Gender differences in genotypic distribution of endothelin-1 gene and endothelin receptor A gene in pulmonary hypertension associated with rheumatic mitral valve disease

IntroductionThe female gender is a risk factor for idiopathic pulmonary arterial hypertension. However, it is unknown whether females with rheumatic mitral valve disease are more predisposed to develop pulmonary hypertension compared to males.AimWe aimed to investigate whether there was a difference in genotypic distribution of endothelin-1 (ET-1) and endothelin receptor A (ET_A) genes between female and male patients of pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD).MethodsWe compared prevalence of ET-1 gene (Lys198Asn) and ET_A gene (His323His) polymorphisms according to gender in 123 PH-MVD subjects and 123 healthy controls.ResultsThe presence of mutant Asn/Asn and either mutant Asn/Asn or heterozygous Lys/Asn genotypes of Lys198Asn polymorphism when compared to Lys/Lys in females showed significant association with higher risk (odds ratio [OR] 4.5; p =0.007 and OR 2.39; p =0.02, respectively). The presence of heterozygous C/T and either mutant T/T or heterozygous C/T genotypes of His323His polymorphism when compared to wild C/C genotype in females showed a significant association with higher risk (OR 1.96; p =0.047 and OR 2.26; p =0.01, respectively). No significant difference was seen in genotypic frequencies in males between PH-MVD subjects and controls. Logistic regression analysis showed that mutant genotype Asn/Asn (p =0.007) and heterozygous genotype Lys/Asn of Lys198Asn polymorphism (p =0.018) were independent predictors of development of PH in females.ConclusionsET-1 and ET_A gene polymorphisms were more prevalent in females than males in PH-MVD signifying that females with rheumatic heart disease may be more susceptible to develop PH.     

Endothelin-1 induces chondrocyte senescence and cartilage damage via endothelin receptor type B in a post-traumatic osteoarthritis mouse model

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Altered release of endothelin-1,2 and thromboxane B2 from trophoblastic cells in pre-eclampsia

The aim of the study was to investigate whether pre-eclampsia is associated with an altered release of vasoactive substances from trophoblastic cells in vitro . Trophoblastic cells from 15 uncomplicated control pregnancies and 18 pre-eclamptic pregnancies at preterm (weeks 31–36; n  = 12) and term (weeks 37–40; n  = 21) were cultured for 5 days. The concentrations of angiotensin II (AII), endothelin-1,2 (ET-1,2), thromboxane B₂ (TXB₂), 6-keto-prostaglandin F_1α (6-keto-PGF1_α) and leukotriene B₄ (LTB₄) were measured daily in culture media for 5 days by radioimmunoassay. In pre-eclampsia, concentrations of ET-1,2 were decreased ( P < 0.01) at both preterm and term, TXB₂ concentrations were increased P < 0.05) only at preterm and the TXB₂–6-keto-PGF_1α ratio was increased at both preterm and term ( P < 0.01) as compared with the controls. Concentrations of AII, 6-keto-PGF_1α and LTB₄ were similar to the controls. The data suggest that pre-eclampsia is associated with a decreased release of ET-1 and an increased release of TXB₂ from trophoblastic cells in vitro     

尿毒症患者血浆同型半胱氨酸及内皮细胞功能变化的意义

目的探讨血浆同型半胱氨酸（Hcy）水平变化对尿毒症患者的意义及尿毒症患者Hcy与内皮细胞功能的关系。方法采用酶联免疫吸附试验（ELISA）测定59例尿毒症患者Hcy、血浆血管性血友病因子（vwF）、内皮素-1（ET-1）、血栓调节蛋白（TM），应用化学比色法检测一氧化氮（NO），并比较各指标在尿毒症组与对照组间的差异；同时评价尿毒症患者肾小球滤过率（GFR）、肌酐（Cr）与Hcy之间的相关性；评价GFR、Cr、Hcy与反映内皮细胞功能指标之间的相关性结果尿毒症患者组GFR为（5．19±1．88）mL／min，Cr为（1146．81±304．57）μmol／L。血浆Hcy、NO、ET-1、WF、TM与对照组比较差异有统计学意义（P〈0．05、P〈0．01）。尿毒症患者NO／ET-1比值明最低于对照组。在尿毒症组中，Hcy与GFR呈负相关（r=-0．369，P=0．04），和Cr呈正相关（r=0．274，P=0．039）；GFR与TM呈负相关（r=-0．278，P=0．035）。结论Hcy与尿毒症有密切的关系，高Hcy血症是尿毒症合并心脑血管疾病的独立危险因子，TM是尿毒症患者反映内皮细胞功能损伤最佳的指标，并与肾脏损伤的严重程度相关。     

