伊贝沙坦联合吲哒帕胺对原发性高血压的疗效及左室肥厚的逆转作用

目的观察伊贝沙坦与吲哒帕胺联用降压疗效及对原发性高血压（EH）左室肥厚（LVH）的逆转作用。方法将82例EH伴LVH患者随即分为A组（单用伊贝沙坦）40例，B组（伊贝沙坦与吲哒帕胺联用）42例。观察两组治疗前后及两组闯血压及LVH指标的变化。结果6个月后两组血压均较治疗前明显下降（P〈0．01），组闻降压幅度差异无显著性意义（P〉0．05），两组左室重量指数均较治疗前明显降低（P〈0．01），B组较A组更明显（P〈0．05）．结论伊贝沙坦联合吲哒帕胺能有效地控制血压且对EH的LVH有逆转作用。     

氯沙坦逆转高血压大鼠心肌重塑的实验研究

目的探讨氯沙坦对自发性高血压大鼠(SHR)心肌重塑的影响。方法16周龄雄性SHR20只,随机分为氯沙坦治疗组和SHR对照组。同龄雄性WKY鼠10只作为正常对照组。给予氯沙坦每天30mg/kg溶于饮水灌胃治疗17周。测定动脉收缩压、左心室壁的厚度、左心室重量与体重之比(LVW/BW)。透射电镜评估左心室肥厚(LVH)的程度。用真彩色图像分析系统计算左心室胶原容积分数。结果氯沙坦治疗组血压、LVW/BW、左室壁厚度与SHR对照组相比明显降低,但与WKY相比有所升高。透射电镜下氯沙坦治疗组心肌的超微结构与WKY相似,SHR的结构有异常改变。与SHR对照组相比,氯沙坦治疗组左心室胶原容积分数下降。结论氯沙坦能有效地降低SHR的血压、逆转高血压左室重塑。     

几种降压药对自发性高血压大鼠心血管肥厚的影响

目的：探讨相关的体液因素在高血压心血管肥厚发生中所起的作用。方法：用自发性高血压大鼠，分别以氨酰心安、巯甲丙脯氨酸及吲哒帕胺治疗。结果：所有经降压治疗的３组，血压均降到正常范围，但心脏、主动脉重量及各级动脉的变化各不相同。氨酰心安组：心脏及主动脉重量增加，主动脉，股动脉及肾脏微动脉中层厚度／管腔半径比值亦增加，与未经治疗的ＳＨＲ相似，唯程度较轻。巯甲丙脯氨酸组及吲哒帕胺组心脏、主动脉重量以及各级动脉的中层厚度／管腔半径比值均与正常血压的ＷＫＹ大鼠无明显差异。结论：β受体阻滞剂治疗虽使血压下降，但不能抑制心脏肥厚和动脉壁增厚。而血管紧张素转化酶抑制剂影响血管紧张素Ⅱ形成，在降压同时，可抑制心脏肥厚及动脉壁增厚的发生。Ｃａ２＋阻滞剂可收到同样的效果     

手术逆转压力负荷性左心室肥厚的实验研究

目的:探讨外科手术逆转压力负荷性左心室肥厚的有效性.方法:75只SD大鼠随机分为正常组(n=15)和肥厚组(n=60),后者行腹主动脉缩窄术造成左心室肥厚;肥厚组存活大鼠再随机分为实验组(n=26)和对照组(n=20),实验组大鼠再次手术解除腹主动脉的缩窄,术后每周取血液标本检测血管紧张素Ⅱ(angiotensinⅡ,...     

老年高血压患者血压变异性对左心室肥厚的影响

目的观察血压变异性(BPV)对老年性高血压患者左心室肥厚的影响 .方法老年性高血压患者100例,根据左室重量指数[LVMI]分为两组: 左室肥厚组和非左室肥厚组,进行24小时动态血压监测,以各时段(日间、夜间及24小时)血压的标准差作为血压变异性的量化指标.结果左室肥厚组日间、夜间及24小时收缩压BPV显著高于非左室肥厚组(p<0.01),日间、夜间及24小时收缩压 BPV与LVMI呈正相关,舒张压BPV与LVMI无相关性.结论收缩压B PV与高血压左室肥厚的发生和肥厚程度有关,老年性高血压患者更容易出现左室肥厚,在治疗老年性高血压时,要注意平稳降压.     

