肾胺酶基因多态性与纵向血压变化和高血压发生的关联性

目的 肾胺酶是由肾脏分泌的一种黄素蛋白胺氧化酶,通过降解循环中的儿茶酚胺发挥血压调节作用.本研究旨在分析人体肾胺酶基因多态性与远期血压变化及高血压发病的关系.方法 2004年在陕西宝鸡农村选取124个家系的515名受试者建立"盐敏感高血压研究队列",并分别于2009、2012和2018年对该队列进行长达14年的随访.采...     

慢性盐负荷及补钾对健康成人血压变异性的影响

目的:探讨慢性盐负荷及补钾对健康成人血压和血压变异性的影响。方法:选取100例年龄在28～60岁的血压正常者参与为期3周的慢性盐负荷及补钾试验,包括基线调查3 d,低盐饮食、高盐饮食和高盐补钾饮食各7 d的研究。在基线调查和各干预阶段的第5,6,7天采用英国产随机零点血压计连续测量3 d血压。测量血压前受试者静坐休息5 min,测量3次,求平均值,并计算3 d血压测量值的标准差和变异系数,作为长时血压变异性指标。结果:受试者血压在低盐期较基线期显著下降［SBP:(112±11)mmHg vs.(117±14)mmHg;DBP:(74±8)mmHg vs.(76±10)mmHg,P<0.01］;高盐期较低盐期明显升高［SBP:(119±14)mmHg vs.(112±11)mmHg;DBP:(77±9)mmHg vs.(74±8)mmHg,P<0.01］;补钾期较高盐期显著降低［SBP:(114±12)mmHg vs.(119±14)mmHg;DBP:(75±8)mmHg vs.(77±9)mmHg,P<0.01］。限盐后收缩压标准差、舒张压标准差均降低［SDSBP:(3.9±1.5)mmHg vs.(4.3±1.0)mmHg;SDDBP:(3.2±1.4)mmHg vs.(3.6±1.6)mmHg,P<0.01］;高盐期较低盐期升高［SDSBP:(4.4±1.6) vs.(3.9±1.5)mmHg;SDDBP:(3.7±1.2) vs.(3.2±1.4)mmHg,P<0.01］。结论:钠、钾摄入量与血压变化密切相关,其中低盐饮食后血压下降,高盐饮食后血压升高,而在高盐负荷基础上给予大剂量补钾使血压下降。高盐饮食可增大血压变异性,限盐可降低血压变异性。     

慢性盐负荷对血压正常盐敏感性个体胰岛素抗性的影响

目的观察慢性盐负荷对血压正常盐敏感者个体胰岛素抗性的影响。方法对２３例血压正常的健康志愿者，通过３天的平衡饮食期（ＮａＣｌ１４ｇ／ｄ），７天的高盐饮食期（ＮａＣｌ２３ｇ／ｄ）及７天的低盐饮食期（ＮａＣｌ３ｇ／ｄ）在确定盐敏感性的同时，进行口服葡萄糖耐量试验及胰岛素释放试验。结果盐敏感者慢性高盐负荷使空腹血胰岛素水平及胰岛素释放量明显增加，与盐不敏感者差异显著，空腹血胰岛素为１２．２±５．７对７．４±１．７μＵ／ｍｌ，胰岛素曲线下面积分别为７４．６±２１．９对３９．０±１２．４μＵ·ｈ－１·Ｌ－１，Ｐ均＜０．０５；敏感者高盐负荷后与平衡饮食期相比，葡萄糖负荷试验后的１ｈ及曲线下面积亦有升高倾向。结论高盐摄入在升高盐敏感者血压的同时，胰岛素抗性也增加     