间歇低氧对大鼠内皮素及其受体基因表达的影响

目的观察慢性间歇低氧诱发大鼠高血压发病过程中内皮素(ET)及其受体的动态变化,探讨慢性间歇低氧诱发高血压的发病机制。方法将Wistar大鼠(n=72)随机均分为间歇低氧组(IH组)、实验对照组(SC组)和空白对照组(UC组)。IH组大鼠循环给予氮气和压缩空气(每一循环60s,使舱内最低氧浓度达4%~6%,然后恢复至21%,8h/d),SC组大鼠循环给予压缩空气,UC组大鼠不给予任何处理。观察第7、21、42天时各组大鼠的血压、血浆ET-1水平及不同组织ET-1和内皮素A型受体(ETAR)mRNA的表达。结果第42天时IH组大鼠平均动脉压(MAP)较实验前升高约8mmHg(P<0·01),而两对照组大鼠MAP无显著变化。IH组大鼠血浆ET-1水平随间歇低氧时间的延长逐渐升高,从第7天[(157±35)ng/L]开始显著高于SC组[(123±29)ng/L]和UC组[(119±28)ng/L]水平(P<0·05),并且与MAP呈正相关(r=0·605,P=0·002);其心脏和肾皮质ET-1mRNA的表达随间歇低氧时间的延长也逐渐增加,从第21天开始显著高于两对照组水平(P<0·05);其主动脉、心脏和肾皮质ETARmRNA的表达与两对照组比较,差异无显著性(P>0·05)。SC组与UC组比较,各项观察指标差异均无显著性(P>0·05)。结论慢性间歇低氧可导致ET-1表达增加,使血循环ET-1水平升高,而对ETAR的表达没有影响,提示ET-1的过度表达可能是慢性间歇低氧诱发高血压的重要原因之一。     

经皮腔内冠状动脉成形术后内皮素心脏释放动力学的研究

目的　对经皮腔内冠状动脉成形术 (PTCA)后内皮素 (ET)释放的动力学进行估价 ,探讨冠状动脉内皮是否是ET的释放部位。方法　 12例冠脉造影前后、2 0例陈旧性心肌梗死行择期PTCA术前及术后 5min、6h的股静脉血、冠状动脉口血及冠状窦处血 ,用放射免疫法检测ET浓度。结果　冠脉造影前后血浆ET浓度无明显变化 (P >0 0 5 )。PTCA术后 5minET浓度升高 ,与术前相比具有极显著性差异 (P <0 0 1) ,且持续升高达 6h ,与术前相比具有极显著性差异 (P <0 0 1)。PTCA后冠状动脉口、冠状窦及股静脉处ET浓度均明显升高 ,但冠状窦处最高 ,其与冠状动脉口及股静脉相比均具有显著性差异 ,且冠状动脉口与股静脉处ET浓度相比也具有显著性差异。结论　PTCA可使血浆ET进一步升高 ,冠状动脉内皮可能是ET的释放源     

内皮素和一氧化氮合成酶在家兔动脉粥样硬化斑块中的表达

用免疫组织化学和原位杂交等方法观察了内皮素和一氧化氮合成酶在家兔动脉粥样硬化斑块中的合成和表达，结果是，在动脉粥样硬化斑块内增生的平滑肌细胞和巨噬细胞中，内皮素合成较正常者增多，而一氧化氮合成酶的合成却明显减少，内皮素mRNA转录显著增加，而一氧化氮合成酶mRNA转录明显减少或消失，提示在动脉血管平滑肌细胞中，二者的平衡失调可能参与了动脉弱样硬化的发生和发展过程。     

Resveratrol inhibits the intracellular calcium increase and angiotensin/endothelin system activation induced by soluble uric acid in mesangial cells

