血管外膜源性舒张因子的作用机制

目的： 验证血管外周脂肪组织释放血管外膜源性舒张因子(ADRF)，并对ADRF的作用机制做初步探讨。方法：检测WKY大鼠带完整血管外周脂肪组织的血管环和不带血管外周脂肪组织的裸血管环的收缩力；并用液体转移方法鉴证血管外周脂肪组织释放ADRF，使用工具药对ADRF作用途径进行观察。结果：与配对裸血管相比，带完整血管外周脂肪组织的胸主动脉在苯肾上腺素(PHE,10-6 mol/L)诱发的血管收缩力下降20.5%；把孵育带完整血管外周脂肪组织的胸主动脉的生理池液体转移到配对裸血管，引起裸血管舒张20.8%；在无钙液中，有无血管外周脂肪组织的血管之间PHE诱发的收缩力无区别；钙激活的钾通道 (K_Ca)阻断剂四乙胺和ATP敏感性钾通道（K_ATP）阻断剂格列苯脲均有效阻断ADRF的血管舒张作用。结论：血管外周脂肪组织释放一种引起血管舒张的ADRF，ADRF通过激活K_Ca、K_ATP发挥作用，且需钙离子参与。     

缬沙坦对血管内皮舒张功能的影响

目的探讨缬沙坦对高血压病人血管内皮依赖性舒张功能的影响.方法观察35例高血压病人服缬沙坦前后和32例正常血压对照者在反应性充血时和含服硝酸甘油后肱动脉的内径变化.结果高血压组血流介导的肱动脉舒张和硝酸甘油所致的肱动脉舒张均低于对照组[分别为(3.61±2.88)%比(9.13±5.49)%和(15.10±6.76)%比(21.63±7.35)%,P＜0.01].高血压病人服缬沙坦后血流介导的肱动脉舒张和硝酸甘油所致的肱动脉舒张测定值为(8.27±4.42)%和(19.74±7.06)%,较服药前明显改善(P＜0.01).结论高血压病人内皮依赖性及非内皮依赖性的血管舒张功能均受损.缬沙坦对血管内皮依赖性舒张功能有改善和保护作用.     

血管内皮依赖性超极化因子

血管内皮细胞释放的血管舒张因子除一氧化氮和前列腺素外 ,尚可能存在着第三种因子 ,即内皮依赖性超极化因子。这种因子可引起平滑肌膜电位的超极化和舒张 ,其作用不能被一氧化氮合酶和环氧酶抑制剂阻断 ,但可被钾通道阻断剂抵抗。内皮依赖性超极化因子的化学本质目前尚不清楚。     

超声检测高血压病人血管内皮依赖性舒张功能

目的 采用Ｃｅｌｅｒｍａｊｅｒ等的方法对照观察高血压（ＥＨ）患者在休息时,反应性充血,再休息以及含服硝酸甘油后肱动脉内径向血流的变化,以介高血压患者血管内皮依赖性舒功能的变化。方法 采用高分辨超声技术,对５１例ＥＨ患者和３５例正常对照者的血管内皮依赖性舒张功能进行测定评价,并测定其血浆一氧化氮（ＮＯ）,内皮素（ＥＴ）血栓素Ｂ２（ＴＸＢ２）和前列腺环素（ＰＧＩ２）等血管活性物质的浓度变化。结果 发现     