地龙降压胶囊对自发性高血压大鼠肾胺酶表达的影响

目的:观察地龙降压胶囊对自发性高血压大鼠(SHR)肾胺酶表达的影响,以探讨地龙降压胶囊治疗原发性高血压的作用机制。方法:取24只8周龄雄性SHR,根据收缩压随机分为模型组(等容量蒸馏水灌胃)及地龙降压胶囊高、低剂量组(分别以地龙降压胶囊240mg/kg、120mg/kg灌胃),每组8只。另取8只WKY雄性大鼠作为正常对照组(等容量蒸馏水灌胃)。分别于连续给药前、给药后第2周、4周、6周、8周测定尾动脉收缩压。末次给药后,采用ELISA法检测大鼠血浆儿茶酚胺和血清肾胺酶含量。采用免疫组织化学法检测大鼠肾脏肾胺酶的表达。结果:地龙降压胶囊有效降低了SHR收缩压、血浆儿茶酚胺水平(P<0.05);升高了SHR肾胺酶水平(P<0.05)。结论:地龙降压胶囊能有效降低血压,其作用机制可能是通过调节肾胺酶表达水平,从而影响血浆儿茶酚胺水平实现的。     

急性静脉盐水负荷与慢性盐负荷试验在盐敏感性检测的对照研究

目的探讨急性静脉盐水负荷试验盐敏感性个体的检出与慢性盐负荷试验的一致性。方法２３例血压正常健康志愿者先后进行慢性盐负荷试验和急性静脉盐水负荷试验。前者高盐与低盐饮食期各７天，每日摄盐量分别为２３ｇ和３ｇ。后者于４ｈ内静脉输注０．９％盐水２０００ｍｌ，２ｈ后服速尿４０ｍｇ，观察血压直至服速尿２ｈ末。结果慢性与急性盐负荷试验的盐敏感性个体检出符合率为１００％；二者对盐负荷的血压增幅反应相关性良好（ｒ＝０．８５，Ｐ＜０．０１）。慢性盐负荷试验高盐期的血压明显升高发生持续到盐负荷中的第６天，而低盐期的减幅反应出现在第３天。结论急性静脉盐水负荷试验盐敏感性的检出与慢性盐负荷试验完全一致，前者可以替代后者用于人群盐敏感性的检测。     

肾胺酶在心血管疾病发生发展中的作用机制研究进展

肾胺酶（renalase）是一种依赖黄素腺嘌呤二核苷酸的胺氧化酶,主要由肾小管近端上皮细胞合成和分泌,在心脏、肝脏、胰腺、骨骼肌和生殖系统中广泛表达。renalase能够降解血液循环中的儿茶酚胺,可作为一种细胞因子在高血压、动脉粥样硬化、冠状动脉粥样硬化性心脏病、心力衰竭及心房颤动等心血管疾病的发生发展中发挥一定的心脏保护作用。鉴于心血管疾病与肾脏疾病在内分泌调节机制中的联系,renalase是十分有潜力的心血管疾病药物靶点,其临床应用值得进一步关注。     

盐和左旋精氨酸对血压正常盐敏感者肾血流动力学的影响

目的观察慢性盐负荷和左旋精氨酸对血压正常盐敏感者肾血流动力学的影响。方法以29例血压正常健康自愿者为研究对象,采用慢性盐负荷试验确定血压盐敏感性,观察盐敏感者和盐不敏感者在平衡饮食期、高盐饮食期及低盐饮食期的24h动态血压,同时监测肾小球滤过率（GFR）、有效肾血浆流量（ERPF）滤过分数（FF）及其在静点左旋精氨酸后的变化。结果29例血压正常健康自愿者中,检出盐敏感者（SS）11例（37．93％）,盐不敏感者（SR）18例;与平衡饮食期比较,ss组高盐负荷后ERPF显著减少、FF显著增加,输注左旋精氨酸后,仍存在上述改变;在平衡饮食期和高盐饮食期,SR组输注左旋精氨酸后较输注前ERPF显著增加,但SS组在输注左旋精氨酸前后ERPF无明显变化。结论血压正常盐敏感者高盐负荷时ERPF显著减少,FF显著增加,对左旋精氨酸反应迟钝,提示血压正常盐敏感者存在高盐介导的肾血管内皮功能异常。     