Resveratrol (Resv) is natural polyphenol found in grapes. This study evaluated the protective effect of Resv against the effects of uric acid (UA) in immortalized human mesangial cells (ihMCs). ihMCs were preincubated with Resv (12.5 µM) for 1 h and treated with UA (10 mg/dL) for 6 or 12 h. The intracellular calcium concentration [Ca²⁺]i was quantified by fluorescence using flow cytometry. Angiotensinogen (AGT) and pre-pro endothelin-1 (ppET-1) mRNA were assayed by quantitative real-time RT-PCR. Angiotensin II (AII) and endothelin-1 (ET-1) were assayed by ELISA. UA significantly increased [Ca²⁺]i. Pre-incubation with Resv significantly reduced the change in [Ca²⁺]i induced by UA. Incubation with UA for 6 or 12 h also increased AGT mRNA expression and AII protein synthesis. Resv blunted these increases in AGT mRNA expression and AII protein. Incubation with UA in the ihMCs increased ppET-1 expression and ET-1 protein synthesis at 6 and 12 h. When ihMCs were pre-incubated with Resv, UA had a significantly diminished effect on ppET-1 mRNA expression and ET-1 protein synthesis at 6 and 12 h, respectively. Our results suggested that UA triggers reactions including AII and ET-1 production in mesangial cells. The renin-angiotensin system may contribute to the pathogenesis of renal function and chronic kidney disease. Resv can minimize the impact of UA on AII, ET-1 and the increase of [Ca²⁺]i in mesangial cells, suggesting that, at least in part, Resv can prevent the effects of soluble UA in mesangial cells.     

头皮发际区微针疗法对血管性痴呆患者认知功能及内皮素的影响

目的:探讨头皮发际区微针疗法治疗血管性痴呆(VD)的疗效。方法:60例VD患者随机分为两组。其中观测组用头皮发际区微针疗法,对照组用口服药物疗法。方法:采用放射免疫法捡测血浆内皮素(ET)的浓度,采用MMSE和ADL量表评定患者的认知功能、社会活动功能及日常生活能力。结果:两组疗效比较,观测组的总有效率为60.00%,对照组的总有效率为53.33%,二者差异有统计学意义(P0.05);治疗后两组MMSE、ADL量表评分与治疗前自身比较均有显著改善(P0.01);治疗后,观测组的MMSE、ADL量表评分与对照组相比较改善更为明显(P0.05);两组血浆ET水平治疗后较治疗前自身比较均有显著下降(P0.01);治疗后,观测组血浆ET水平与对照组比较,下降更为明显(P0.05)。结论:头皮发际区微针疗法对于VD患者具有确切疗效,其治疗机理与降低血浆ET含量相关。     

化痰祛浊通络方对自发性高血压大鼠血压一氧化氮、内皮素1及血管紧张素Ⅱ的影响

目的：观察化痰祛浊通络方对自发性高血压大鼠（SHR）血压及一氧化氮（NO）、内皮素1（ET－1）及血管紧张素Ⅱ（AngⅡ）的影响,探讨其降压作用机制。方法将15月龄SHR随机分为空白对照组、化痰祛浊通络方组和吲达帕胺组,每组各9只。空白对照组予0．9％氯化钠注射液（10 mL／kg）、化痰祛浊通络方组予化痰祛浊通络方水煎液（生药10 mL／kg）、吲达帕胺组予吲达帕胺溶液（10 mg／kg）,均每日1次灌服,连续6周。所有大鼠每周测量尾动脉压,给药6周腹主动脉抽血测定血清NO、ET－1及AngⅡ含量。结果给药6周后,化痰祛浊通络方组和吲达帕胺组给药后均可降低SHR收缩压（ SP）和舒张压（ DP）,与空白对照组及本组给药前比较差异均有统计学意义（P＜0．05）;化痰祛浊通络方组及吲达帕胺组ET－1和AngⅡ含量均较本组给药前及空白对照组明显降低,NO含量明显升高,差异均有统计学意义（P＜0．05）。结论化痰祛浊通络方能明显降低SHR血压,其机制可能是通过下调ET、Ang Ⅱ含量及上调NO含量来发挥降压作用。