老年高血压患者血压变异性对左心室肥厚的影响

目的　观察血压变异性 (BPV)对老年性高血压患者左心室肥厚的影响 .方法　老年性高血压患者 10 0例 ,根据左室重量指数 [LVMI]分为两组 :左室肥厚组和非左室肥厚组 ,进行 2 4小时动态血压监测 ,以各时段 (日间、夜间及 2 4小时 )血压的标准差作为血压变异性的量化指标 .结果　左室肥厚组日间、夜间及 2 4小时收缩压BPV显著高于非左室肥厚组 (p <0 .0 1) ,日间、夜间及 2 4小时收缩压BPV与LVMI呈正相关 ,舒张压BPV与LVMI无相关性 .结论　收缩压BPV与高血压左室肥厚的发生和肥厚程度有关 ,老年性高血压患者更容易出现左室肥厚 ,在治疗老年性高血压时 ,要注意平稳降压     

16层螺旋CT对肌桥和壁冠状动脉的诊断价值

目的研究16层螺旋CT对肌桥的诊断及多时相重建对壁冠状动脉狭窄的评价。方法回顾总结我院自2005年9月～2008年3月期间,通过306例冠状动脉CT成像（冠脉CTA）的检查,检出了14例冠脉肌桥患者,经过原始轴位观察、多方位重组（MPR）、最大密度投影（MIP）对肌桥位置的确定,包埋的厚度、范围进行判定,并且利用多时相重建和4D技术对壁冠状动脉在收缩期和舒张期管腔狭窄程度进行评价。结果14例肌桥患者有10例发生在前降支中段,3例发生在对角支近段,其中8例壁冠状动脉在收缩期和舒张期均无狭窄,3例壁冠状动脉在收缩期有轻度狭窄,3例壁冠状动脉中度狭窄,近段冠脉有软硬斑块。结论16层螺旋CT能够很好的显示肌桥的位置、包埋的厚度和范围,对壁冠状动脉在不同时相管腔狭窄程度能够进行正确判断。     

维生素E增强雷米普利的抗高血压心肌肥厚作用及其可能机制

目的：探讨维生素Ｅ和雷米普利对大鼠高血压心肌肥厚的作用与机制。方法：建立腹主动脉缩窄性大鼠高血压心肌肥厚模型，采和低剂量ｒａｍｉｐｌａｔ，ＶｉｔＥ和一氧化氮合酶抑制剂Ｎ－Ｌ－ａｒｇｉｎｉｎｅ喂养大鼠，８周后观察大鼠血压，左室／体重比值，左室心肌组织超氧化物歧化酶活性和离体主动脉内皮依赖性舒张功能。     

氯沙坦（Losartan）逆转高血压大鼠血管壁超微结构的研究

目的 观察氯沙坦（Losartan）对自发性高血压大鼠（SHR）及正常对照组（WKY）的淋巴细胞胞浆游离钙[Ca^2 ]i、血管紧张素Ⅱ（AngⅡ）水平和血管壁超微结构的影响及其降压效应。方法 SHR28只分为3组，分别为3月龄对照组（SHRi）、6月龄对照组（SHR2）和Losartan治疗组（SHR3）。治疗组从3月龄开始予Losartan 20mg/kg/d治疗至6月龄。治疗前后检测鼠尾收缩压、淋巴细胞胞浆游离钙[Ca^2 ]i、血浆AngⅡ和肠系膜动脉超微结构。结果 Losartan对SHR有显著降压作用。治疗前SHR的淋巴细胞钙[Ca^2 ]i水平均显著性增加，随鼠龄增大而加大。肠系膜动脉出现明显血管壁损害，内皮细胞和平滑肌线粒体比表面均显著减少，而平滑肌细胞线粒体密度则显著增加。经Losartan治疗后，在降压的同时淋巴细胞[Ca^2 ]i显著性下降，血管壁超微结构的损害得到明显逆转。结论 高血压与血管平滑肌细胞存在的钙超负荷状态有关，并存在小动脉血管壁平滑肌和内皮细胞的超微结构损害。Losartan能有效逆转血管平滑肌的钙超负荷状态，降低SHR的动脉血压的同时逆转血管壁超微结构的损害。     