盐敏感性高血压与钠代谢及盐负荷后的肾排钠反应

用口服盐水负荷及速尿缩容试验相结合确定盐敏感者（ＳＳ），对人群中血压偏高青少年及高血压病人（ＥＨ）与血压正常对照者（ＮＴ）进行了年龄及性别配对研究。ＳＳ检出率在ＥＨ及高血压家族史阳性者中显著高于ＮＴ及高血压家族史阴性。ＳＳ血压值，夜尿钠量，血胰岛素水平等均明显升高，尿血管舒缓素排泄量减低，红细胞Ｎａ＋／Ｌｉ＋反转运增速。盐负荷后红细胞钠进一步升高，肾排钠反应呈现增强及减低两种类型，且后者的血浆肾素活性不被抑制，血压升高幅度亦大。提示盐敏感者有钠代谢缺陷，肾脏对盐负荷呈现调节及非调节两种类型。     

舒张性心力衰竭大鼠循环及组织交感活性与肾胺酶的相关性研究

目的研究舒张性心力衰竭大鼠模型血浆及心肌组织肾胺酶与交感神经递质多巴胺、肾上腺素、去甲肾上腺素的关系,探讨其在舒张性心力衰竭中的作用。方法采用腹主动脉和左侧肾动脉同时缩窄的方法建立大鼠舒张性心力衰竭模型,通过超声心动图监测和左心导管检查评价舒张性心力衰竭大鼠模型。研究血浆交感神经递质与肾胺酶之间的关系。结果术后12周成功建立舒张性心力衰竭大鼠模型。与假手术组比较,手术模型组大鼠血浆交感神经递质水平明显增高[其中多巴胺(15707.34±2 518.76)ng/ml比(7 731.34±1 162.59)ng/ml,P<0.01;肾上腺素(161.15±36.93)ng/ml比(61.72±13.84)ng/ml,P<0.01;去甲肾上腺素(141.06±50.98)pg/ml比(55.66±20.28)pg/ml,P<0.01],而肾胺酶水平明显降低[(9.33±5.46)pg/ml比(19.07±6.88)pg/ml,P<0.01]。相关分析表明循环肾胺酶与多巴胺、肾上腺素、去甲肾上腺素水平具有负相关关系(相关系数r分别为-0.640、-0.594、-0.528,均为P<0.05),而心肌组织肾胺酶与多巴胺、肾上腺素、去甲肾上腺素水平无明显相关性(相关系数r分别为0.584、0.474、0.194,均为P>0.05)。结论采用联合腹主动脉和左侧肾动脉同时缩窄的方法可以成功建立大鼠舒张性心力衰竭模型,此时肾胺酶在交感神经活性改变中发挥一定作用。     

盐敏感者盐负荷期间交感神经活性研究

为探讨盐敏感性个体交感神经活性与盐负荷的关系，对２３例２３～４０岁的血压正常者采用慢性盐负荷的方法确定盐敏感者（ＳＳ），观察盐负荷期间以及冷加压试验中血浆去甲肾上腺素（ＰＮＥ）和血浆肾上腺素（ＰＥ）水平、心率变异性、动态血压、２４小时尿Ｎａ＋排泄量和红细胞Ｎａ＋含量等变化。发现与盐不敏感者（ＮＳＳ）相比，ＳＳ者于盐负荷及应激状态下伴随血压的升高，ＰＮＥ和ＰＥ均增高，尤以ＰＮＥ为著；心率变异性频域分析中夜间低频（ＬＦ）和ＬＦ与高频（ＨＦ）成份比值（ＬＦ／ＨＦ）增加；动态血压中的夜间血压偏高，昼夜血压差值缩小。盐负荷期间２４小时尿Ｎａ＋排泄量降低，红细胞Ｎａ＋含量显著升高，且前者与ＰＮＥ呈负相关（ｒ＝－０．５４，Ｐ＜０．０５）。上述结果表明，本研究年龄段的血压正常盐敏感者存在高盐介导的交感神经活性增高表现。     