美蓝与消炎痛对高血压大鼠内脏血管内皮依赖性舒张减弱的影响

本文应用双标本微量生物测定法观察自发高血压大鼠（ＳＨＲ）及其常压对照（ＷＫＹ）大鼠肠系膜动脉Ａｃｈ内皮依赖性舒张（ＥＤＲ）的变化，并对其机制进行初步探讨，结果发现：ＳＨＲ的ＡｃｈＥＤＲ显著弱于ＷＫＹ者；鸟苷酸环化酶抑制剂美蓝（５×１０－５ｍｏｌ／Ｌ）可明显减弱ＳＨＲ与ＷｋＹ的ＡＣｈＥＤＲ，此时ＳＨＲ的舒张仍明显弱于ＷＫＹ。灌流消炎痛（５×１０－５ｍｏｌ／Ｌ）后，卒中易感型自发高血压大鼠（ＳＨＲｓｐ）的ＡｃｈＥＤＲ增强，ＷＫＹ的舒张反应几乎不变。此时ＳＨＲｓｐ与ＷＫＹ的肠系膜动脉的ＡｃｈＥＤＲ的差异消失。以上结果支持高血压的内脏血管ＥＤＲ减弱的结论，并且可以认为乙酰胆碱（Ａｃｈ）激发的血管内皮舒张因子（ＥＤＲＦ）通过ｃＧＭＰ环节的功能发生变化。以及血管内皮细胞释放的收缩因子（ＥＤＣＦ）增多是这一减弱的原因之一。     

红细胞源降压因子对糖尿病性高血压大鼠血管的保护作用

探讨红细胞源降压因子 (EDDF)对糖尿病性高血压大鼠血管的保护作用。实验用Wistar大鼠 ,随机分为对照组 (n =9)和糖尿病模型组 (n =9)。用尾动脉脉压法测定血压 ;用血管环生物灌流法检测EDDF对血管的舒张作用 ;用透射电镜观察EDDF对肾脏阻力血管的超微结构。结果表明 ,糖尿病大鼠血糖、血压比对照大鼠均明显升高。口饲EDDF(10 0mg/kg)可显著降低糖尿病性高血压大鼠的血压。给药前后的血压分别为 (135 7± 3 0 )对比 (119 7±2 0mmHg) (1mmHg=133 32 2Pa) (P <0 0 1) ,而EDDF对正常大鼠的血压无明显影响 [(118 8± 2 0 )对比 (116 5±2 7mmHg) ];EDDF (10 -4g/mL)对两组大鼠肠、肾和脑的阻力血管均有明显的舒张作用 (P <0 0 5 ) ;在透射电镜下观察到EDDF可以明显改善糖尿病性高血压大鼠异常的肾脏阻力血管VSMCs的超微结构。EDDF对伴有高血压的糖尿病大鼠具有明显的降压作用 ,其作用机制可能与舒张中枢、外周小血管 ,保护肾血管超微结构密切相关     

钾通道TREK-1介导的局部血管舒张调节研究进展

TREK-1（TWIK—Related K^＋Channel 1）是K2P通道（Two—Pore-Domain Potassium Channels）家族的重要成员,可以被机械刺激、脂质分子、细胞膜内外H^＋等有效激活。早期对TREK-1的表达与功能研究多集中于神经元,近年研究表明TREK-1表达于内皮细胞并介导局部血管舒张调节,     

高血压患者血管内皮依赖性舒张功能失调的研究

目的 :观察不同程度高血压对血管内皮依赖性舒张功能失调的影响 ,并探讨其发生的可能机制。方法 :71例原发性高血压患者按照高血压程度分为Ⅰ、Ⅱ、Ⅲ级三组。另设正常血压对照组 3 0例。采用高分辨超声影像技术 ,测量肱动脉反应性充血前后血管内径和血流速度的变化。测定各组受试者反应性充血前后血浆NO、PGI2 、TXB2 、ET等血管活性物质。结果 :随高血压分级程度增加 ,肱动脉血管内皮依赖性舒张能力逐步变小 ,血浆NO、PGI2 逐渐下降 ,TXB2 、ET逐渐增高。结论 :随着高血压程度的加重 ,血管内皮依赖性舒张功能受损也加重 ,可能是由于内皮源性NO、PGI2 等舒张性因子合成释放减少而缩血管因子ET、TXB2 合成释放增加有关。     