血管扩张素II-1型受体基因多态性与高血压及血浆NO、ET关系的研究

目的研究血管紧张素II-1型受体(AngiogenesisIIType1Receptor,AT1R)基因1166位点多态性与原发性高血压(EssentialHypertension,EH)的关系和血浆一氧化氮(NitricOxide,NO)、内皮素(Endothelin,ET)在EH发病中的相关性。方法采用聚合酶链反应、限制性内切酶酶解及电泳分型的方法对AT1R基因1166位点的多态性进行分析,硝酸还原酶法和放射免疫法分别测定两组血浆NO、ET值。结果①EH组中1166C等位基因频率显著高于对照组(P<0.05)。②EH组与对照组比较NO活性降低;ET水平升高(P<0.001)。③EH组中CC型血浆NO水平明显低于AC型(P<0.01);血浆NO、ET水平在AA、AC型之间无显著性差异(P<0.05)。结论①AT1R基因1166位点多态性与EH相关,1166C等位基因是EH发病的危险因素。②EH组存在血管内皮舒缩功能障碍,表现为血浆NO浓度降低、ET浓度升高。③EH血管内皮功能障碍与AT1R基因A1166C多态性有关,1166CC基因型可导致血管内皮舒缩功能障碍,提示EH血管内皮功能障碍可能存在遗传机制。④血浆NO水平与EH发病危险呈负相关;而血浆ET浓度升高是EH发病的危险因素。     

MAS受体与AT1受体的相互作用

RAS的2个重要成员Ang-(1-7)和血管紧张素II（Ang II）主要作用于MAS受体和AT1受体发挥作用。Ang-(1-7)和Ang II之间存在着复杂的相互作用，两者的受体在细胞和组织中相互作用，其可能的机制之一是受体的寡聚化     

Changes in Coronary Perfusion after Occlusion of Coronary Arteries in Kawasaki Disease

Purpose

Myocardial infarction in children with total occlusion of a coronary artery after Kawasaki disease is rare due to multiple collateral vessels. We aimed to investigate the changes in coronary perfusion associated with coronary artery occlusion after Kawasaki disease.

Materials and Methods

Eleven patients with coronary artery occlusion after Kawasaki disease were investigated. Serial coronary angiographies after total occlusion of a coronary artery were reviewed and the changes were described in all patients with additive information collected.

Results

The median age at the occlusion was 5.9 years old. The interval to occlusion was 6.2±6.9 years. Four left anterior descending coronary artery total occlusions and 10 right coronary artery total occlusions were detected. Immediate coronary artery bypass graft for left anterior descending coronary artery total occlusion made right coronary total occlusion occurred in all except one patient and the intervals thereof were 1 year, 1.8 years, and 4 years. Collaterals to the left coronary artery regressed after recanalization, while new collaterals to the right coronary artery developed. In three, collaterals to the right coronary artery decreased without recanalization without clinical signs.

Conclusion

The right coronary artery should be followed up carefully because of possible occlusion of new onset or changes in collaterals.     

急性冠脉短暂性缺血时心肌超微结构和球结膜微循环变化的实验研究

本文利用麦角新碱静脉注射建立家兔CAS模型,探讨了实验性动物CAS致急性短暂性心肌缺血与一过性外周微循环功能障碍、心电图异常、心肌超微结构病理变化相并行。说明心绞痛时心肌细胞水平有微循环障碍。     

Effects of Low Dose Pioglitazone on Restenosis and Coronary Atherosclerosis in Diabetic Patients Undergoing Drug Eluting Stent Implantation

Purpose

Thiazolidinediones are insulin-sensitizing agents that reduce neointimal proliferation and the adverse clinical outcomes associated with percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM). There is little data on whether or not low dose pioglitazone reduces adverse clinical outcomes.