严格限盐对慢性肾小球肾炎患者血压及尿蛋白的影响

目的 评价严格饮食限盐对慢性肾小球.肾炎(CGN)患者血压及尿蛋白的影响.方法 选取2007年10月至2009年4月于北京大学第一医院肾内科住院且病情稳定的CGN患者32例,其中15例为试验组,17例为对照组,分别给予7 d严格限盐饮食(钠100 mmol/d,钾50 mmol/d,蛋白质0.8～1.0 g·kg~(-1)·d~(-1),热卡105～125 kJ·kg~(-1)·d~(-1))和医院普通饮食,应用24 h尿钠(24h-UNa)监测饮食钠摄入,观察两组患者血压、尿蛋白的变化.研究期间所有治疗维持不变.结果 入选时试验组24h-UNa为(135.1 4±50.4)mmol/d,与对照组(137.4 4±28.6)mmol/d 比较差异无统计学意义(P=0.743).试验组研究期间每天测定24h-UNa,为(97.2 ±8.6)mmol/d.限盐后患者收缩压由(117.7 ±10.0)mm Hg(1 mm Hg=0.133 kPa)降至(106.2 ±9.9)mm Hg(P<0.001),舒张压由(76.3 ±6.1)mm Hg降至(67.5 ±5.5)mm Hg(P<0.001),尿蛋自由1.57(0.3～3.0)g/d降至0.57(0.16～2.72)g/d(P=0.006).收缩压下降与尿钠减少呈正相关(r=0.572,P=0.026);尿蛋白减少与收缩压下降(r=0.568,P=0.027)及尿钠减少(r=0.525,P=0.044)均呈正相关.对照组仅收缩压由(122.6 ±15.5)mm Hg降低至(115.8 ±10.4)mm Hg(P=0.02),舒张压和尿蛋白呈下降趋势,但差异无统计学意义.两组中使用血管紧张素转换酶抑制剂和(或)血管紧张素Ⅱ受体拮抗剂的患者亚组比较显示,血压变化值无统计学差异,试验组尿蛋白的减少显著优于对照组[-0.4(-0.95～0.07)比0.07(-0.39～0.42),P=0.014].结论 严格饮食限盐有助于CGN患者更好地降低血压及尿蛋白.     

Carotid chemoreceptor reflexes following dietary salt loading in rats

There is a strong association between salt intake and hypertension. Alterations in baroreceptor activity, which precede and contribute to the elevation in blood pressure, have also been shown to affect chemoreceptor reflex response. Dietary salt loading with 8% sodium chloride was carried out in Sprague Dawley rats aged 8 weeks for a period of 5-6 weeks. Blood pressure was thereafter recorded under anaesthesia from the common carotid artery with a Grass Polygraph 7D model, whereas serum Na[Formula: See Text] and K[Formula: See Text] concentrations were measured using a flame photometer. Salt loading resulted in elevated arterial blood pressure as well as hypokalaemia. Stimulation of the carotid chemoreceptor by injection of sodium dithionite resulted in elevated arterial blood pressure, decreased heart rate and hyperventilation in both control and salt-loaded rats. However, the bradycardic response as estimated by the difference in percentage reduction in heart rate was significantly higher in salt rats (36%) than in the control rats (10%). The results indicate that a high-salt diet results in enhanced bradycardic response to carotid chemoreceptor stimulation and that this observation may be related to the attendant hypokalaemia.     

盐阈、盐摄入量与血压盐敏感性的关系研究

目的探讨盐阈、盐摄入量与血压盐敏感性之间的关系。方法选取203人进行慢性盐负荷试验,确定盐敏感性,并测定其盐阈、收集基线24h尿液,测定尿钠排泄量。结果盐敏感者检出率为19.2%。盐敏感与盐不敏感者之间盐阈、24小时尿钠排泄量差异无统计学意义;无论盐敏感者还是盐不敏感者,盐阈与24h尿钠排泄量有显著相关性。结论盐敏感者钠盐摄入量并不比盐不敏感者高;盐敏感者长期高盐饮食,才可能表现出盐与血压的联系,发生高血压。     

