新生儿缺氧缺血性脑病血浆一氧化氮及一氧化氮合成酶水平对预后判断的意义

目的探讨新生儿缺氧缺血性脑病 (hypoxic-ischemic encephalopathy , HIE)时一氧化氮、一氧化氮合成酶 (Nitrogen monoxide synthase , NOS)水平的变化及其对预后判断及恢复期指导的意义. 方法 采用比色等方法测定 32例 HIE患儿及 30例正常新生儿血浆一氧化氮、一氧化氮合成酶活性水平. 结果 正常对照组一氧化氮、 NOS水平分别为 (72.84± 12.35) μ mol/L和 (0.203± 0.05) kU/g, HIE组为 (129.80± 32.66) μ mol/L和 (0.352± 0.124) kU/g;其中轻度 HIE为 (105.65± 36.30) μ mol/L和 (0.289± 0.09) U/mg;中度 HIE为 (135.03± 24.40) μ mol/L和 (0.325± 0.16) kU/g;重度 HIE组为 (144.55± 26.32) μ mol/L和 (0.364± 0.01) kU/g. HIE急性期一氧化氮、 NOS水平校正常新生儿明显升高 (t=- 8.97, P< 0.01),中、重度 HIE升高更显著 (t=- 10.62,- 12.01,P< 0.01),中、重度 HIE患儿较轻度 HIE患儿升高明显 (t=- 2.12,- 2.92,P< 0.05,P< 0.01).中、重度 HIE之间则无明显差别. 结论一氧化氮、 NOS水平高低与 HIE患儿脑损伤程度和预后有关,可作为判断 HIE患儿病情恢复及预后的指标之一.     

葛根素对急性脑梗死血清一氧化氮、丙二醛、超氧化物歧化酶的作用研究

目的观察葛根素注射液对急性脑梗死患者血清一氧化氮(NO)、一氧化氮合酶(NOS)、丙二醛(MDA)和超氧化物歧化酶(SOD)含量的影响.方法110例急性脑梗死患者随机分为对照组(56例)和治疗组(54例),对照组给予低分子右旋糖酐、维脑路通注射液静滴,治疗组给予葛根素注射液静滴.2组分别于治疗前、治疗第3日和第7日测定NO、NOS、MDA、SOD,并比较2组治疗前后梗死灶体积减少值.结果用药第3日和第7日,治疗组NO、NOS、MDA均低于对照组(P均<0.05),SOD高于对照组(P<0.05);发病后第8日复查颅脑CT,治疗组治疗后梗死灶减少值[平均(24±27)mm3]大于对照组[平均(11±20)mm3,P<0.05].结论葛根素注射液具有抑制急性脑梗死患者脑梗死后诱导产生的大量NO合成和抑制超氧阴离子自由基的作用,可作为脑细胞保护剂治疗急性脑梗死患者.     

计算机辅助认知训练对精神分裂症患者认知功能的康复效果

目的探讨计算机辅助认知训练对精神分裂症患者认知功能康复治疗效果。 方法研究组51例精神分裂症患者，通过计算机辅助认知作业训练治疗2个月，对照组53例精神分裂症患者采用常规工娱疗法治疗2个月。2组患者治疗前后分别进行阳性和阴性症状量表（PANSS）、连线测验A和B、韦氏成人记忆量表（WMS）和威斯康星卡片分类测验（WCST）等神经认知功能测验，并进行统计学分析比较。 结果①治疗后，研究组和对照组患者临床症状PANSS量表总评分［(59.82±8.41)、(59.45±9.05)分］及阴性症状量表的评分［(16.67±3.20)、(17.08±3.23)分］均较组内治疗前［PANSS总评分(70.23±7.62)、(68.32±10.14)分及阴性症状量表评分(21.46±3.26)、(20.82±4.21)分］明显下降，组内差异均有统计学意义（P<0.05）；研究组治疗后上述各项的减分程度略高于对照组，但组间差异无统计学意义（P&rt;0.05）。②治疗后，研究组连线测验A测验成绩［（44.14±17.51）分］和B测验成绩［（96.47±34.43）分］均较组内治疗前［（51.76±21.18）和（114.31±35.76）分］明显下降（P<0.01)；而对照组连线测验A测验成绩和B测验成绩治疗前后变化不大（P&rt;0.05）。③治疗后，研究组WMS再认和WMS再生两个分测验成绩［(8.21±3.96)、(10.24±3.52)分］较组内治疗前［(5.83±3.12)、(8.63±3.45)分］明显增加，差异有统计学意义（P<0.01）；对照组WMS再认和WMS再生两个分测验成绩治疗前后变化不大（P&rt;0.05）；研究组测验成绩提高明显好于对照组（P=0.01）。④治疗后，研究组WCST的总测验数、持续错误数、正确数和分类数成绩［(87.82±23.21)、(23.20±11.5)、(23.14±42.00)、(4.80±0.76)］较组内治疗前［(78.20±21.40)、(28.87±10.21)、(21.54±26.50)、(4.26±0.08)］明显提高（P<0.05）；对照组WCST测验总测验、持续错误数、正确数和分类数成绩治疗前后变化不大（P&rt;0.05）；研究组的测验成绩变化明显大于对照组（P<0.01）。 结论计算机辅助认知训练可以提高精神分裂症患者认知功能测验任务成绩，改善患者部分认知领域的功能。     