两种新的血压调节物质—高血压因子与抗高血压因子研究进展

血压调节是一个十分复杂的生理过程,它除了有快速而短暂的神经调节和缓慢而持久的体液调节外,血管还始终发挥着自身的调节作用。高血压病的发生和发展主要是血压长期调节的紊乱,致使小动脉张力持续升高所致。其中体液因素具有重要作用。其证据是:(1)交叉灌流实验发现高血压动物的体液中存在着可以使正常动物血压升高的物质,例如将高血压动物的血浆注射到正常动物,可使后者许多组织细胞内钙离子(Ca~(2+)浓度升高,胞膜Na~+,K~+-ATP酶活性降低;(2)与自发性高血压大鼠(SHR)联体并生的正常大鼠也出现了在SHR观察到的许多现象,如血管反应性升高等;(3)近年来Wright及McCumbee等从SHR的红细胞及其他组织中提取出高血压因子及随后发现的抗高血压因子更证明了这一点。本文简要综述这两种新发现的血压调节物质的研究进展。     

脑源性神经营养因子对血管新生的作用

脑源性神经营养因子（brain—derived neurotrophic factor,BDNF）是神经营养因子家族的一员,对中枢和外周神经系统多种类型神经元的生长、发育、分化和再生具有重要作用。研究显示人脐静脉内皮细胞（HUVEC）、人脑血管内皮细胞等多种内皮细胞以及新生血管平滑肌细胞均能产生BDNF,而且BDNF对血管内皮细胞的生长发育起着重要的支持作用。因此我们推测BDNF可能在一定程度上参与了机体新生血管的形成。为此,我们对BDNF的体内体外促血管新生作用进行了研究。     

血管平滑肌钾通道与原发性高血压

Essential hypertension(EH)is characterized by an increased total peripheral resistance.There are four types of potassium channels in vascular smooth muscle cells,including Kca,Kv,Kir,KATP,which play an important role in regulating the diameter of vascular.The change of potassium channels may have something to do with the pathogenesis of hypertension.This article reviews the characters of potassium channels and their roles in EH.     

内皮依赖性超极化因子的研究进展

Until now,although the molecule of EDHF has not been cloned,some characteristics of EDHF has been clarified by scientists.It is different from NO and prostacyclin,and it is considered to play an important role in the regulation of vascular tone by stimulating the channels of K^ d and Ca^2 .     

Membrane rectification in single smooth muscle cells from the rat tail artery

Membrane rectification to depolarization was studied by voltage recording with patch electrodes in freshly isolated cells from the rat tail artery. Injection of depolarizing currents elicited electrotonic potentials that developed with a single-exponential time course (time constant of 94.8 ms). When the cell was depolarized beyond –30 mV, delayed rectification was observed. A second type of rectification, characterized by oscillations, was observed when the cell was depolarized positive to + 30 mV. The threshold of this rectification and the oscillations were sensitive to changes in intracellular Ca²⁺. Delayed rectification was more sensitive to 4-aminopyridine but more resistant to tetraethylammonium and charybdotoxin than the Ca²⁺-sensitive rectification. A 4-aminopyridine-sensitive outward current (I _K,dr) with a threshold of around –30 mV and a second Ca²⁺-sensitive outward current (I _K,Ca) activated at around + 30 mV were observed from whole-cell voltage clamp recordings. I _K,Ca was blocked by tetraethylammonium and charybdotoxin. An 11-pS and a 122-pS channel, having characteristics similar to I _K,dr and I _K,Ca respectively, were identified from single-channel recordings. These observations showed how membrane depolarization of vascular smooth-muscle cells was regulated by these two populations of K⁺ channels under various conditions.     