血压盐敏感者早期血管内皮功能改变研究

目的 盐敏感者较早出现靶器官功能损害,其心血管风险增加.本研究探讨血压正常或血压轻度偏高的盐敏感者血管内皮功能改变.方法 选99例年龄16～60岁、血压正常或血压轻度偏高者参与为期2周的慢性盐负荷试验,检测盐敏感性.试验包括基线3 d,低盐饮食、高盐饮食各7 d的研究.基线时采用彩色多普勒超声检测血流调节的血管扩张性,反映内皮依耐性血管舒张功能.试验各个阶段测量体重、血压,并收集血、尿标本.结果 盐敏感者检出率17.2%,盐敏感与盐不敏感者基线尿钠、钾排泄量无差异,而血浆NO浓度盐敏感者低于盐不敏感者[(61. 2±13.3)μmol/L比(82.5±14.6)μmol/L,P＜0.05];盐敏感者血流介导的肱动脉扩张性低于盐不敏感者[(10.2±2.5)%比(14.5±1.6)%,P＜0.05].结论 盐敏感者尽管尚处在血压正常或血压轻度偏高阶段已存在内皮功能损伤.

Abstract：

Objective Salt-sensitivity is associated with more severe target organ injury and higher mortality in patients with essential hypertension. We compared the vascular endothelial function between saltsensitive subjects(SS)and non-salt-sensitive subjects(NSS)with normal or mildly increased blood pressure. Methods Ninety-nine subjects(aged 16-60 years)with normal blood pressure or mild hypertension(degree 1)were enrolled. The test program included 3 days baseline investigation, 1 week lowsalt loading phase and 1 week high-salt loading phase. Endothelial function was assessed by measuring the flow mediated dilatation(FMD)of the brachial artery using high resolution ultrasound. Results There was 17. 2% SS. Plasma NOx level[(61.2 ± 13. 3)μmol/L vs(82. 5 ± 14. 6)μmol/L, P ＜ 0. 05]and FMD [(10.2±2.5)%vs(14.5 ± 1.6)%, P ＜0.05]were significantly lower in SS subjects than in NSS subjects. Conclusion Vascular endothelial dysfunction was evidenced in SS subjects with normal blood pressure or in the early stage of hypertension.     

青少年盐敏感者盐敏感性的远期可重复性及血压的增龄性改变

目的　观察青少年盐敏感性的可重复性 ,对比观察盐敏感与盐不敏感性青少年血压的增龄性改变。方法　 55名进行过急性盐水负荷和呋塞米缩容试验确定盐敏感性的青少年 ,于 5年后再次行静脉盐水负荷、呋塞米缩容试验 ,确定其盐敏感性的可重复性 ;比较 5年前、后均判定为盐敏感者的血压变化。结果　 (1 )静脉盐水负荷、缩容试验判定盐敏感性 5年后测定的可重复性为 92 7%。(2 )盐敏感组青少年 5年血压的增长值和增长幅度均高于盐不敏感组 ,分别为 9 9 4 7mmHg (1mmHg=0 1 33kPa)和 9 7 6 4个百分点 ,特别以收缩压最为显著 (P <0 0 1 )。结论　静脉盐水负荷试验确定盐敏感性具有良好的远期可重复性 ;青少年盐敏感者血压随年龄的增长幅度远高于盐不敏感者 ,特别是收缩压     

Association study of fasting blood glucose and salt sensitivity of blood pressure in community population: The EpiSS study

Background and aimsTo evaluate the association between fasting blood glucose (FBG) and salt sensitivity of blood pressure (SSBP).Methods and resultsThis study is based on the baseline survey of systemic epidemiology of salt sensitivity study. Subjects were classified into salt sensitive (SS) and salt resistant groups according to blood pressure (BP) changes during the modified Sullivan's acute oral saline load and diuresis shrinkage test. Multivariate logistic and linear regression were used to evaluate associations between FBG with SS or BP changes. A total of 2051 participants were included in the analyses with 581 (28.33%) for SS. Multiple analysis showed that for every interquartile range increase in FBG, the OR (95%CI) for SS was 1.140 (1.069, 1.215), β (95%CI) for mean arterial pressure change (ΔMAP₁), systolic and diastolic BP changes during saline load were 0.421 (0.221, 0.622), 0.589 (0.263, 0.914) and 0.340 (0.149, 0.531), respectively. Compared to the lowest FBG quartile (Q₁), the OR (95%CI) for SS in Q₃ and Q₄ were 1.342 (1.014, 1.776) and 1.577 (1.194, 2.084), respectively. Compared to subjects with normal FBG, the β (95%CI) for ΔMAP₁ was 0.973 (0.055, 1.891) in subjects with impaired FBG, and was 1.449 (0.602, 2.296) in patients with diabetes mellitus. Stratified analyses showed significant and stronger associations between FBG with SSBP in youngers, females, hypertensives, non-diabetics, non-current smokers and non-current drinkers.ConclusionOur findings suggest FBG is an independent, dose-dependent associated factor for SSBP, and prevention of SS focusing on controlling FBG elevation in the early stage is important.     

