消瘀片对粥样硬化兔血管壁组织中ET、NO及细胞凋亡的影响

目的 :探讨消瘀片减少粥样硬化血管壁中平滑肌细胞数的作用机理。方法 :雄性新西兰兔高脂饮食加腹主动脉内膜剥脱术制成腹主动脉粥样硬化模型 ,通过放免法、比色法、原位末端标记及图像分析技术分别测定连续给予消瘀片 0 .1 6～ 0 .32g/(kg·d)治疗 1 6周后血管壁组织中ET、NO及细胞凋亡的变化。结果 :服用消瘀片后的兔粥样硬化血管壁组织中ET含量降低 ,NO含量增加 ,凋亡细胞阳性反应颗粒所占的面积和积分光密度值减少。结论 :消瘀片通过降低血管壁中的ET而抑制平滑肌细胞的增生 ,通过增加血管壁中的NO诱导细胞凋亡及加强对凋亡细胞的清除     

力平脂对兔粥样硬化血管壁组织内内皮素-1和一氧化氮合酶mRNA表达的影响(英文)

目的:探讨力平脂消退动脉粥样硬化的作用机制民。方法:给兔喂饲高脂饲料8周,加腹主动脉内皮损伤造成腹主动脉粥样硬化模型,然后用力平脂15mg·kg~(-1)·d~(-1)治疗16周。粥样硬化血管壁组织中内皮素(ET)-1和一氧化氮合酶(NOS)mRNA的表达分别采用原位杂交和逆转录多聚酶链反应(RT-PCR)测定。结果:力平脂治疗16周后,ET-1 mRNA表达明显减少,其阳性杂交颗粒的积分光密度(IOD)和面积分别由粥样硬化组的(65188±10113)和(3028±352)μm~2下降至(49113±16868)和(2448±621)μm~2。力平脂也可降低诱导型NOS mRNA的表达,使IOD和面积分别下降25.5％和53.3％,但通过RT-PCR测得的内皮型NOS mRNA表达增加。结论:恢复ET-1 mRNA/NOS mRNA的平衡可能是力平脂消退动脉粥样硬化的机制之一。     

一氧化氮在内皮素-1诱导神经元凋亡中的作用

目的:证实内皮素-1(endothelin-1,ET-1)(2×10-7M)诱导培养大鼠大脑皮层神经元凋亡及刺激神经元释放内源性一氧化氮(NO)的作用;了解NO在该浓度ET-1诱导神经元凋亡中的作用。方法:神经元培养取自乳鼠大脑皮质细胞,培养5d后分3组实验:对照组(空白)、ET-1组(2×10-7M)、ET-1 L-NAME(左旋精氨酸甲酯,NO合成抑制剂,100mM)组,继续培养24h。收集细胞,用流式细胞仪定量检测凋亡率;收集培养上清液,用硝酸还原酶法检测NO浓度。结果:ET-1(20nM)处理后24h,培养大鼠大脑皮层神经元的凋亡率显著高于对照组(P<0.001)。L-NAME明显阻断了ET-1诱导神经元凋亡的作用,与ET-1组比较,凋亡率降幅为40%(P<0.05)。经ET-1处理后24h,神经元培养液中NO浓度均较对照组显著高(P<0.001)。而L-NAME完全抑制了ET-1引起的培养液中NO的升高。结论:ET-1(20nM)有诱导培养大鼠大脑神经元凋亡的作用;该作用与ET-1刺激培养大鼠大脑神经元合成和释放内源性谷氨酸和NO增加有关;NO合酶抑制剂能显著减轻ET-1诱导的神经元凋亡率。提示ET-1诱导培养大鼠大脑神经元凋亡通过NO途径。     

高尿酸血症对血清一氧化氮及内皮素-1水平的影响

目的:观察高尿酸血症对血清一氧化氮(NO)及内皮素-1(ET-1)水平的影响.方法:检测92例观察对象血尿酸水平,分为高血尿酸组( HUA)45例与正常血尿酸组(NUA)47例,分别检测2组每一个体的血清NO及ET -1水平进行比较分析.结果:HUA组NO水平低于NUA组(P＜0.01);HUA组ET -1水平高于NU...     