氯沙坦对自发性高血压大鼠血管内氧化应激态的影响

目的：探讨氯沙坦对自发性高血压大鼠(spontaneous hypertension rats，SHR)血浆一氧化氮、一氧化氮合酶(nitric oxide synthase，NOS)、超氧化物歧化酶(superoxide dismutase，SOD)和活性氧的影响。方法：30只实验动物分为3组，其中10只Wistar京都大鼠(WKY)为正常血压组，20只SHR随机分为SHR组和使用氯沙坦SHR组。氯沙坦灌胃8周后，取血浆采用化学比色法测定一氧化氮和活性氧的含量及NOS．SOD活性。结果：SHR组与正常血压组比较，血浆活性氧含量和NOS活性显著增高(t=52.15，6.87，P&;lt;0.001)，一氧化氮含量和SOD活性显著降低(t=4.60，6.60，P&;lt;0.001)；氯沙坦SHR组活性氧含量[(864.6&;#177;24.8)kU／L]比SHR组[(2134.8&;#177;87.6)kU／L]显著降低(t=44.11，P&;lt;0.001)，一氧化氮含量增高(t=3.09，P&;lt;0.05)，但SOD和NOS的活性变化，差异无显著性意义(P&;gt;0.05)。结论：高血压可能是血管内氧化应激态形成的重要因素之一，而氯沙     

L精氨酸枕大池注射对兔脑血管痉挛的影响及作用机制

目的 研究 L 精氨酸枕大池注射对兔蛛网膜下腔出血后血管痉挛的影响及作用机制. 方法 采用双侧颈动脉结扎及枕大池二次注血法制造兔蛛网膜下腔出血模型.在蛛网膜下腔出血后第 4天,以比色法测定血清及脑脊液中一氧化氮及脑组织的浓度.光镜下测定基底动脉的动脉壁厚度和基底动脉的内径,以其比值作为脑血管痉挛的指标.治疗组分为 300 μ mol/L及 500 μ mol/L组,在蛛网膜下腔出血后第 4天,枕大池持续微泵滴注 L 精氨酸,在滴注后再分别研究上述指标. 结果 蛛网膜下腔出血后第 4天,基底动脉的动脉壁厚度和内径的比值 (0.085± 0.007)明显升高 (t=20.26,P< 0.05);血清一氧化氮 [(24.34± 7.36) μ mol/L,t=6.72 ,P < 0.05]及脑脊液中一氧化氮 [(10.68± 3.43) μ mol/L,t=4.25,P < 0.05]及脑组织 NOS[(0.007± 0.001) nmol/(s@ g),t=6.14,P < 0.05].的浓度降低.在 L 精氨酸滴注后,脑血管痉挛缓解.血清一氧化氮 [(37.38± 6.42) μ mol/L,t=3.27,P < 0.05]、脑脊液中一氧化氮 [(14.16± 3.36) μ mol/L, t=1.98,P < 0.05]脑组织一氧化氮合酶 (nitric oxygenase, NOS)[(0.011± 0.002) nmol/(s@ g ),t=3.10,P < 0.05]的浓度较对照组明显升高. 结论 L-精氨酸枕大池注射对兔蛛网膜下腔出血后的血管痉挛具有治疗作用. L-精氨酸可能通过影响一氧化氮及 NOS而起作用.     

