Blood oxygen transport and endothelial dysfunction in patients with arterial hypertension

Disturbed nitric oxide (NO) synthesis leads to development of endothelial dysfunction that plays a significant role in the pathogenesis of arterial hypertension. The presence of various compounds of haemoglobin with NO can affect haemoglobin-oxygen affinity of the whole blood. Methaemoglobin and S-nitrosohaemoglobin increase it, whereas nitrosyl-haemoglobin decreases. The aim of this study was to investigate the blood oxygen transport indices and to assess the endothelial function in patients with arterial hypertension. The patients with mild hypertension had a 4.47% increased actual p50 (the blood pO(2) corresponding to its 50% oxygen saturation) (P<0.05), a diminished pO(2) (P<0.05), and a raised pCO(2) (P<0.01) as compared with the controls. The patients with severe hypertension had decreased pO(2) and pH, and actual p50 was reduced by 3.03% (P<0.05), which reflects a more pronounced oxyhaemoglobin dissociation curve shift leftwards. These changes can be assessed as a blood oxygen transport decompensation that enhanced tissue hypoxia. The results of our studies indicate that the endothelial dysfunction in patients with arterial hypertension leads to significant impairments in blood oxygen transport indices. The endothelium may be involved in development of the above blood oxygen transport impairments, since only sufficient amounts of NO maintain a normal blood flow and oxygen transport to tissues. The endothelial dysfunction leads to a disturbed production of different haemoglobin NO derivatives, which not only affects NO release at different sites of the arterial bed, but also haemoglobin-oxygen affinity and optimal blood oxygenation and deoxygenation in capillaries. These data support the notion that endothelial dysfunction may alter haemoglobin-oxygen affinity and tissue oxygen supply in vivo. Alternation of haemoglobin-oxygen supply may be involved in the pathogenesis of hypertension.     

负荷量曲美他嗪对冠心病合并原发性高血压患者内皮功能的影响

目的观察曲美他嗪对冠心病合并原发性高血压患者血管内皮功能,指导临床用药。方法入选60例无糖尿病及高脂血症病史的冠心病合并原发性高血压患者,患者入院第3日病情平稳后检测血浆一氧化氮（NO）水平,并行肱动脉超声以检测血流介导的血管扩张变化率（flow-mediated dilation,FMD）。随后立刻顿服负荷量盐酸曲美他嗪片60 mg,并抽肘静脉血2 ml用以测定血浆NO水平。记录服药前后各项数据,并对数据行配对t检验。结果顿服负荷量曲美他嗪2小时后患者血浆NO水平明显高于服药前血浆NO水平,（49.33±9.84）μmol/L vs（48.15±11.35）μmol/L（P〈0.05）。顿服负荷量曲美他嗪2小时后患者FMD值明显高于服药前FMD值,（12.77±9.17）%vs（10.99±8.73）%（P〈0.05）。结论患者顿服负荷量曲美他嗪后血浆NO水平显著高于服药前,说明曲美他嗪对内皮细胞具有保护作用;患者顿服负荷量曲美他嗪后肱动脉FMD值显著高于于服药前,说明曲美他嗪能够改善血管内皮依赖性舒张功能;患者顿服负荷量曲美他嗪后未见不良反应。     

Erythrocyte organic phosphates and whole blood oxygen affinity in patients on continuous ambulatory peritoneal dialysis

Abstract. Whole blood oxygen affinity, erythrocyte pH and organic phosphates were studied in five anaemic untransfused patients with end stage renal disease undergoing continuous ambulatory peritoneal dialysis. Decreased whole blood oxygen affinity with increased adenosine triphosphate and normal 2.3 diphosphoglycerate (DPG) values were observed. Normal and stable serum phosphate and permanent mild metabolic acidosis may be important factors contributing to maintain DPG levels within the normal range despite anaemia. Continous dialysis avoids cyclic fluctuation of blood oxygen affinity as described during and after dialysis sessions in patients on maintenance haemodialysis.     

