H型高血压合并冠心病患者外周血中EMMPRIN、ADMA、Hcy、MMPs、Treg和Th17细胞水平检测

目的探讨H型高血压合并冠心病患者进行外周血各细胞因子水平检测的意义 方法选取陆军军医大学第一附属医院2015年5月至2018年2月收治的84例高血压合并冠心病患者作为观察组,其中H型高血压合并冠心病患者42例,归为H组,非H型高血压合并冠心病患者42例,归为非H组。随机选取同期我院收治的50例未合并高血压的冠心病患者为冠心病组,50例未合并冠心病的高血压患者为高血压组,45名健康成人为对照组。比较各组外周血EMMPRIN、MMPs、ADMA、Hcy、Treg、Th17细胞水平。采用方差分析和q检验进行统计学分析。 结果H组、非H组、冠心病组、高血压组患者外周血细胞外基质金属蛋白酶诱导因子（EMMPRIN）、基质金属蛋白酶（MMPs）、不对称二甲基精氨酸（ADMA）、Hcy、Th17细胞含量均高于对照组,Treg细胞含量与Treg/Th17的比值低于对照组（P?< 0.05）。H组患者血浆ADMA[（11.01±2.67）μmol/L]、Hcy含量[（17.78±3.32）μmol/L]高于非H组[（7.34±1.34）μmol/L、（6.26±2.17）μmol/L]、冠心病组[（9.11±2.28）μmol/?L、（7.39±3.09）μmol/L]、高血压组[（8.89±1.89）μmol/L、（6.89±2.38）μmol/L],差异有统计学意义（F?= 13.360,8.961,P?< 0.05）。而H组、非H组、冠心病组、高血压组患者外周血单核细胞表面的EMMPRIN表达量、MMPs、Treg细胞、Th17细胞含量与Treg/Th17的比值比较,差异均无统计学意义（P?> 0.05）。 结论H?型高血压合并冠心病患者外周血中EMMPRIN、MMPs、ADMA、Hcy水平升高,Treg/?Th17比值降低,其中ADMA的升高与H型高血压有相关性。     

Alteration of erythrocyte membrane Na,K-ATPase in children with borderline or essential hypertension

The aim of this study was to evaluate the substrate (ATP) kinetics of erythrocyte membrane Na, K-ATPase in children with borderline or essential hypertension. Although the activity of Na, K-ATPase in the presence of in vivo concentrations of ATP was not significantly altered, kinetic studies showed an obvious inhibition of enzyme activity in the erythrocyte membrane of children with borderline or essential hypertension. Hanes plot analysis revealed a decrease of V_max from 7·19 in erythrocytes from control subjects to 4·93 and 3·33 in those from children with borderline or essential hypertension, respectively. A mean value of the K_m decreased from 0·10 in the control to 0·08 and 0·02 in children with borderline or essential hypertension, respectively. The energy status of erythrocytes, estimated by ATP, ADP and AMP levels, ATP/ADP ratio, and adenylate energy charge (AEC) was not significantly changed in the cells from hypertensive children. The use of a free radical-generating system (FeSO₄/ascorbate) in vitro significantly reduced enzyme activity in the control erythrocytes while in those from hypertensive children it was abolished completely. The level of lipid peroxides was considerably higher (+37 per cent) in the plasma, while that of reduced glutathione was significantly lower both in the erythrocytes and the plasma of children with essential hypertension than in healthy children. These results indicate significant alterations of the antioxidant status which could be the cause of the inhibited Na,K-ATPase activity in erythrocyte membranes from hypertensive children.     

Docosahexaenoic acid, but not eicosapentaenoic acid, lowers ambulatory blood pressure and shortens interval QT in spontaneously hypertensive rats in vivo

This study was designed to evaluate the effects of individual dietary long-chain n-3 polyunsaturated fatty acids (LCPUFA) on hypertension and cardiac consecutive disorders in spontaneously hypertensive rats (SHR) as compared to Wistar-Kyoto rats (WKY). Rats were fed for 2 months an eicosapentaenoic (EPA)- or docosahexaenoic acid (DHA)-rich diet (240 mg/day) or an n-3 PUFA-free diet. Male SHR (n=6), implanted with cardiovascular telemetry devices, were housed in individual cages for continuous measurements of cardiovascular parameters (blood pressure (BP) and heart rate (HR)) during either activity or rest periods, ECG were recorded during the quiet period. The n-6 PUFA upstream of arachidonic acid was affected in SHR tissues. The cardiac phospholipid fatty acid profile was significantly affected by dietary DHA supply, and EPA in a very lower extent, since DHA only was incorporated in the membranes instead of n-6 PUFAs. Endothelium n-6 PUFA content increased in all SHR groups. Compared to WKY, linoleic acid content decreased in both studied tissues. Cardiac noradrenalin decreased while the adrenal catecholamine stores decreased in SHR as compared to WKY. Both n-3 PUFA supply induced a decrease of adrenal catecholamine stores. Nevertheless after 6 weeks, DHA but not EPA induced a lowering-blood pressure effect and shortened the QT interval in SHR, most probably through its tissue enrichment and a specific effect on adrenergic function. Dietary DHA supply retards blood pressure development and has cardioprotective effect. These findings, showing the cardioprotective effects of DHA in living animals, were obtained in SHR, but may relate to essential hypertension in humans.     