Materials and Methods

The study population included 121 DM patients with coronary artery disease and they were randomly assigned to 60 patients taking 15 mg of pioglitazone daily in addition to their diabetic medications and 61 patients with placebo after the index procedure with drug-eluting stents (DESs). The primary end points were rate of in-stent restenosis (ISR) and change in atheroma volume and in-stent neointimal volume. The secondary end points were all-cause death, myocardial infarction (MI), stent thrombosis and re-PCI.

Results

There were no statistical differences in the clinical outcomes and the rate of ISR between the two groups [all-cause death; n=0 (0%) in the pioglitazone group vs. n=1 (1.6%) in the control group, p=0.504, MI; n=2 (3.3%) vs. n=1 (1.6%), p=0.465, re-PCI; n=6 (10.0%) vs. n=6 (9.8%), p=0.652, ISR; n=4 (9.3%) vs. n=4 (7.5%), p=1.000, respectively]. There were no differences in changes in neointimal volume, percent neointimal volume, total plaque volume and percent plaque volume between the two groups on intravascular ultrasonography (IVUS) study.

Conclusion

Our study demonstrated that low dose pioglitazone does not reduce rate of ISR, neointimal volume nor atheroma volume in DM patients who have undergone PCI with DESs, despite the limitations of the study.     

Losartan decreases vasopressin-mediated cAMP accumulation in the thick ascending limb of the loop of Henle in rats with congestive heart failure

Introduction: Vasopressin (AVP) stimulates sodium reabsorption and Na,K,2Cl‐cotransporter (NKCC2) protein level in the thick ascending limb (TAL) of Henle's loop in rats. Rats with congestive heart failure (CHF) have increased protein level of NKCC2, which can be normalized by angiotensin II receptor type‐1 (AT₁) blockade with losartan. Aim: In this study, we investigated whether CHF rats displayed changes in AVP stimulated cAMP formation in the TAL and examined the role of AT₁ receptor blockade on this system. Method: CHF was induced by ligation of the left anterior descending coronary artery (LAD). SHAM‐operated rats were used as controls. Half of the rats were treated with losartan (10 mg kg day^?1 i.p.). Results: CHF rats were characterized by increased left ventricular end diastolic pressure. Measurement of cAMP in isolated outer medullary TAL showed that both basal and AVP (10^?6 m ) stimulated cAMP levels were significantly increased in CHF rats (25.52 ± 4.49 pmol cAMP μg^?1 protein, P < 0.05) compared to Sham rats (8.13 ± 1.14 pmol cAMP μg^?1 protein), P < 0.05). Losartan significantly reduced the basal level of cAMP in CHF rats (CHF: 12.56 ± 1.93 fmol μg^?1 protein vs. Los‐CHF: 7.49 ± 1.08, P < 0.05), but not in Sham rats (SHAM: 4.66 ± 0.59 vs. Los‐SHAM: 4.75 ± 0.71). AVP‐mediated cAMP accumulation was absent in both groups treated with losartan (Los‐SHAM: 4.75 ± 0.71 and Los‐CHF: 7.49 ± 1.08). Conclusion: The results indicate that the increased NKCC2 protein level in the mTAL from CHF rats is associated with increased cAMP accumulation in this segment. Furthermore, the finding that AT₁ receptor blockade prevents AVP‐mediated cAMP accumulation in both SHAM and CHF rats suggests an interaction between angiotensin II and AVP in regulation of mTAL Na reabsorption.     