内皮型一氧化氮合酶基因多态性与2型糖尿病并发勃起功能障碍的相关性研究

目的探讨内皮型一氧化氮合酶（ecNOS）基因内含子4可变数目串联重复序列（4VNTR）插入／缺失多态性（4b／a）和外显子7单核苷酸多态性（G894T）与男性2型糖尿病（T2DM）并发勃起功能障碍（DED）的关联性。方法提取108例男性T2DM患者、94例DED患者及100例男性健康人（NC）的基因组DNA,用聚合酶链反应-可变数目串联重复序列法（PCR）测定4VNTR多态性;聚合酶链反应-限制片段长度多态性法（PCR-RFLP）测定G894T多态性。结果DED组吸烟史、糖尿病周围血管病变（DPA）均高于T2DM组（P〈0．01）;NC组、T2DM组、DED组3组低密度脂蛋白胆固醇（LDL-C）分别为（2．37±0．86）mmol／L、（2．85±0．74）mmol／L、（3．12±0．92）mmol／L,糖化血红蛋白（HbAlc）分别为（6．40±0．64）％、（5．06±1．09）％、（7．32±0．66）％（P〈0．05或〈0．01）;T2DM组、DED组甘油三酯（TG）和总胆固醇（TC）均高于NC组,TG为（1．76±0．66）mmol／L、（1．89±0．52）mmol／Lvs（1．35±0．54）mmol／L,TC为（4．95±0．77）mmol／L、（5．06±1．09）mmol／Lvs（4．31±0．86）mmol／L（均P〈0．01）;NC组、T2DM组、DED组3组间4VNTR多态性基因型（x^2=7．142,P=0．028）、等位基因（x^2=9．929,P=0．007）和G894T多态性基因型（x^2=2．118,P=0．002）、等位基因（x^2=15．468,P=0．000）频率分布差异均有统计学意义。logistic回归分析显示携带ecNOS4a等位基因（OR=2．282,P=0．012）、T等位基因（OR=5．217,P=0．002）以及合并DPA（OR=3．958,P=0．006）的T2DM患者并发DED的危险性更高。结论携带ecNOS基因内含子4a等位基因、894位点T等位基因以及合并DPA是男性T2DM并发DED的独立危险因素。     

β-blockers in the management of hypertension: focus on nebivolol

Hypertension is a major cardiovascular risk factor but most patients remain asymptomatic for many years. Successful therapy not only needs to be effective, it also needs to be well tolerated. β-blockers are well established as effective antihypertensive agents. However, one major drawback to the currently available β-blockers, particularly the noncardioselective β-blockers, is their side-effect profile, including sexual dysfunction, fatigue, depression and metabolic abnormalities such as impaired glucose tolerance and lipid abnormalities. Nebivolol (Bystolic^®), a novel, highly cardioselective, third-generation β-blocker that recently received approval by the US FDA for the treatment of hypertension in the USA, is effective in treating blood pressure and has a favorable side-effect profile. Studies conducted in Europe, where nebivolol has been available for some time for the treatment of hypertension, have shown that nebivolol achieves blood pressure reductions comparable to other β-blockers but with fewer side effects. Additionally, nebivolol has demonstrated similar efficacy in blood pressure reduction when compared with calcium channel blockers and inhibitors of the renin–angiotensin system. When combined with hydrochlorothiazide there was an additive antihypertensive effect. Lastly, nebivolol exhibits a vasodilatory property that is related to its effect on nitric oxide, an intrinsic vasodilator produced in the vascular endothelium. Nebivolol enhances nitric oxide bioavailablility. Studies have also demonstrated nebivolol’s ability to function as an antioxidant and decrease markers of oxidative stress. These effects are believed to ultimately produce a modulation of the endothelial dysfunction typically seen in hypertension.     