纳洛酮对心肌缺血—再灌注损伤血浆内皮素-1和一氧化氮的影响

目的 探讨纳洛酮在心肌缺血-再灌损伤时对血浆内皮素-1(ET-1)和一氧化氮(NO)的影响。方法 复制心肌缺血-再灌注模型,观察血浆内皮素-1和一氧化氮的动态变化及纳洛酮的影响。制作心肌缺血模型和缺血-再灌注损伤模型,并抽取不同时间点的静脉血。采用放射免疫法测定ET-1的含量,硝酸还原酶法测定NO的含量。结果 心肌缺血后ET-1水平呈上升趋势,4 h达高峰;而NO水平明显下降。缺血再灌注后0.5～1h ET-1含量高于缺血前(P<0.O5);纳洛酮保护组ET-1含量均低于缺血前(P0.05)。而NO水平在缺血再灌注后均下降;保护组NO含量均高于缺血前(P<0.05);治疗组NO含量在缺血后0.5 h低于缺血前,其余各时间点与缺血前比较差异均无显著性(P>0.05)。结论 纳洛酮可有效降低心肌缺血及缺血再灌注损伤时血浆ET-1和提高NO水平;从而减轻ET-1对血管和心肌组织的损伤作用。     

妊高征病人血浆内皮素-1及一氧化氮水平的动态分析

本文通过观察妊高征孕妇血浆ET 1及NO的变化 ,旨在分析、探讨妊高征发病机制。现报告如下。1　资料与方法1 1　调查对象　系 2 0 0 0年至 2 0 0 2年 2月本院产科住院孕妇 ,共计 5 6例 ,其中妊高征孕妇 32例 ,年龄 2 2～ 34岁 ,平均2 6岁。其诊断标准按高等院校统编教材《妇产科学》第 5版 ,分为重度妊高征 14例 ,中度妊高征 10例及轻度妊高征 8例。孕周为 37～ 4 1周。取同期住院的 2 4例正常晚孕妇女(正常妊娠组 )和 18例正常非孕妇女 (正常未孕组 )作对照。正常妊娠组均为单胎初产妇 ,年龄 2 1～ 33岁 ,既往无高血压、心脏病、肾病史。1…     

支气管哮喘患儿血内皮素-1和一氧化氮水平测定及临床意义

目的　探讨内皮素 1(Endothelia 1,ET 1)和—氧化氮 (nitrcoxide ,NO )在儿童哮喘发病机制中的作用。方法　对 40例支气管哮喘患儿和 40例正常儿童进行了血浆ET 1及血清NO水平检测。结果　哮喘急性期患儿血ET 1和NO明显高于缓解期 (P <0 0 1) ,缓解期ET 1和NO虽有所下降 ,但仍高于对照组(P <0 0 5)。结论　ET 1和NO水平与哮喘病情严重程度成正相关 ,是反映哮喘严重程度的良好指标     

大鼠肝内型门脉高压症形成中一氧化氮和内皮素—1的动态变化

目的 观察大鼠肝内型门脉高压症形成中一氧化氮(NO)和内皮素—1(ET—1)水平的动态变化，探讨其在门脉高压症形成高动力循环中的作用。方法 以四氯化碳(CCl4)注射法制备肝内型门脉高压症大鼠模型，分别用硝酸还原酶和放免法检测正常组、CCl4组及对照组(橄榄油注射组)不同时点的门静脉血浆NO2^-／NO3^-、ET-1水平，并同步监测血流动力学指标的动态变化。结果 COl4注射8周大鼠血浆NO2^-／NO3^-水平显著升高而ET-1水平显著低于相应对照组，同时伴有血流动力学的显著变化。结论 门脉高压症大鼠存在高动力循环状态(HCS)。NO和ET-1参与HCS的形成和维持。     

一氧化氮及内皮素1在急性肾功能衰竭中的作用

目的 观察一氧化氮（NO）和内皮素1（ET-1）含量变化在急性肾功能衰竭（ARF）中的作用。方法 实验用肌肉注射甘油和皮下注射HgCl2法复制成大鼠ARF模型,以硝酸还原法、化学显色法分别检测血清及肾组织NO含量及其一氧化氮合成酶NOS、iNOS活性,并用放免检测和免疫组化方法对ARF大鼠肾组织中ET-1进行定量与定位分析。结果 模型组NO含量及其合酶活性均显著增加,ET-1水平在24h明显增高,以后逐渐降低。结论 NO及其合酶、ET-1在ARF的发生、发展过程中均起着重要的作用。     