血小板活化因子对豚鼠心室肌细胞钾电流及动作电位的影响

 目的：研究血小板活化因子(PAF)对豚鼠心室肌细胞钾电流及动作电位的影响。 方法:应用全细胞膜片钳技术，记录豚鼠心室肌细胞动作电位及钾电流(I_K 与I_K1)。 结果:当电极内液ATP浓度为5 mmol/L，1 μmol/L PAF使APD₉₀由对照的(225.8±23.3)ms延长至(352.8±29.8)ms(n=5, P<0.05)；使I_K尾电流在指令电压 +30 mV 时由对照的(173.5±16.7)pA降为(152.1±11.5)pA(P<0.05, n=4)；使I_K1在指令电压 -120 mV 时从(-6.1±1.3)nA降为(-5.6±1.1)nA(P<0.05, n=5)；当电极内液ATP 为0 mmol/L，APD₉₀明显缩短，1 μmol/L PAF使APD₉₀由对照的(153.0±24.6)ms缩短为(88.2±19.4)ms (n=5, P<0.01)，而用1 μmol/L格列本脲 ( I_KATP特异性阻滞剂)预处理后，恢复了PAF可显著延长动作电位时程的作用。 结论: PAF使缺血区K_ATP开放，动作电位时程缩短，却可抑制正常区I_K 与I_K1，使动作电位延长，从而放大了缺血区与正常区的不均一性，这可能与缺血时心律失常的发生有关。     

Arterial size determines the enhancement of contractile responses after suppression of endothelium-derived relaxing factor formation

We studied the effect of endothelium-derived relaxing factor (EDRF) on norepinephrine-induced contractile responses and on the tissue guanosine-3,5-phosphate (cGMP) concentration of isolated rabbit arteries with an increasing endothelium to smooth muscle cell ratio (aorta, femoral and mesenteric arteries). After suppression of EDRF formation (either by N ^G-nitro-l-arginine or, in mesenteric arteries, by saponin), contractions elicited by cumulative doses of norepinephrine were unaltered in aorta but were enhanced by 22.5% in femoral arteries and by 44.3% in mesenteric arteries (at the highest norepinephrine concentration). The cGMP concentration (pmol/mg protein) of unstimulated, endotheliumintact vessels decreased after suppression of EDRF formation from 1.09±0.24 to 0.74±0.28 in aortic, from 2.86±0.4 to 0.61±0.19 in femoral and from 6.3±0.9 to 0.7±0.15 in mesenteric arterial segments. The basal cGMP concentration did not differ in endothelium-denuded segments of these arteries, suggesting a similar basal activity of soluble guanylate cyclase (sGC). A higher sensitivity of sGC may have contributed to the higher cGMP concentration observed in the smaller arteries, since in the presence of sodium nitroprusside the cGMP concentration of endothelium-denuded segments increased 1.8-fold in aortic, 2.9-fold in femoral and 2.4 fold in mesenteric arterial segments. However, these differences in sGC activation cannot be solely responsible for the high basal cGMP concentration in endotheliumintact mesenteric arteries. The greater ratio of endothelium to smooth muscle cell layers in the smaller arteries might result in a higher EDRF concentration in the vascular wall and subsequently in a higher cGMP concentration. In conclusion, these data support the view of a greater importance of EDRF-mediated vascular control in small arteries than in large conduit arteries.     

Demonstration of endothelium-mediated increase in vascular smooth muscle cGMP,in a flexible coculture model

The purpose of this study was to test the feasibility of applying a novel coculture model for the investigation of endothelium-derived relaxing factor (EDRF) as well as exploring its applicability for investigating important cell-to-cell interactions. Bovine aortic endothelial cells (EC) were grown on micropore filters while porcine aortic smooth muscle cells (SMC) were grown separately on plates. When confluent these two cell layers were cocultured such that the EC maintained proper polarity and orientation to the underlying SMC. We found that coculturing EC with SMC for five minutes caused significant increase in SMC cGMP, 43±4 vs 268±13 fmols/well (p<0.0001). This EC-mediated effect was further augmented with EDRF agonists and with L-arginine supplementation, but was inhibited by nitro-L-arginine methyl ester (NAME) and reduced hemoglobin. When the EC were cocultured with subendothelial THP-1 monocytes for three hours prior to the SMC coculture, the EC mediated increase in SMC cGMP, both stimulated and unstimulated, was significantly reduced. We conclude that this flexible coculture model can be used to study EDRF release from EC and can be applied to study important cell-to-cell interactions that have been difficult to address in other models.     