综合医院患者动脉血氧饱和度的研究

目的：了解临床送检动脉血标本的动脉血氧饱和度（ＳａＯ２）计算值和测定值的误差大小，以及用ＳａＯ２计算值指导临床实践是否可靠。方法：用临床各科送检的３１００份动脉血气标本测定值的有关数据，描绘动脉血氧分压（ＰａＯ２）血氧饱和度（ＳａＯ２）关系图及ＰａＯ２血氧含量（Ｏ２ＣＴ）关系图。结果：ＰａＯ２与ＳａＯ２的关系图不是单一的一条曲线，而是一个“Ｓ”形的区域带。当ＰａＯ２＝８．００ｋＰａ（１ｋＰａ＝７．５ｍｍＨｇ）时，ＳａＯ２变化范围为０．７２～０．９８；而当ＳａＯ２＝０．９０时，ＰａＯ２范围为６．００ｋＰａ～１２．２０ｋＰａ，实际半饱和氧分压（Ｐ５０）范围从２．１９ｋＰａ～１０．８８ｋＰａ，而ＰａＯ２与Ｏ２ＣＴ二者几乎无相关性。当ＰａＯ２＝８．００ｋＰａ时，Ｏ２ＣＴ范围为２．５４ｍｍｏｌ／Ｌ～９．１９ｍｍｏｌ／Ｌ，分布范围很大。结论：由ＰａＯ２和标准血红蛋白氧解离曲线推算ＳａＯ２、Ｏ２ＣＴ是不可靠的，ＳａＯ２必须直接测定     

大面积烧伤病人应用高氧液体的动脉血氧分压观察

目的 寻求改善烧伤患休克期全身缺氧的有效途径。方法 按患入院次序，将相同程度的烧伤患给预不同处理，输平衡盐油的30例对照组，输高氧液的30例为观察组。结果 大面积烧伤患输注高氧液后动脉氧分压逐渐升高，高于对照组，两组存在明显的差异。结论 静脉输注高氧医用液，有效改善全身缺氧，纠正酸中毒，有利于病人过休克期。     

阻塞性睡眠呼吸暂停综合征患者血管内皮功能损害和相关炎症因子的研究

目的探讨阻塞性睡眠呼吸暂停综合征（OSAHS）严重程度和血管内皮功能损害及相关炎症因子的关系。方法选择在本院呼吸科和心内科住院的0sAHS患者120例,并按0sAHs的严重程度分为轻度、中度和重度3组,分别测定3组患者的血管性血友病因子（vWF）、C反应蛋白（CRP）、白细胞介素6（IL-6）及一氧化氮（N0）的水平,并应用高频超声检测血管内皮功能的主要指标（肱动脉基础内径,反应性充血后肱动脉内径变化率,口服硝酸甘油后肱动脉内径变化率,峰值流速变化率）。结果重度OSAHS组的vWF、CRP、IL－6水平分别为（356．3±59．7）％、（35．54-15．2）mg／L、（41．2±8．5）ng／L明显高于中度的（248．7±51．3）％、（26．2±12．3）mg／L、（34．7±7．6）ng／L和轻度组的（135．8±48．6）％、（15．3±8．9）mg／L、（25．9±6．8）ng／L,中度组明显高于轻度组（P〈0．05）,而重度组反应性充血后肱动脉内径变化率、峰值流速变化率、NO平均水平分别（7．19±2．08）％、（46．86±9．98）％、（7．8±5．6）μmol／L明显低于中度组的（13．45±3．01）％、（54．26±10．05）％、（10．6±6．1）／μmol／L和轻度组的（21．10±2．25）％、（67．215±11．86）％、（15．6±7．3）μmol／L,中度组低于轻度组（P〈0．05）。结论0SAHS严重程度和血管内皮功能损害程度及其炎症因子密切相关。     

Different plasma levels of nitric oxide in arterial and venous blood

Experimental investigations suggest that a basal release of nitric oxide (NO) occurs in arterial but not in venous endothelium. We therefore decided to compare plasma levels of NO in the arterial and venous circulation. Parallel blood samples were drawn from the radial artery and brachial vein in 15 healthy drug-free women. Nitric oxide levels were assessed by measuring plasma levels of nitrite and nitrate, the two stable oxidation products of NO metabolism. Plasma levels of NO metabolites in arterial blood were significantly higher than in the paired venous blood samples (45·1 ± 17·7 versus 22·5 ± 8·5 μmol l^?1, respectively, mean ± SD). The results of this preliminary study strongly suggest that the endothelial release of NO is probably different in arteries and veins in vivo; this is also consistent with previous literature indicating that basal release of NO occurs mainly from the endothelium of arteries but not from that of veins.     