固本化痰祛瘀法对慢性阻塞性肺疾病缓解期患者血浆一氧化氮及内皮素水平影响的随机对照研究

目的探讨固本化痰祛瘀法对慢性阻塞性肺疾病( chronic obstructive pulmonary disease,COPD)缓解期患者的治疗作用及其对血浆一氧化氮,内皮素水平的影响和意义. 方法将 52例 COPD缓解期患者随机分为治疗组及对照组,观察固本化痰祛瘀汤对 COPD缓解期患者临床症状及血浆一氧化氮,内皮素水平的影响,并与单纯的补益固本汤对照组进行对照研究. 结果两组治疗后临床症状积分均显著下降,并且治疗组的证候积分下降 9.0± 3.6,改善程度明显优于对照组 7.0± 3.2( t=2.036,P< 0.05).与治疗前比较,两组的血浆一氧化氮水平显著上升(治疗组 t=12.02,对照组 t=12.163, P均 < 0.001) ,内皮素水平显著下降(治疗组 t=9.389,P< 0.01,对照组 t=2.801, P< 0.05),而且治疗组 ET水平下降幅度明显大于对照组( t=3.066,P< 0.01). 结论固本化痰祛瘀法对 COPD缓解期的治疗有良好的治疗效果,有一定的保护血管内皮细胞功能,有利于减缓肺动脉高压的形成和发展.     

参麻益智胶囊对痴呆大鼠一氧化氮和一氧化氮合酶的影响

目的:证实参麻益胶囊治疗血管性痴呆的药效以及探讨其作用机制。方法:采用颈内动脉注射同种大鼠微血栓悬液制作大鼠血管痴呆(多发性脑梗死)动物模型,设立参麻益智胶囊高、中、低剂量组和阳性药、模型及正常对照组,连续给药6周后,测定血浆、脑组织的一氧化氮含量及一氧化氮合酶(NOS)活性。结果:①模型对照组大鼠血浆中的一氧化氮含量(71.6±24.3)μmol/L和NOS活性(135.9±35.8)nmol/(L·s)明显高于正常对照组(45.5±17.0)μmol/L和(59.3±32.2)nmol/(L·s),P<0.01。②模型对照组大鼠脑组织中的一氧化氮含量(261.0±30.0)μmol/g和NOS活性(66.8±7.2)nmol/(g·s)明显高于正常对照组(191±39)μmol/g和(52.2±2.8)nmol/(g·s),P<0.05。③参麻益智胶囊高、中、低剂量组大鼠血浆中的一氧化氮含量分别为(52.6±15.3),(56.0±17.9),(56.3±12.3)μmol/L和NOS活性(71.9±31.2),(99.7±26.5),(93.0±35.7)nmol/(L·s)明显低于模型对照组(P<0.01)。④参麻益智胶囊高、中、低剂量组大鼠脑组织中的一氧化氮含量和NOS活性明显低于模型对照组(P<0.01)。结论:参麻益智胶囊可降低血管性痴呆大鼠血浆、脑组织中一氧化氮含量及NOS活性。     

电针对癫痫大鼠脑组织及肝脏的一氧化氮和一氧化氮合酶含量的影响

目的：探讨电针对癫痫大鼠脑组织和肝组织中一氧化氮，一氧化氮合酶(nitric oxide syntheses，NOS)的影响，以及电针治疗癫痫的可能机制。方法：实验于2004-03／10在南京中医药大学第二临床医学院实验室完成。选择SD大鼠40只，随机分成为正常组、模型组、电针组、假针刺组，每组10只。采用比色法测定对癫痫造模大鼠的一氧化氮，NOS和一氧化氮／NOS比值进行随机对照分析性研究。结果：模型组脑一氧化氮[(19．76&;#177;2．66)μmol／L]，NOS[(498．8&;#177;947)nkat／g]和一氧化氮／NOS比值(1．38&;#177;0．46)明显高于正常组(P&;lt;0．05)，电针组脑一氧化氮[(6．04&;#177;3．52)μmol／L]，NOS[(203．9&;#177;102．2)nkat／g]和一氧化氮／NOS比值(1．00&;#177;0．57)明显低于模型组(P&;lt;0．05)，假针刺组一氧化氮，NOS和一氧化氮／NOS含量不明显变化。肝组织中各项因子变化与脑组织中变化一致。结论：电针对癫痫大鼠的一氧化氮，NOS和一氧化氮／NOS有显著的抑制调节作用。这可能是电针治疗癫痫临床取得疗效的重要机制之一。     