噻嗪类利尿剂对自发性高血压大鼠内皮型一氧化氮合酶和内皮素-1表达影响的研究

目的研究噻嗪类利尿剂治疗自发性高血压大鼠时对其内皮型一氧化氮合酶和内皮素-1表达的影响,从而探讨其降压的可能分子机制。方法15只自发性高血压大鼠随机分为3组,分别经胃管给予氢氯噻嗪(HCTZ,10 mg.kg-1.d-1)、吲哒帕胺(IND,0.625 mg.kg-1.d-1)和等量去离子水。每周测血压1次,4 wk后处死动物,分别用RT-PCR和W estern B lot法检测组织中内皮素-1和内皮型一氧化氮合酶mRNA和蛋白质的表达。结果氢氯噻嗪和吲哒帕胺用药1 wk后SHR的血压降低,2wk时降压幅度达到显著水平(P<0.05)。同时两种利尿剂均可在蛋白质水平上调内皮型一氧化氮合酶的表达,在mRNA水平下调内皮素-1的表达。结论噻嗪类利尿剂可能通过上调内皮型一氧化氮合酶及下调内皮素-1而起到调节血压与改善血管内皮功能作用。     

依那普利拉通过调控ET-1水平和NO含量抗新生鼠心室成纤维细胞增殖

目的观察血管紧张素Ⅰ转换酶抑制剂(angiotensinⅠconverting enzyme inhibitor,ACEI)依那普利拉(enalaprilat,Ena)对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导的新生大鼠心室成纤维细胞(cardiac fibroblast,CFb)增殖及其对内皮素-1水平和一氧化氮含量的影响,探讨Ena抑制CFb增殖的初步机制。方法以培养的新生Wistar大鼠CFb为研究对象,分为对照组、模型组、给药组3个剂量组,采用胰酶消化、差速贴壁法培养CFb,四氮唑盐(MTT)比色法检测细胞增殖;羟脯氨酸(HYP)法测定胶原蛋白含量;流式细胞仪测定细胞周期;硝酸还原酶法和放射免疫法分别测定不同干预条件下CFb培养液中ET-1水平和NO含量。结果Ena能够明显抑制AngⅡ诱导的CFb增殖,降低HYP含量(P<0.05或P<0.01);提高细胞周期中G0/G1期百分率、降低S期百分率(P<0.05或P<0.01);降低ET-1水平、提高CFbNO含量,并呈剂量和时间依赖性(P<0.05或P<0.01)。结论Ena抗增殖的作用与改善CFbET-1水平和NO含量,即降低ET-1,升高NO含量,拮抗AngⅡ的生物效应有关。     

松龄血脉康对糖尿病患者血浆一氧化氮、前列环素和内皮素-1水平的影响

目的研究松龄血脉康对糖尿病(DM)患者血浆一氧化氮(NO)、前列环素(PGI2)和内皮素-1(ET-1)水平的影响.方法60例2型DM患者随机分为实验组和对照组,2组一般治疗基本相同,实验组加用松龄血脉康,1.5g,tid,连用12wk.测定治疗前后空腹血糖(FBG)、糖化血红蛋白A1c(GHbA1c)及血浆NO、PGI2、ET-1水平.结果治疗前2组各项指标比较差别无显著性(P＞0.05).治疗后实验组血浆NO、PGI2水平较治疗前显著上升(P＜0.01),ET-1显著下降(P＜0.01);FBG、GHbA1c无明显变化(P＞0.05).对照组治疗前后所有指标均无明显变化(P＞0.05).结论松龄血脉康可改善DM患者血管内皮细胞功能,能有效调节DM患者血浆NO、PGI2、ET-1水平,对DM具有一定的辅助治疗价值.     

Myoendothelial coupling in the mesenteric arterial bed; segmental differences and interplay between nitric oxide and endothelin-1

Background and purpose:

We tested the hypothesis that activated arterial smooth muscle (ASM) stimulates endothelial vasomotor influences via gap junctions and that the significance of this myoendothelial coupling increases with decreasing arterial diameter.

Experimental approach:

From WKY rats, first-, second-, third-and fourth-order branches of the superior mesenteric artery (MA1, MA2, MA3 and MA4 respectively) were isolated and mounted in wire-myographs to record vasomotor responses to 0.16–20 µmol·L⁻¹ phenylephrine.

Key results:

Removal of endothelium increased the sensitivity (pEC₅₀) to phenylephrine in all arteries. The nitric oxide (NO) synthase inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME) (100 µmol·L⁻¹) did not modify pEC₅₀ to phenylephrine in all denuded arteries, and increased it in intact MA1, MA2 and MA3 to the same extent as denudation. However, in intact MA4, the effect of L-NAME was significantly larger (ΔpEC₅₀ 0.57 ± 0.02) than the effect of endothelium removal (ΔpEC₅₀ 0.20 ± 0.06). This endothelium-dependent effect of L-NAME in MA4 was inhibited by (i) steroidal and peptidergic uncouplers of gap junctions; (ii) a low concentration of the NO donor sodium nitroprusside; and (iii) by the endothelin-receptor antagonist bosentan. It was also observed during contractions induced by (i) calcium channel activation (BayK 8644, 0.001–1 µmol·L⁻¹); (ii) depolarization (10–40 mmol·L⁻¹ K⁺); and (iii) sympathetic nerve stimulation (0.25–32 Hz).

