LOW DOSE INDAPAMIDE PLUS PERINDOPRIL COMBINATION EFFECTS ON CARDIOVASCULAR STRUCTURE AND FUNCTION IN GENETIC HYPERTENSION

1. Although the fixed combination preparations of thiazide and angiotensin-converting enzyme inhibitor are gaining wide acceptance in clinical practice, data on the basic pharmacology of the combinations are relatively limited. The long-term structural and functional effects of a fixed low dose (0.24 + 0.76 mg/kg per day) combination of indapamide + perindopril (I + P,S5590) is spontaneously hypertensive rats (SHR) were examined in the present study. 2. Male SHR (10-12 weeks) were treated with I + P or vehicle for 8 weeks. The blood pressure and heart rate were monitored by weekly measurements. At the end of the treatment period, left ventricular, aortic and intramyocardial coronary arteriole structures were assessed. Contractile and relaxant properties of mesenteric arteries were determined by wire-myography. 3. Indapamide + perindopril combination caused a significant lowering of both systolic (P < 0.001) and diastolic (P < 0.001) blood pressures. Left ventricle plus septum:bodyweight ratio (P < 0.001), aortic medial cross-sectional area (P < 0.05) and media:lumen ratios (P < 0.005) were all significantly reduced by I + P treatment. In contrast, the effect of I + P on intramyocardial coronary vascular structure did not reach statistical significance. There was some improvement in endothelium-independent vasorelaxation of mesenteric vessels but contractile responses to noradrenaline and calcium were unaffected by treatment. 4. In summary, a low dose I + P combination treatment of SHR partly normalizes both systolic and diastolic blood pressures. Cardiac and larger vessel hypertrophy was reversed but intramyocardial coronary arteriole structure was not as readily regressed by the end of the study.     

大鼠心肌梗死后血管新生及VEGF表达的形态学观察

[目的]探讨大鼠心肌梗死后血管新生及其意义。[方法]采用SD大鼠冠状动脉前降支结扎形成心肌梗死模型,应用免疫组织化学方法于术后1、2、3、7、15、30、90d的大鼠心肌进行VWF、α-SMA及VEGF标记,并进行微血管、小动脉及VEGF阳性细胞记数。[结果]微血管密度和小动脉密度于术后2d开始增加,3～7d达到高峰,VEGF于术后2～7d呈高表达。[结论]心肌梗死后,血管的新生有明显的时段性,提示心肌梗死后在早期采用促进血管新生的措施可能比较合适。     

Reactivity of Brain Parenchymal Arterioles after Ischemia and Reperfusion

Objective: We investigated the effect of ischemia and reperfusion on the vasoactive function of penetrating brain parenchymal arterioles under pressurized conditions. Methods: Parenchymal arterioles (<50 μm in diameter) from within the middle cerebral artery territory were dissected from male Wistar rats that were either nonischemic control (n = 16) or ischemic for one hour and reperfused for 24 hours (n = 16) by temporary filament occlusion of the middle cerebral artery. Arterioles were mounted on glass cannulas within an arteriograph chamber that allowed for the measurement of lumen diameter and control over intravascular pressure. Results: After one hour of equilibration at 10 mmHg, spontaneous myogenic tone developed in both groups of animals, constricting control arterioles from 69 ± 9 to 49 ± 11 μm (29.5 ± 10.2%) and ischemic arterioles from 66 ± 9 to 45 ± 11 μm (33.1 ± 14.1%); p > 0.05. Contraction to the nitric oxide synthase inhibitor nitro‐L‐arginine (10^–4M) was significantly diminished in ischemic arterioles, constricting only 3.2 ± 3.3 vs. 15.6 ± 12.5% in control arterioles (p = 0.017). Both groups dilated to nifedipine; however, the response was significantly diminished after ischemia. The EC₅₀ for nifedipine in control arterioles was 3.54 ± 0.11 vs. 9.90 ± 0.71 nM for ischemic arterioles (p = 0.024). Conclusions: These findings demonstrate that functional changes occur in brain parenchymal arterioles after ischemia and reperfusion, a result that may significantly influence stroke outcome by altering blood flow to an ischemic region.     