妊娠高血压综合征绒毛合体滋养细胞一氧化氮合酶活性的定量研究

目的探讨妊娠高血压综合征(妊高征)、正常妊娠合体滋养细胞一氧化氮合酶(NOS)的活性变化及合体滋养细胞源性的一氧化氮(NO)在妊高征发病中的作用.方法采用NADPH-D组织化学方法显示21例正常妊娠、15例重度妊高征,15例中度妊高征、14例轻度妊高征胎盘绒毛合体滋养细胞NOS活性,运用显微图像分析技术计算出每例胎盘绒毛合体滋养细胞NOS活性反应产物甲月替灰度值.结果中度妊高征(79.9±8.8)、重度妊高征(78.7±8.4)胎盘绒毛合体滋养细胞NOS活性反应产物甲月替灰度值比轻度妊高征(85.6±8.4)及正常足月妊娠(86.8±11.5)低(P<0.05).结论妊高征病人胎盘绒毛合体滋养细胞NOS活性降低,导致其NO生成减少,在妊高症发病中起重要作用.     

川芎嗪拮抗庆大霉素耳毒性作用的实验研究

目的探讨川芎嗪拮抗庆大霉素耳中毒有效。方法采用脑干听觉诱发反应（ABR）检测听阈值、还原型尼克酰胺腺嘌呤二核甘酸—黄递酶（NADPH－d）酶组化法检测一氧化氮合酶NOS1活性。结果联合用药组可以显著降低应用庆大霉素而增高的ABR阈值（P<0.01)及NOS活性(P<0.01),且NOS活性增高与ABR阈值增高存在正相关关系.结论川芎嗪通过减低庆大霉素耳中毒蜗NOS活性,ABR阈值拮抗其耳毒性     

Nitric oxide: therapeutic opportunities

Fifteen years after the discovery of nitric oxide as a biological mediator how close are new therapies? This article describes the roles of nitric oxide, illustrates how its discovery is altering the way in which certain established drugs are being used and reviews new therapeutic developments.     

雾化吸入氯胺酮对哮喘大鼠肺组织一氧化氮及一氧化氮合酶的影响

目的通过建立大鼠支气管哮喘模型,观察不同浓度氯胺酮对哮喘大鼠肺组织iNOS活性及NO含量的影响。方法SD大鼠随机分成对照组(N组)、哮喘模型组(A组)、不同浓度氯胺酮预处理组(分别为K1组、K2组)和地塞米松组(D组),每组8只。A组大鼠用卵白蛋白辅以百日咳杆菌菌苗和氢氧化铝为佐剂注射致敏,2周后雾化吸入卵蛋白激发哮喘;氯胺酮处理组大鼠用同样方法致敏,但在激发前分别给予雾化吸入氯胺酮25 g/L(K1组)和50 g/L(K2组);D组在激发前给予雾化吸入0.01%地塞米松;N组用生理盐水替代卵蛋白进行注射和吸入。每组分别测定其肺组织NO2-/NO3-水平、肺组织诱导型NOS(iNOS)和原生型NOS(cNOS)活性水平,并用免疫组织化学法观察iNOS在大鼠哮喘模型肺组织中的分布。结果A组肺组织中NO2-/NO3-和iNOS水平升高,iNOS和肺组织NO2-/NO3-水平呈高度正相关;K1、K2组肺组织中NO2-/NO3-和iNOS水平低于A组(P<0.05);D组肺组织中NO2-/NO3-和iNOS水平亦低于A组(P<0.05)。结论25 g/L或50 g/L的氯胺酮雾化吸入可抑制哮喘大鼠肺组织iNOS活性,降低NO含量,减轻大鼠肺部炎症。     