Conclusions and implications:

These pharmacological observations indicated feedback control by endothelium of ASM reactivity involving gap junctions and a balance between endothelium-derived NO and endothelin-1. This myoendothelial coupling was most prominent in distal resistance arteries.     

Endothelin-1 induces vasodilation in human skin by nociceptor fibres and release of nitric oxide

Aims Endothelin is a peptide produced by endothelial cells with many biological properties. In the human skin microcirculation endothelin induces neurogenic vasodilation associated with burning pruritus. We investigated the mechanisms involved in this response.
Methods The effects of prolonged pretreatment with capsaicin, a specific inhibitor of polimodal nociceptor fibres, and of the nitric oxide synthase inhibitor l-NMMA on endothelin-1-induced vasodilation were studied in 15 human subjects. Furthermore, we investigated the effects of the ET_A -selective antagonist PD147953 on bradykinin-induced vasodilation.
Results After local injection, endothelin-1 caused vasoconstriction at the injection site and a profound vasodilation in the surrounding area (flare reaction, P <0.01). This response was specific and not induced by saline, albumin, acetylcholine or an ET-antagonist. Prolonged capsaicin pretreatment inhibited endothelin-1 induced vasodilation in the area surrounding the injection site, but not the central vasoconstriction at the injection site. Bradykinin also induced a marked vasodilation in the area surrounding the injection site; this was not inhibited by an ET_A -selective antagonist, while the flare reaction was. l-NMMA applied at the site of the flare reaction prevented endothelin-1-induced vasodilation.
Conclusions Endothelin-1 in the human skin microcirculation stimulates polimodal nociceptor fibres leading to the release of nitric oxide. This response may play a pathophysiological role in inflammatory processes in the human skin.     

盐酸埃他卡林对血管内皮细胞分泌功能的影响

目的 :研究新型抗高血压药物盐酸埃他卡林(Ipt)对血管内皮细胞分泌功能的影响。方法 :采用灌流消化法分离小牛主动脉内皮细胞 (BAEC) ,观察Ipt对BAEC分泌内皮素 1(ET 1)、前列环素 (PGI2 )和一氧化氮 (NO)的影响 ,同时观察Ipt对培养的BAEC胞浆游离Ca2 浓度的影响。结果 :在Ipt浓度为 10 -6mol·L-1及以上时 ,能够剂量依赖性地抑制培养的BAEC合成分泌ET 1,并在Ipt 10 -5mol·L-1及以上时促进NO的合成分泌 ,同时在Ipt浓度为10 -4mol·L-1及以上时 ,显著地增高BAEC胞浆游离Ca2 浓度。结论 :Ipt通过抑制内皮细胞合成分泌ET 1和促进NO的合成分泌 ,从而使ET和NO的平衡状态得到改善 ;尚能增加内皮细胞 [Ca2 ]i,有利于内皮细胞合成NO增加 ,从而增强内皮介导的舒血管效应。     

Effects of hesperidin on cyclic strain-induced endothelin-1 release in human umbilical vein endothelial cells

1. Hesperidin, a member of the flavanone group of flavonoids, can be isolated in large amounts from the rinds of some citrus species and has been reported to have antihypotensive and vasodilator properties. However, the mechanism of action of hesperidin in the prevention and treatment of vascular diseases remains unclear. 2. The vascular endothelium can produce potent contracting factors, such as endothelin (ET)-1, and endothelium-derived relaxing factors, such as nitric oxide (NO). The aims of the present study were to test the hypothesis that hesperidin may alter strain-induced ET-1 secretion and NO production and to identify the putative underlying signalling pathways in human umbilical vein endothelial cells (HUVEC). 3. Hesperidin (10 and 100 micromol/L) inhibited strain-induced ET-1 secretion. Hesperidin also inhibited strain-induced increases in the formation of reactive oxygen species and extracellular signal-regulated kinase (ERK) phosphorylation. 4. Hesperidin treatment of HUVEC enhanced NO production, endothelial NO synthase (eNOS) activity and the phosphorylation of eNOS and Akt. Furthermore, hesperidin modulated strain-induced ET-1 release and suppressed ERK phosphorylation in part via the NO/protein kinase G pathway. 5. In summary, we have demonstrated that hesperidin inhibits strain-induced ET-1 secretion and enhances NO production in HUVEC.