Long-term efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension

Background. Inoperable chronic thromboembolic pulmonary hypertension (CTEPH) is associated with a poor survival. Objectives. To evaluate the long-term response to a dual endothelin receptor antagonist in patients with inoperable CTEPH. Methods. All consecutive 18 patients (mean age 63±14 years) treated with bosentan for symptomatic inoperable CTEPH were included. Efficacy was evaluated by the log value of serum levels of N-terminal-pro brain natriuretic peptide (log NTpro BNP), New York Heart Association functional class (NYHA), and the six-minute walk test (6-MWT). All follow-up data (median 31 months) were compared with baseline and divided into: short-term (<12 months), mid-term (between 12 and 24 months), and long-term follow-up (>24 months). Results. At baseline, 15 patients were in NYHA class III and three in NYHA class IV, mean log NT-pro BNP level was 7.2±1.4 log pg/ml, and mean 6-MWT distance was 404±125 m. During short-term follow-up (n=18), the NYHA class improved (p=0.001), 6-MWT distance increased by 33 m (p=0.03), and log NT-pro BNP decreased to 6.9±1.4 log pg/ml (p=0.007). During mid-term follow-up (n=17), the NYHA class improved (p<0.001), the mean 6-MWT distance increased by 41 m (p=0.01), and log NT-pro BNP was 6.9±1.4 log pg/ml (p=0.31). During late followup (n=14) the NYHA class was still improved (p=0.03), the 6-MWT distance decreased by 9 m (p=0.73), and log NT-pro BNP was 7.1±1.5 log pg/ml (p=0.91). The overall four year survival rate was 88%. Conclusion: Bosentan seems to be effective during long-term treatment in patients with inoperable CTEPH. (Neth Heart J 2009;17:329–33).     

Bosentan in pulmonary arterial hypertension: a comparison between congenital heart disease and chronic pulmonary embolism

Background. In patients with pulmonary hypertension, it is unknown whether the treatment effect of bosentan is dependent on the duration of pulmonary vessel changes. Therefore, we studied the response to bosentan in patients with life-long pulmonary vessel changes (pulmonary arterial hypertension (PAH) due to congenital heart disease (CHD)) and in patients with subacutely induced pulmonary vessel changes (chronic thromboembolic pulmonary hypertension (CTEPH)). Methods. In this open-label study, 18 patients with PAH due to CHD and 16 patients with CTEPH were treated with bosentan for at least one year. All patients were evaluated at baseline and during follow-up by means of the six-minute walk distance (6-MWD) and laboratory tests. Results. Improvement of 6-MWD was comparable in patients with PAH due to CHD (444±112 m to 471±100 m, p=0.02), and in CTEPH (376±152 m to 423±141 m, p=0.03) after three months of treatment. After this improvement, 6-MWD stabilised in both groups. Conclusion. Although duration of pulmonary vessel changes is strikingly different in patients with PAH due to CHD and CTEPH, the effect of one year of bosentan treatment was comparable. The main treatment effect appears to be disease stabilisation and decreasing the rate of deterioration. (Neth Heart J 2009;17:334–8.)     

Neonatal intermittent hypoxia and hypertension

Obstructive apnea during sleep is accompanied by intermittent hypoxia (IH) leading to hypertension and other cardiovascular disturbances. A comparative evaluation of long-term effects of the neonatal IH on the cardiovascular functions was performed in normotensive Sprague-Dawley and spontaneously hypertensive rats (SHR). The newborn rats were placed for 30 days to conditions of IH (8% and 21% O₂, alternating every 90 s for 12 h/day). Control groups of rats were constantly kept in normoxia. By 6 months, in the spontaneously hypertensive rats exposed to IH at the period of wakefulness there was a statistically significant increase (as compared with control) of the systolic (185.8 ± 1.7 and 169.9 ± 1.4 mm Hg, correspondingly, p < 0.010 and the diastolic pressure (96.2 ± 4.9 and 86.0 ± 2.6 mm Hg, correspondingly, p < 0.01). During sleep, the systolic and diastolic pressure in these rats was higher than in control animals by 10 mm Hg (p < 0.01) and 12 mm Hg (p < 0.01), its decrease during sleep being absent. In SHR submitted to IH there was an increase in the power ratio of the heart rate variability from 0.9 ± 0.15 to 1.5 ± 0.17, which indicates a shift of the sympathico-parasympathetic balance in this group towards predominance of the sympathetic component. In the Sprague-Dawley rats exposed to neonatal hypoxia, the above-indicated changes were not prominent. These peculiarities of the hypertensive rats allow establishing connection of the genetic factor with the sympathetic mechanism providing long-term consequences of the neonatal IH for the cardiovascular control in the SHR.     