慢性盐负荷对血压盐敏感者血浆内皮生长因子C的影响

目的 本研究通过对正常血压受试者进行饮食干预试验,观察高盐对盐敏感者血浆内皮生长因子C(VEGF-C)的影响,探索淋巴系统在盐敏感性形成过程中的作用。方法对27例血压正常受试者进行7 d低盐、7 d高盐饮食干预,采用国际慢性盐负荷试验鉴别盐敏感者,筛选出盐敏感者9例,盐不敏感者18例,采用ELISA方法测定血浆VEGF-C的含量。结果两组受试者低盐期血浆VEGF-C水平比较无统计学差异〔(1921±238) mg/L vs.(1804±206) mg/L,P=0.59〕,而高盐干预后两组血浆VEGF-C水平均较低盐期明显增加〔盐敏感组(3642±406) mg/L,盐不敏感组(2249.8±214.6) μg/ml〕,并且高盐干预后盐敏感组VEGF-C水平较盐不敏感组显著升高（P<0.01）;相关分析表明,血浆VEGF-C水平与血压之间未发现具有统计学意义的相关性（r=0.412,P=0.29）。结论高盐饮食后盐敏感者体内VEGF-C显著升高,而VEGF-C可能成为盐敏感性识别的重要生化标记物之一。     

Potassium supplementation ameliorates increased plasma homocysteine induced by salt loading in normotensive salt-sensitive subjects

The mechanism by which high-salt and low-potassium diet contributes to hypertension remains poorly understood. Plasma homocysteine (Hcys) is recognized as a primary mediator of blood pressure (BP) response to some diets. Therefore, the present study tried to investigate whether plasma Hcys and BP could be regulated by salt loading in normotensive salt-sensitive (SS) persons, and further explored whether potassium supplementation could reverse the effect. We enrolled 47 normotensive subjects, aged 29–65 years. The protocol included 7 days on a low-salt diet (3g/day, NaCl), 7 days on a high-salt diet (18g/day), and then a high-salt diet with potassium supplementation (4.5g/day) for 7 days. After high-salt intake, BP was significantly increased and potassium supplementation lowered it in the SS group. Plasma Hcys were higher in SS subjects than in salt-resistant (SR) subjects after salt loading (34.4 ± 17.0 μmol/L versus 19.16 ± 6.4 μmol/L, P < 0.01). Plasma Hcys in SS subjects was increased on a high-salt diet than on a low-salt diet (34.4 ± 17.0 μmol/L versus 16.5 ± 8.3 μmol/L, P < 0.01), but plasma Hcys was ameliorated by potassium supplementation (34.4 ± 17.0 μmol/L versus 20.9 ± 10.4 μmol/L, P < 0.01). In SS subjects, the change of mean arterial blood pressure (MBP) correlated significantly and positively with the alteration of plasma Hcys during low-salt to high-salt intake and high-salt to high-salt with potassium supplementation (r = 0.75, P < 0.001; r = 0.74, P < 0.001, respectively). Our results indicate that Hcys may partly mediate the impact of high-salt intake and potassium supplementation on BP in SS subjects.     

Myocardial hypertrophy induced by high salt consumption is prevented by angiotensin II AT2 receptor agonist

Background and aims

Although many studies have reported the effects of AT1 receptor on dietary salt overload, the role of AT2 receptor in this model is far from completely elucidated. The present study aimed to better understand the role of AT2 receptor in cardiac structure alterations in response to chronic high salt intake in rats.