Perivascular peptides relax cerebral arteries concomitant with stimulation of cyclic adenosine monophosphate accumulation or release of an endothelium-derived relaxing factor in the cat

Calcitonin gene-related peptide (CGRP), substance P (SP) and vasoactive intestinal polypeptide (VIP) have been proposed to be neurotransmitters/neuromodulators in cerebral perivascular nerve fibers. Here, we present pharmacological and biochemical evidence showing that these peptides have different modes of relaxing cerebral blood vessels in the cat. CGRP causes pronounced relaxation, this occurs simultaneously with stimulation of cyclic adenosine monophosphate (cAMP) accumulation. The strong VIP-induced dilatation is parallelled by cAMP accumulation, albeit of a lower magnitude than with CGRP. The SP-induced relaxation was much weaker than that of CGRP and VIP, and it was not associated with cAMP accumulation. Only at concentrations of SP where maximum relaxation had occurred, was a nonsignificant cAMP accumulation seen. The responses to SP and acetylcholine were absent in arteries where the endothelium had been removed, whereas the relaxations induced by CGRP and VIP persisted.     

Increased angiogenesis in chronic idiopathic myelofibrosis: vascular endothelial growth factor as a prominent angiogenic factor

Increased angiogenesis has been suggested to be implicated in the pathogenesis of chronic idiopathic myelofibrosis (CIMF). We hypothesized that vascular endothelial growth factor (VEGF) drives CIMF-associated angiogenesis, and thus, we aimed to determine its expression and biologic impact in newly diagnosed patients. All patients with CIMF diagnosed between 1990 and 2001, for whom adequate bone marrow specimens and clinical data were available, were deemed eligible. Each case was reclassified according to World Health Organization criteria. Microvessel density (MVD), as assessed by CD34 staining, and VEGF expression were examined by standard immunohistochemistry on paraffin-embedded trephine bone marrow biopsy specimens. The cytogenetic phenotype was determined by fluorescence in situ hybridization. Appropriate summary statistics were used for comparisons between groups; survival was calculated using Kaplan-Meier estimates. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model. Fifty-five patients with CIMF were investigated. With a median of 43 vascular lumina per 0.747 mm(2), patients with CIMF displayed significantly greater MVD than did age-matched controls (n = 10; median MVD, 19; P < .001) with equal distribution between the various fibrosis stages. Moreover, VEGF expression was significantly increased in CIMF (median, 12 cells/0.747 mm(2) versus 1.4 cells/0.747 mm(2); P = .01) and correlated with MVD (P = .001). However, neither MVD nor VEGF expression correlated with cytogenetics or clinical outcome. We conclude that in CIMF, increased MVD is detectable even in early (pre-)fibrotic stages. Moreover, we found significantly elevated VEGF expression correlating with MVD, thus suggesting VEGF to play a prominent angiogenic role and representing a novel potential therapeutic target in CIMF.     

一肾一夹和两肾一夹高血压和血压逆转大鼠血浆、心房和心室心钠素水平的变化特征

利用一肾一夹容量型和两肾一夹压力型大鼠肾血管性高血压所敛心肌肥厚及高血压逆转肥厚逆转模型,测定血浆、心房和心审心钠素水平。发现两型高血压大鼠血浆及左室的心钠素水平明显增高,左室及血浆心钠素浓度与相对室重呈正相关,左房心钠素浓度在一肾一夹型明显降低;随着高血压的逆转,两型大鼠血浆及心房心钠素水平基本恢复,增高了的心室心钠素由高水平下降。结果提示。在高血压、容量扩张并伴有心肌肥厚的病理情况下,心室心钠素可能起重要的代偿调节作用。