BKCa增龄变化及其与血压的相关性

目的：探讨大电导钙激活钾通道（BKCa,MaxiK）增龄变化及其与血压水平的关系。方法：选取雄性9、15、21、27、33周龄自发高血压大鼠（SHR）及对照组正常血压大鼠（WKY）,每周龄两类大鼠各4只;测定各周龄SHR和WKY的腹主动脉血压;分离肠系膜小动脉及其血管平滑肌细胞;利用膜片钳全细胞模式记录肠系膜小动脉VSMCs钾电流、用四乙胺（TEA）阻断BKCa后的电流、膜电容,以计算BKCa电流值、BKCa电流密度;探讨BKCa电流密度增龄变化与血压的关系。结果：SHR肠系膜小动脉血管平滑肌细胞（VSMCs）BKCa电流密度随增龄降低,而WKY随增龄的变化无统计学意义（P〉0．05）;SHR肠系膜小动脉VSMCs BKCa电流密度与腹主动脉MABP高度相关（r=-0．7174）,而WKY肠系膜小动脉VSMCs BKCa电流密度与腹主动脉MABP低度相关（r=-0．4832）。结论：BKCa电流和电流密度随增龄衰减,血压水平是衰减程度的重要反应;BKCa电流密度与血压水平高度相关。     

Two decades with dimorphic Chloride Intracellular Channels (CLICs)

Plasma membrane channels have been extensively studied, and their physiological roles are well established. In contrast, relatively little information is available about intracellular ion channels. Chloride Intracellular Channel (CLICs) proteins are a novel class of putative intracellular ion channels. They are widely expressed in different intracellular compartments, and possess distinct properties such as the presence of a single transmembrane domain, and a dimorphic existence as either a soluble or membranous form. How these soluble proteins unfold, target to, and auto-insert into the intracellular membranes to form functional integral ion channels is a complex biological question. Recent information from studies of their crystal structures, biophysical characterization and functional roles has provoked interest in these unusual channels.     

α1-烟碱样乙酰胆碱受体在门脉高压症发病机制中的作用分析

目的:探讨肝组织中的α1-烟碱样乙酰胆碱受体在胆汁性肝纤维化引起的门静脉高压症(PHT)发病机制中的作用。方法:取体重240-260g的清洁级雄性SD大鼠30只,根据体重随机分为假手术组、模型组。模型组采用胆总管结扎术(CBDL)对大鼠进行造模,分别于2周、4周测门静脉压力,并用免疫组化和免疫印迹法对α1-烟碱样乙酰胆碱受体(nAchRα1)进行定位及定量的检测。结果:假手术组的门静脉压力是7.97±0.55mmHg,造模后2周和4周门静脉压力升高,分别为14.15±0.92mmHg;17.75±0.86mmHg。免疫组化显示nAchRα1主要表达在肝窦和汇管区。免疫印迹显示模型组nAchRα1的表达较假手术组明显增多。结论:nAchRα1可能通过活化肝星状细胞,进而形成肝窦毛细血管化,来参与门静脉高压症的发病机制。     

Role of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) in the regulation of blood pressure by leptin in lean and obese rats

We investigated the role of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in hemodynamic action of leptin. The effect of leptin (1 mg/kg i.p.) on systolic blood pressure (SBP) was examined in lean rats and in rats made obese by feeding highly palatable diet for either 1 or 3 months. Separate groups received NO synthase inhibitor, L-NAME, or EDHF inhibitors, the mixture of apamin+charybdotoxin or sulfaphenazole, before leptin administration. Leptin increased NO production, as evidenced by increase in plasma and urinary NO metabolites and cyclic GMP. This effect was impaired in both obese groups. In lean rats either leptin or EDHF inhibitors had no effect on blood pressure. L-NAME increased blood pressure in lean animals and this effect was prevented by leptin. However, when leptin was administered to animals pretreated with both L-NAME and EDHF inhibitors, blood pressure increased even more than after L-NAME alone. In the 1-month obese group leptin had no effect on SBP, however, pressor effect of leptin was observed in animals pretreated with EDHF inhibitors. In the 3-month obese group leptin alone increased SBP, and EDHF inhibitors did not augment its pressor effect. The results suggest that leptin may stimulate EDHF when NO becomes deficient, e.g. after NOS blockade or in short-term obesity. Although the effect of leptin on NO production is impaired in the 1-month obese group, BP does not increase, probably because EDHF compensates for NO deficiency. In contrast, leptin increases BP in 3-month obesity because its effect on EDHF is also attenuated.