabolism

Nitric oxide (NO) may be an important modulator of sympathetic tone. We used im and sc microdialysis in humans to characterize the interaction of NO synthase inhibition and adrenoreceptor stimulation on tissue perfusion, metabolism, and norepinephrine release. Microdialysis probes were perfused with L- or D-nitro-L-arginine-methyl-ester (100 micromol/L) followed by incremental doses of isoproterenol, epinephrine, or nitroprusside. Blood flow was estimated based on the ethanol dilution technique. In muscle, the increase in blood flow with isoproterenol was abolished by L-NAME. The ethanol ratio was 0.03 +/- 0.011 with D-NAME and 0.075 +/- 0.014 with L-NAME during isoproterenol treatment (1 micromol/L). The effect was less pronounced in adipose tissue. The vasodilatory effect of nitroprusside was similar with D- and L-NAME. L-NAME augmented isoproterenol- and epinephrine-induced glycerol release. Dialysate glycerol during 1 micromol/L isoproterenol was 47 +/- 6.7 micromol/L with D-NAME and 72 +/- 15 micromol/L with L-NAME. In skeletal muscle, dialysate norepinephrine during 1 micromol/L isoproterenol treatment was 0.73 +/- 0.17 and 1.3 +/- 0.15 nmol/L with D- and L-NAME, respectively. We conclude that NO synthase inhibition attenuates beta(2)-adrenoreceptor-mediated vasodilation and enhances beta-adrenoreceptor-mediated lipolysis. These effects are in part mediated through an increase in interstitial norepinephrine concentrations. The data are consistent with the idea that in humans, NO is important in modulating and ameliorating sympathetic effects in peripheral tissues.     

微卡对致敏小鼠气道炎症和Th1/Th2比例变化的影响

目的　观察母牛分支杆菌菌苗 (微卡 )对致敏小鼠抗原攻击后气道炎症、Th1和Th2细胞因子的比例变化 ,评估微卡防治哮喘的药理作用。方法　小鼠分 9组 ,每组 7～ 1 0只。采用皮肤划痕、气管滴入、肌肉注射三种给药途径单次给药 ,观察比较微卡菌苗对致敏小鼠吸入抗原后支气管肺泡灌洗液 (BALF)中炎症细胞 ,γ干扰素 (IFN γ)和白细胞介素 4(IL 4)水平变化的影响和作用强度。结果　经皮肤划痕 (2 .2 5μg)、气管内滴入 (2 .2 5μg)、肌肉注射 (2 2 .5μg)后BALF中炎症细胞总数分别为 (6± 6)× 1 0 8/L、(7± 6)× 1 0 8/L、(8± 5)× 1 0 8/ml,与模型组 (1 5± 8)× 1 0 8/L比较 (P <0 .0 5) ;嗜酸细胞 :皮肤划痕组 (2 2 5μg)为 0 7± 0 5、气管内滴入 (2 2 5μg)为 1 6± 1 9、肌肉注射 (7 5μg)为 2 6±1 3、肌肉注射组 (2 2 .5μg)为 1 .40± 1 .2 0 ,与模型组 (4.90± 4 .60 )比较 (P <0 .0 5或 <0 .0 1 ) ;皮肤划痕组 (2 .2 5μg)BALF中IFN γ水平为 (2 89± 57)pg/ml、气管滴入组 (2 .2 5μg)为 (335± 57)pg/ml、肌肉注射组 (2 2 .5μg)为 (31 3± 49)pg/ml,与模型组 (2 1 6± 42 )pg/ml比较 (P <0 .0 5或 0 .0 1 ) ;皮肤划痕组(2 .2 5μg) BALF中IL 4水平为 (63± 1 9)pg/ml、气管滴入组