Nitric Oxide-based Possibilities for Pharmacotherapy

The goal of nitric oxide (NO) based pharmacotherapy is to reach proper homeostasis of NO metabolism in the target tissue where endogenous production of NO is either too weak or excessively increased. In addition to the classic NO-based therapy of cardiovascular conditions with nitrates, a variety of new therapeutic possibilities have emerged including sexual disorders, gastrointestinal system, immunology, tumour growth regulation and respiratory disorders. NO levels of target tissues can be affected directly by NO donors, or indirectly by increasing the level of L-arginine, a substrate of nitric oxide synthase (NOS). While increased production of NO by induceable NOS (iNOS) by, for example, cytokines does not at present seem therapeutically meaningful, increased NO production by constitutive NOS (cNOS) may be involved in the beneficial effects of ACE inhibitors or oestrogens. NO production may be pharmacologically decreased by inhibition of expression of iNOS by glucocorticoids while both cNOS and iNOS derived NO production is inhibited by administration of false substrates, for example L-NAME. Additionally, the respiratory system and related vessels can be reached directly and more selectively by inhalation of pure NO gas. Possible problems in administering NO and perhaps some NO-donors include the toxic nature of the compound itself whereby vital enzyme systems may be inhibited and tissue damaging radicals formed. Future prospects of NO-based pharmocotherapy may feature selective ligands to different NOS isoforms and tissue selective donors that release NO in a controlled fashion.     

Nitric oxide in the human uterine cervix: Endogenous ripening factor

The human uterine cervix can produce nitric oxide (NO), a free radical with an ultra‐short half‐life. The release of NO changes during pregnancy and is increased in early nonviable pregnancies compared to normal uncomplicated pregnancies. This review concentrates on the role of NO release in cervical ripening in pregnant women. Also some suggestions on future aspects are discussed.     

Low‐intensity ultrasound increases endothelial cell nitric oxide synthase activity and nitric oxide synthesis

Summary. Low‐intensity ultrasound (US) increases tissue perfusion in ischemic muscle through a nitric oxide (NO)‐dependent mechanism. We have developed a model to expose endothelial cells to well‐characterized acoustic fields in vitro and investigate the physical and biological mechanisms involved. Human umbilical vein endothelial cells (HUVEC) or bovine aortic endothelial cells (BAEC) were grown in tissue culture plates suspended in a temperature‐controlled water bath and exposed to US. Exposure to 27 kHz continuous wave US at 0.25 W cm^?2 for 10 min increased HUVEC media NO by 102 ± 19% (P < 0.05) and BAEC by 117 ± 23% (P < 0.01). Endothelial cell NO synthase activity increased by 27 ± 24% in HUVEC and by 32 ± 16% in BAEC (P < 0.05 for each). The cell response was rapid with a significant increase in NO synthesis by 10 s and a maximum increase after exposure for 1 min. By 30 min post‐exposure NO synthesis declined to baseline, indicating that the response was transient. Unexpectedly, pulsing at a 10% duty cycle resulted in a 46% increase in NO synthesis over the response seen with continuous wave US, resulting in an increase of 147 ± 18%. Cells responded to very low intensity US, with a significant increase at 0.075 W cm^?2 (P < 0.01) and a maximum response at 0.125 W cm^?2. US caused minor reversible changes in cell morphology but did not alter proliferative capacity, indicating absence of injury. We conclude that exposure of endothelial cells to low‐intensity, low‐frequency US increases NO synthase activity and NO production, which could be used to induce vasodilatation experimentally or therapeutically.     

Nitric oxide and the control of renin secretion

Summary— Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, renal, immune and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, pituitary and other endocrine glands, and evidence is accumulating that it contributes to the regulation of the secretion of renin by the kidneys. The enzyme nitric oxide synthetase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa , a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney and is responsive to changes in nitric oxide levels. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro , suggesting a stimulatory role for the L-arginine-nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa and beta adrenoceptor mechanisms that regulate renin secretion. Future research should clarify the mechanisms by which nitric oxide regulates the secretion of renin and establish the physiological significance of this regulation.     

大鼠创伤性脑水肿一氧化氮及其合成酶的变化

目的：探讨脑损伤后一氧化氮（ＮＯ）及一氧化氮合酶（ＮＯＳ）与脑水肿的关系。方法：建立大鼠创伤性脑水肿模型,按不同时间点处死动物,测定其脑含水量及静脉血ＮＯ 和脑组织中ＮＯＳ。结果：脑创伤后脑含水量随静脉血ＮＯ的增加而增加,组织ＮＯＳ则随ＮＯ 的增加而下降。结论：创伤性脑水肿与血ＮＯ 有密切相关性,组织中ＮＯＳ则是该过程的可能催化剂     