Agonistic AT1 Receptor Autoantibody Increases in Serum of Patients with Refractory Hypertension and Improves Ca^2＋ Mobilization in Cultured Rat Vascular Smooth Muscle Cells

Agonistic AT1 receptor autoantibodies （AT1-AAs） have been described in the patients with malignant hypertension or preeclampia. Furthermore, AT1-AAs were highly associated with refractory hypertension. Function of vascular smooth muscle cells （VSMCs） is important in the regulation of blood pressure. We investigated and compared the ability of angiotensin II （Ang II） and AT1-AAs to stimulate the intracellular calcium mobilization and cellular proliferation of rat VSMCs. Twenty-two patients with refractory hypertension, 24 patients with non-refractory hypertension and 37 normotensives were recruited. The serum of each patient was detected for the presence of AT1-AAs by ELISA. Ang II and the AT1-AAs from the sera of patients were used to stimulate rat VSMCs in vitro. AT1-AAs were detected in 10/22, 3/24 and 3/37 of patients with refractory hypertension, non-refractory hypertension and normotensives, respectively. AT1-AAs led the increase intracellular calcium mobilization in a dose-dependent manner and cellular proliferation of VSMCs just as Ang II. Both of these effects caused by AT1-AAs were blocked with losartan or a peptide corresponding to a part of the second extracellular loop of AT1 receptor. Since AT1-AAs exhibited pharmacological activity in rat VSMCs just as Ang II, they might play a role in the elevation of peripheral vascular resistance and in vascular remodeling. And AT1-AAs were suggested to involve in resistance to antihypertensive therapy.     

Losartan antagonism of angiotensin-II-induced potassium secretion across rat colon

 The effect of angiotensin II (ANG II) on potassium transport across the short-circuited rat distal colon was investigated using ⁸⁶Rb⁺ as a tracer for unidirectional K⁺ fluxes. The addition of high concentrations of ANG II (≥10^–6 M) to the serosal bathing solution had no effect on the mucosal to serosal flux of Rb⁺, but significantly increased the serosal to mucosal flux and abolished the basal net absorptive Rb⁺ flux. These ANG-II-induced alterations in Rb⁺ transport were blocked by the AT₁ receptor antagonist losartan and its metabolite EXP3174, which is also known to have AT₁ receptor antagonistic activity. In contrast, an AT₂ receptor antagonist, PD123319, did not prevent the alterations in colonic Rb⁺ transport induced by ANG II in vitro. At lower bath concentrations (10^–7 M to 10^–10 M ), ANG II had no measurable effects on Rb⁺ transport across this tissue but ANG II did have a bimodal effect on short-circuit current (I _sc), indicating additional effects on the electrogenic transport of other ions. Dose-dependent reductions in I _sc were observed between 10^–7 M (↓ΔI _sc=1.96±0.49 μEq·cm^–2·h^–1, n=6) and 10^–10 M (↓ΔI _sc=0.16±0.19 μEq·cm^–2·h^–1, n=7) ANG II, whereas I _sc was increased at the higher concentrations (↑ΔI _sc= 3.36±0.52 μEq·cm^–2·h^–1, n=7, at 10^–4 M). The ANG-II-induced increases and decreases in I _sc were both blocked by losartan but not by PD123319. These studies are the first to demonstrate an effect of ANG II on K⁺ transport across rat colon that is independent of aldosterone and mediated by AT₁ receptors. Received: 13 March 1998 Received after revision and accepted: 26 May 1998     

Regulation of glomerular angiotensin II receptor densities in renovascular hypertension: response to reduced sympathetic and vasopressin influence

The regulation of the density of angiotensin II receptors in renal glomeruli in response to changes in salt intake is altered in Sprague-Dawley rats with renovascular hypertension due to aortic constriction, and in hypertensive salt-sensitive Dahl rats (Sahlgren 1989, Sahlgren & Aperia 1989). This study examines the modulatory role of sympathetic activity and arginine-vasopressin on angiotensin II receptors in hypertensive Sprague-Dawley rats with aortic constriction as well as in normotensive control rats. Denervation of the left kidney caused a 50% increase in the glomerular angiotensin II receptor density in the denervated kidney in both hypertensive rats and normotensive controls. An even more marked increase in glomerular receptor density occurred in both hypertensive rats and controls after blocking the sympathetic nervous system with guanethidine. To block the effects of arginine-vasopressin we used a blocker of the V₁-receptors (predominant in vessels) and found an approximately 100% increase in the glomerular receptor density of angiotensin II in rats with aortic constriction. There was no reduction in blood pressure. Thus, on the receptor level the renin-angiotensin system is markedly influenced by the activity of other major pressor systems.