The use of haemoglobin glutamer-250 (HBOC-201) as an oxygen bridge in patients with acute anaemia associated with surgical blood loss

For the treatment of substantial blood loss in surgery, allogeneic blood is transfused to maintain stability and organ perfusion and function. Continued concerns about the availability, safety, efficacy and storage-related problems of allogeneic blood products have led to an intense effort to find alternatives that can serve the same physiologic functions. Haemoglobin-based oxygen carriers (HBOCs) are compounds that can match the oxygen-carrying capacity of red blood cells (RBCs), and several HBOCs have reached advanced stages of development and clinical testing. Multi-centre, randomised, Phase III, controlled trials have demonstrated the safety and efficacy of haemoglobin glutamer-250 (bovine) (Hemopure®, Biopure Corporation, Cambridge, MA, USA), also known as HBOC-201. HBOC-201 is bovine-derived, modified haemoglobin that has been ultrapurified to remove any plasma proteins, RBC stroma and potential pathogenic material. During the manufacturing process, crosslinking and polymerisation stabilise the haemoglobin molecule, which increases its vascular persistence as well as the efficiency of oxygen transport to tissue. Results from clinical trials indicate that HBOC-201 can be used as an oxygen ‘bridge’ for patients experiencing anaemia due to surgical blood loss, until their own red blood cells are replenished or have regenerated (haematinic effect). HBOC-201 is generally well-tolerated and is approved for use in South Africa, where it is indicated for use in adult surgical patients who are acutely anaemic, and is used to eliminate, delay or reduce the need for allogeneic RBCs. A Biologics License Application for HBOC-201 is currently under review by the US FDA.     

动脉血和混合静脉血的氧监测在心脏术后中的应用

目的　研究 37例心脏术后病人的动脉血和混合静脉血的氧监测的临床意义。方法　 37例病人分别于术后入ICU时 (术后Ⅰ组 )、术后 6～ 18h(术后Ⅱ组 )及术后 8～ 2 4h(术后Ⅲ组 ) ,测定动脉血pH值、氧分压 (PaO2 )、氧饱和度 (SaO2 )和混合静脉血pHv值、氧分压 (PvO2 )、氧饱和度 (SvO2 )及计算出氧利用率 (O2 ER)。结果　心脏术后病人的氧耗明显增加 (P <0 0 1) ,SvO2 与O2 ER呈明显的负相关 ,术后Ⅰ组、术后Ⅱ组及术后Ⅲ组的r值分别为 - 0 9198、- 0 92 6 0及 - 0 916 6 (P值均 <0 0 0 1)。结论　SvO2 是衡量心脏术后病人组织氧供需平衡的良好指标。     

高流量氧疗对AECOPD患者血气指标和膈肌功能的影响

目的研究高流量氧疗对慢性阻塞性肺疾病急性加重(AECOPD)患者血气指标和膈肌功能的影响。方法将2016年3月至2019年2月我院收治的110例AECOPD患者随机分为对照组(n=55,传统氧疗)和研究组(n=55,高流量氧疗)。比较两组的临床疗效。结果研究组再插管率低于对照组,咳痰困难、喘急胸闷消失率均高于对照组(P<0.05)。治疗后,两组PaO2、SaO2均升高,且研究组高于对照组(P<0.05)。治疗后,两组DEq、D-RSBI均降低,且研究组低于对照组(P<0.05)。结论与传统氧疗相比,高流量氧疗可有效减轻AECOPD患者咳痰困难、喘急胸闷,降低再插管率,改善血气指标,缓解膈肌疲劳。     

Pharmacological modulation of NO synthesis in patients with arterial hypertension and endothelial dysfunction

An open, comparative, cross-over 8-week trial of beta-blockers nebivolol and metoprolol in 30 patients with arterial hypertension (AH) studied the office, ambulatory blood pressure and heart rate levels, endothelium-dependent vasorelaxation, endothelial NOS and NO production. It was found that nebivolol activated the system eNOS-NO and improved vasomotor parameters of the endothelium. Metoprolol failed to activate enzyme eNOS activity and NO production to the same level and did not improve the endothelial vasomotor function. The antihypertensive activity of nebivolol was higher than that of metoprolol. Thus, nebivolol can be used in patients with AH and cardiovascular risk factors to correct endothelial dysfunction.     