Mechanisms of enhanced basal tone of brain parenchymal arterioles during early postischemic reperfusion: role of ET-1-induced peroxynitrite generation

The contributions of vasoconstrictors (endothelin-1 (ET-1), peroxynitrite) and endothelium-dependent vasodilatory mechanisms to basal tone were investigated in parenchymal arterioles (PAs) after early postischemic reperfusion. Transient middle cerebral artery occlusion (tMCAO) was induced for 2 hours with 30 minutes reperfusion in male Wistar rats and compared with ischemia alone (permanent MCAO (pMCAO); 2.5 hours) or sham controls. Changes in lumen diameter of isolated and pressurized PAs were compared. Quantitative PCR was used to measure endothelin type B (ET_B) receptors. Constriction to intravascular pressure (‘basal tone'') was not affected by tMCAO or pMCAO. However, constriction to inhibitors of endothelial cell, small- (SK) and intermediate- (IK) conductance, Ca²⁺-sensitive K⁺ channels (apamin and TRAM-34, respectively) were significantly enhanced in PAs from tMCAO compared with pMCAO or sham. Addition of the ET_B agonist sarafotoxin caused constriction in PAs from tMCAO but not from sham animals (21±4% versus 3±3% at 1 nmol/L; P<0.01) that was inhibited by the peroxynitrite scavenger FeTMPyP (5,10,15,20-tetrakis (N-methyl-4′-pyridyl) porphinato iron (III) chloride) (100 μmol/L). Expression of ET_B receptors was not found on PA smooth muscle, suggesting that constriction to sarafotoxin after tMCAO was due to peroxynitrite and not ET_B receptor expression. The maintenance of basal tone in PAs after tMCAO may restrict flow to the ischemic region and contribute to infarct expansion.     

肾复康Ⅱ号胶囊对IgA肾病大鼠血清醛固酮及肾内小动脉病变的影响

目的:观察肾复康Ⅱ号胶囊对IgA肾病(IgAN)肾内小动脉病变大鼠醛固酮诱导的血管内皮细胞生长因子(VEGF)、增殖细胞核抗原(PCNA)、人基质金属蛋白酶-9(MMP-9)的表达,探讨肾复康Ⅱ号胶囊对IgAN小动脉病变的防治机制.方法:将70只健康雄性SD大鼠分为空白组、模型组、治疗组(肾复康组)、中药对照组(黄葵组...     

骨间后血管及其返支为蒂串连皮瓣的临床应用

目的为手部皮肤软组织缺损探寻一种新的修复方法.方法在40侧人体上肢标本上,对骨间后血管及其返支的来源、走行、分支、分布及吻合情况进行解剖观察的基础上,设计以前臂骨间后血管及其返支为蒂的串连皮瓣.1998年8月～2000年7月间临床应用此皮瓣逆行移位修复手背远侧及手指背侧皮肤缺损17例.皮瓣范围最大15cm×10cm,最小7cm×5cm.结果术后随访3周～6个月,除1例皮瓣远端有2cm×3cm坏死外,其余皮瓣全部成活,外观及功能满意.结论此皮瓣不损伤肢体主要血管,血管蒂较长,皮瓣切取面积较宽,厚薄适中,可用于修复拇指、手背至手指近节背侧的皮肤软组织缺损.手术简便,效果良好.     

食管壁微动脉及毛细血管的观测

目的;观察食管壁内动脉血供及微血管构筑的基础性研究资料。方法：随机选取新鲜胎尸25具,墨汁灌注,组织切片;家兔5只,钙钴法碱性磷酸酶染色。光学显微镜下观测。结果;食管壁内各层均存在动脉网,粘膜下层动脉网丰富,分深浅两层;各层毛细血管特点各异,外膜层稀,肌层有肌束间血管网,粘膜下层呈丛状,粘膜层最丰富;食管各段毛细血管密度差异不大,但颈段前壁纵形肌、胸上段后壁粘膜层有相对毛细血管贫乏区。结论：食管的各段各层均存在动脉网,毛细血管密度差异不大,能有限代偿食管壁外供血动脉的阻断。     

Diabetes-induced activation of protein kinase C inhibits store-operated Ca<Superscript>2+</Superscript> uptake in rat retinal microvascular smooth muscle