一氧化氮合酶抑制剂对严重烧伤大鼠的作用研究

目的 :研究一氧化氮合酶 (NOS)抑制剂对严重烧伤大鼠体内一氧化氮 (NO)含量及 NOS表达的影响及其与预后的关系。方法 :复制大鼠重症烧伤模型 ,检测应用非选择性 NOS抑制剂 N 硝基 L 精氨酸甲酯(L NAME)和选择性诱生型 NOS(i NOS)抑制剂氨基胍 (AG)后大鼠血液中 NO代谢产物 (NO- 2 /NO- 3 )以及肺和十二指肠组织中神经型 NOS(n NOS) m RNA的表达水平 ,同时统计各组大鼠的存活率。结果 :烧伤后大鼠血液中 NO- 2 /NO- 3 含量明显增高 ,L NAME和 AG都能抑制 NO2 /NO- 3 的升高 ,L NAME作用更为明显 ;烧伤后 n NOS的 m RNA表达在肺和十二指肠中均有不同程度升高 ,AG和 L NAME使 n NOS表达增加 ,AG作用更为明显 ;L NAME组动物存活时间较对照组显著缩短 ,AG组动物存活时间明显延长。结论 :结构型NOS(c NOS)与 i NOS在烧伤休克病理生理过程中的作用明显不同 ,i NOS活性过度增高与烧伤休克发病关系密切     

Endothelial nitric oxide synthase (Glu298Asp) polymorphism is an independent risk factor for migraine with aura

OBJECTIVE: The aim of the present study was to evaluate whether the functional endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism, which has been demonstrated to decrease the endothelial NOS activity, might be a risk factor for migraine. BACKGROUND: It has widely demonstrated that nitric oxide (NO) is involved in migraine pathogenesis. Several genetic risk factors have been associated with migraine, but no study has unraveled a possible relationship between migraine and eNOS Glu298Asp. Methods.-One hundred fifty-six migraine patients and 125 healthy nonheadache volunteers entered the study. Demographic and clinical characteristics were carefully recorded, and a neurological workup was performed. RESULTS: eNOS AspAsp homozygous patients had a 3-fold time risk for migraine with aura (MA) when compared to migraine without aura (MO) patients (OR-3.02, 95% CI-1.21 to 7.51), and more than 2-fold time increased risk when compared to control subjects (OR-2.21, 95% CI-1.00 to 5.04). In migraine patients, no difference in age at onset, mean attack's intensity, family history for any of the studied comorbidities, or the presence of comorbidities was found in eNOS AspAsp homozygous compared to eNOS GluGlu or eNOS GluAs carriers. CONCLUSIONS: Homozygous Asp298, a common variant of the eNOS gene, is an independent risk factor for MA in this study population.     

N-acetyl-L-cysteine exerts direct anti-aggregating effect on human platelets

BACKGROUND: N-acetyl-L-cysteine, a thiol compound, has been shown to potentiate the inhibition of platelet aggregation exerted by organic nitrates and to increase the anti-aggregating effect of L-arginine, which promotes endogenous synthesis of nitric oxide (NO) acting as substrate of platelet constitutive nitric oxide synthase (NOS). It is not known whether this thiol can exert direct effects on platelet aggregability. MATERIALS AND METHODS: 14 healthy male volunteers provided platelet samples to investigate whether N-acetyl-L-cysteine directly influences platelet function and intraplatelet levels of 3',5' cyclic guanosine monophosphate (cGMP), which represents the second messenger involved in NO-induced antiaggregation. Some experiments were repeated in the presence of NOS inhibitor NG-monomethyl-L-arginine (L-NMMA), of nitric oxide-sensitive guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), of the selective cGMP phosphodiesterase inhibitor zaprinast and of calcium ionophores (A23187, ionomycin). RESULTS: N-acetyl-L-cysteine at 3000-6000 micromol L-1 decreases the responses of human platelets both in platelet-rich plasma (aggregation induced by adenosine 5-diphosphate) and in whole blood (aggregation induced by collagen). The anti-aggregating effect was prevented by preincubation with L-NMMA and guanylyl cyclase inhibitor ODQ. In resting platelets, N-acetyl-L-cysteine increased the levels of cGMP starting from a concentration of 3000 micromol L-1. Permeabilized platelets exhibited an increased sensitivity to the anti-aggregating effect of N-acetyl-L-cysteine. Also, cGMP phosphodiesterase inhibition or the increase in calcium availability, enhanced N-acetyl-L-cysteine effects on platelets. CONCLUSION: N-acetyl-L-cysteine exerts direct anti-aggregating effects through an increased bioavailability of platelet nitric oxide.