贝那普利、地尔硫(艹卓)对心脏X综合征患者内皮功能的影响

目的 研究应用贝那普利、地尔硫(艹卓)对心脏X综合征(CSX)患者内皮功能的影响.方法 将40例CSX患者随机接受贝那普利(20例,贝那普利组)或地尔硫(艹卓)(20例,地尔硫(艹卓)组)治疗,并设20例健康人为对照组,比较治疗前及治疗12周后对一氧化氮(NO)、内皮素-1(ET-1)及对肱动脉内皮依赖性舒张功能的影响.结果 与正常对照组相比,CSX患者NO水平明显降低,ET-1水平明显升高,血管内皮依赖性舒张功能受损(均P＜0.01).用药后贝那普利组较用药前NO明显升高(54.15±19.48)μmol/L vs(70.25±17.46)μmol/L(P＜0.01),地尔硫(艹卓)组用药后NO明显升高(55.69±16.32)μmol/L vs(59.17±14.92)μmol/L(P＜0.05).ET-1明显降低(70.61±6.22)ng/Lvs(55.18±4.71)ng/L(P＜0.01),血管内皮依赖性舒张功能改善(4.60±2.40)%vs(10.60±2.50)%(P＜0.01),地尔硫(艹卓)组较用药前ET-1明显降低(69.37±7.85)ng/L vs(62.94±6.38)ng/L(P＜0.05),血管内皮依赖性舒张功能改善(4.70±2.30)%vs(6.40±1.90)%(P＜0.05).结论 CSX患者存在血管内皮功能障碍,贝那普利与地尔硫(艹卓)均能改善CSX患者的内皮功能,且较地尔硫(艹卓)更为有效.     

原发性高血压及高血压合并高胆固醇血症血管内皮功能的超声研究

目的 探讨原发性高血压及高血压合并高胆固醇血症患者血管内皮依赖性舒张功能的改变。方法 采用彩色多普勒高频超声的间歇成像和能量多普勒成像，对24例原发性高血压患者（EH组）、24例高血压合并高胆固醇血症患者（EH＋HC组）及24例正常血压、血胆固醇者（NT组）的血管内皮依赖性舒张功能，包括静息时血管内径（BD）、增加流量引起的血管舒张（FMD）、服用硝酸甘油引起的血管舒张（GTN）等，以及对血浆一氧化氮（NO）、内皮素（ET）、血栓素B2（TXB2）和前列腺环素（PGI2）等血管活性物质进行检测并比较分析。结果 EH和EH＋HC组反应性充血引起的FMD值明显减弱，与NT组比较差异有非常显著性（均P〈0．01），EH与EH＋HC组之间比较差异亦有统计学意义（P〈0．05）；含服硝酸甘油后肱动脉内径明显扩张，但各组间GTN值差异无统计学意义（P〉0．05）；EH＋HC、EH组与NT组比较血浆中NO、PGI2水平明显降低，而ET、TXB2水平明显升高（均P〈0．01），EH＋HC与EH组间比较差异亦有统计学意义（P〈0．05）。结论 高血压患者存在血管内皮依赖性舒张功能受损，高血压合并高胆固醇血症时，内皮功能受损进一步加重。彩色多普勒超声是评价血管内皮舒张功能的简单、无创且可靠方法。     

Methodological aspects of the evaluation of endothelium-dependent vasodilatation in the human forearm