Aims/Hypothesis To assess the effects of diabetes-induced activation of protein kinase C (PKC) on voltage-dependent and voltage-independent Ca²⁺ influx pathways in retinal microvascular smooth muscle cells.Methods Cytosolic Ca²⁺ was estimated in freshly isolated rat retinal arterioles from streptozotocin-induced diabetic and non-diabetic rats using fura-2 microfluorimetry. Voltage-dependent Ca²⁺ influx was tested by measuring rises in [Ca²⁺]_i with KCl (100 mmol/l) and store-operated Ca²⁺ influx was assessed by depleting [Ca²⁺]_i stores with Ca²⁺ free medium containing 5 µmol/l cyclopiazonic acid over 10 min and subsequently measuring the rate of rise in Ca²⁺ on adding 2 mmol/l or 10 mmol/l Ca²⁺solution.Results Ca²⁺ entry through voltage-dependent L-type Ca²⁺ channels was unaffected by diabetes. In contrast, store-operated Ca²⁺ influx was attenuated. In microvessels from non-diabetic rats 20 mmol/l D-mannitol had no effect on store-operated Ca²⁺ influx. Diabetic rats injected daily with insulin had store-operated Ca²⁺ influx rates similar to non-diabetic control rats. The reduced Ca²⁺ entry in diabetic microvessels was reversed by 2-h exposure to 100 nmol/l staurosporine, a non-specific PKC antagonist and was mimicked in microvessels from non-diabetic rats by 10-min exposure to the PKC activator phorbol myristate acetate (100 nmol/l). The specific PKC antagonist LY379196 (100 nmol/l) also reversed the poor Ca²⁺ influx although its action was less efficacious than staurosporine.Conclusion/interpretation These results show that store-operated Ca²⁺ influx is inhibited in retinal arterioles from rats having sustained increased blood glucose and that PKC seems to play a role in mediating this effect.Abbreviations DAG Diacylglycerol - PKC protein kinase C - [Ca²⁺]_i intracellular calcium concentration - STZ streptozotocin - SPP staurosporine - SR sarcoplasmic reticulum - MVSM microvascular smooth muscle - CPA cyclopiazonic acid - PMA phorbol myristate acetate - VDCC voltage-dependent Ca²⁺ channels     

老年原发性高血压左心室肥厚患者心肾微动脉的病理特征

目的 研究老年原发性高血压左心室肥厚(LVH)患者心、肾微动脉改变的病理特点,以发现两个靶器官微动脉结构变化的异同和相互联系.方法 从解放军总医院1954-2004年连续尸检的病例中,选取年龄≥60岁经临床和尸检证实为原发性高血压LVH患者25例和对照组8例的心、肾标本为研究对象,其中原发性高血压组再按LVH程度(Ⅰ～Ⅲ级)分为三组,予HE、Masson染色后,用光镜配合电脑图像分析,定量检测心、肾微动脉几何形态学参数,并用半定量的方法 评估微动脉的损伤指数和血浆蛋白浸润指数.结果 高血压组心、肾微动脉血管几何形态学参数随LVH程度的增加呈现出有规律的变化趋势,表现为血管内径(ID)、管腔横截面积(LCSA)减小,而血管壁厚度(WT)、血管壁横截面积(WCSA)、壁腔横截面积比值(WCSA/LCSA)和壁厚内径比值(WT/ID)增大;不同外径(OD)范围的心肌、肾脏微动脉WCSA/LCSA和WT/ID比较均发现,随OD的增加,血管的WCSA/LCSA和WT/ID比值减小;相同OD范围的心、肾微动脉各项血管几何形态学参数比较有明显差异(P＜0.05);高血压组心、肾微动脉血浆蛋白浸润指数、血管损伤指数高于对照组(P＜0.01);各组肾脏微动脉血管损伤指数、血浆蛋白浸润指数均高于心肌微动脉(P＜0.01).结论 原发性高血压患者心、肾微动脉均出现向心性重构,在血管OD范围为10～50 μm的微动脉表现最明显,OD＜50μm的微动脉最易出现闭塞;心、肾微动脉血管重构随高血压LVH程度的增加而加重;高血压肾脏微动脉损伤比心肌微动脉重.微动脉病变是高血压靶器官损害的重要病理学基础.