The present study, involving 56 healthy subjects from a health screening, was undertaken to address some methodological questions regarding the measurement of endothelial function using local intra-arterial infusions of metacholine (2 and 5 μg min^?1) to evaluate endothelium-dependent vasodilatation, and sodium nitroprusside (SNP, 5 and 10 μg min^?1) to evaluate endothelium-independent vasodilatation. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The ratio of FBF during the highest dose of metacholine to FBF during the highest dose of SNP was used as an index of endothelial function. In 10 young volunteers the procedure was repeated after 2 h and again after 3 weeks in order to study short-term and long-term reproducibility of the method. Neither the vasodilatatory response to metacholine (r = 0·006) nor that to SNP (r = 0·08) was related to resting FBF. Neither the circumference nor the length of the arm was related to endothelial function (r = 0·01?0·11), as evaluated by the FBF on metacholine to nitroprusside ratio (mean 1·3 ± 0·3 SD). The use of a wrist cuff to exclude hand circulation, or not, did not influence the evaluation of endothelial function significantly. Maximal FBF after 3 min of arterial occlusion of the forearm was significantly related to blood flow during both metacholine (r = 0·53, P < 0·01) and nitroprusside infusion (r = 0·36, P < 0·05), but not to the FBF on metacholine to nitroprusside ratio (r = 0·01). The short-term and long-term reproducibility of FBF during vasodilatation with metacholine and SNP was good (r = 0·89?0·97, P < 0·001), while the individual measurements for resting FBF were less reproducible when repeated after 3 weeks (r = 0·34). In conclusion, endothelial function was not related to resting FBF, nor to the arm circumference or length. No major difference was seen whether endothelial function was evaluated with or without exclusion of the hand circulation. Maximal FBF during reactive hyperaemia was not related to endothelial function.     

Desmopressin (DDAVP) induces NO production in human endothelial cells via V2 receptor- and cAMP-mediated signaling

Summary.  The hemostatic agent desmopressin (DDAVP) also has strong vasodilatory effects. DDAVP is a selective agonist for the vasopressin V2 receptor (V2R), which is coupled to cAMP-dependent signaling. DDAVP-induced vasodilation may be due to endothelial NO synthase (eNOS) activation. This hypothesis implies cAMP-mediated eNOS activation. It also implies wide extrarenal, endothelial V2R expression. We show that in human umbilical vein endothelial cells (HUVECs) the cAMP-raising agents forskolin and epinephrine increase NO production, as measured by a l -NMMA-inhibitable rise in cellular cGMP content. They also increase eNOS enzymatic activity, in a partly calcium-independent manner. cAMP-mediated eNOS activation is associated with phosphorylation of residue Ser1177, in a phosphatidyl inositol 3-kinase (PI3K)-independent manner. HUVECs do not express V2R. However, after heterologous V2R expression, DDAVP induces cAMP-dependent eNOS activation via Ser1177 phosphorylation. We have previously found V2R expression in cultured lung endothelial cells. By real time quantitative RT-PCR, we now find a wide V2R distribution notably in heart, lung and skeletal muscle. These results indicate that DDAVP and other cAMP-raising agents can activate eNOS via PI3K-independent Ser1177 phosphorylation in human endothelial cells. This mechanism most likely accounts for DDAVP-induced vasodilation.     

运动训练对高血压患者血压、内源性一氧化氮及内皮素的影响

目的：明确原发性高血压病患者的运动康复与血压、血一氧化氮、内皮素水平变化的关系。方法：62例原发性高血压病患者，分为训练组(n=51)和对照组(n=11)。训练组进行为期7周，每周6次，每次1小时的轻、中度运动训练。结果：训练组患者运动后血压、血一氧化氮、内皮素水平均显著下降。对照组无明显变化。结论：在原发性高血压患者的运动康复中血一氧化氮、内皮素水平有明显改变。     

替格瑞洛与氯吡格雷对冠心病患者血管内皮功能的影响

目的 临床试验及研究已经初步证实P2Y12受体阻滞剂可改善血管内皮细胞功能.本研究探讨替格瑞洛和氯吡格雷在改善血管内皮功能方面作用.方法 选取就诊于我院心内科住院诊治的80例急性冠状动脉综合征(ACS)并行经皮冠状动脉介入治疗(PCI)的患者.将入选患者按1:1比率随机分为2组,其中替格瑞洛组(n=40)予以替格瑞洛9...