实验性高血压大鼠大脑中动脉超微结构改变及其药物影响

目的　探讨高血压大鼠大脑中动脉超微结构的变化及血管紧张素转换酶抑制剂的影响。方法　选用易卒中型肾血管性高血压大鼠模型 ,分为高血压组、卡托普利治疗组 ,并与假手术正常血压大鼠作对照 ,分别于肾动脉狭窄术后 4、8和 12周处死动物 ,取大脑中动脉 ,制片后分别用光镜和透射电镜观察 ,并进行体视学定量分析。结果　术后 4周时高血压组大脑中动脉光镜下无明显形态学变化 ;8周和 12周时中膜厚度、中膜与管腔比值与假手术对照组相比均有显著性差异 (P <0 .0 5 ) ;卡托普利治疗后中膜厚度、壁腔比值均小于高血压组 ,差异有显著性 (P <0 0 5 )。术后 4周高血压组大脑中动脉超微结构仅轻度异常 ;术后 8周细胞间隙增宽 ,间质明显水肿 ;12周时平滑肌细胞坏死 ,内质网扩张 ,线粒体部分空泡变性 ,核自溶 ,间质增生 ;卡托普利组各时期超微结构改变不明显。结论　高血压可致大脑中动脉肥厚和超微结构破坏 ,而卡托普利可以减轻高血压所致的大脑中动脉结构破坏。     

实验性高血压大鼠大脑中动脉超微结构改变及其药物影响

目的探讨高血压大鼠大脑中动脉超微结构的变化及血管紧张素转换酶抑制剂的影响.方法选用易卒中型肾血管性高血压大鼠模型,分为高血压组、卡托普利治疗组,并与假手术正常血压大鼠作对照,分别于肾动脉狭窄术后4、8和12周处死动物,取大脑中动脉,制片后分别用光镜和透射电镜观察,并进行体视学定量分析.结果术后4周时高血压组大脑中动脉光镜下无明显形态学变化;8周和12周时中膜厚度、中膜与管腔比值与假手术对照组相比均有显著性差异(P<0.05);卡托普利治疗后中膜厚度、壁腔比值均小于高血压组,差异有显著性(P<0.05).术后4周高血压组大脑中动脉超微结构仅轻度异常;术后8周细胞间隙增宽,间质明显水肿;12周时平滑肌细胞坏死,内质网扩张,线粒体部分空泡变性,核自溶,间质增生;卡托普利组各时期超微结构改变不明显.结论高血压可致大脑中动脉肥厚和超微结构破坏,而卡托普利可以减轻高血压所致的大脑中动脉结构破坏.     

缬沙坦对卒中易感型自发性高血压大鼠脑血管结构的影响

目的 :研究长期口服血管紧张素Ⅱ 1型受体拮抗剂———缬沙坦对卒中易感型自发性高血压大鼠(SHRsp)脑血管形态结构的影响 ,探讨其可能的脑保护机制。 方法 :6周龄雄性SHRsp2 6只随机分为 3组 ,以 8只 6周龄雄性正常血压大鼠 (WKY)作为正常对照 ,记录血压和脑卒中临床表现评分 ,18周后断头处死 ,镜下观察脑血管结构。结果 :① 18周后SHRsp组和小剂量缬沙坦 (2 0mg·kg-1·d-1)用药组 (SHRSP加V2 0 组 )血压均分别高于WKY组和大剂量缬沙坦 (4 0mg·kg-1·d-1)用药组 (SHRSP加V40 组 ) ,P <0 .0 5。②SHRsp组脑卒中临床表现评分明显高于SHRSP加V2 0 组和SHRSP加V40 组 ,SHRSP组死亡率为 33.33% ,SHRSP加V2 0 组和SHRSP加V40 组均无死亡。③SHRsp组脑动脉中膜厚度 /管腔半径的比值明显高于WKY组、SHRSP加V2 0 组和SHRSP加V40 组 ,P<0 .0 5 ;而后三者之间脑动脉中膜厚度 /管腔半径的比值差异均无显著性意义 (P >0 .0 5 )。结论 :缬沙坦可通过降低SHRsp脑动脉中膜厚度 /管腔半径的比值、干预血管重构发挥脑血管保护作用 ,此作用与血压无关。     

高血压大鼠脑血管功能损害的临界关闭压评价

目的通过临界关闭压(CCP)动态观察高血压脑微动脉平滑肌的收缩程度与形态改变间的关系。方法对照组和高血压组大鼠各80只,在高血压形成术后的不同时间点,分别测定脑血管CCP、脑血流自动调节下限(LLCA)和脑血管形态变化。结果高血压组大鼠的CCP逐渐升高,到14、16周明显高于对照组(P<0.05)。CCP的升高与平均动脉压、微动脉中膜厚度及LLCA呈正相关(P<0.05),并且在血压升高初期和血压较高后变化明显,呈倒“S”形改变(P<0.05)。结论高血压大鼠脑微动脉平滑肌的收缩程度明显增强,是微动脉中膜增厚的功能表现,并且在血压升高初期和血压较高后改变比较明显。     

螺内酯对继发性高血压大鼠肾脏的保护作用

目的观察螺内酯对高血压大鼠肾动脉重构的影响。方法在48只雄性Wistar大鼠中，随机选出36只，以腹主动脉缩窄法制备高血压模型，再随机分为3个亚组：高血压模型组（模型组，自来水灌胃＋饮用1％盐水），高血压培哚普利组[培哚普利组，培哚普利2mg／（kg&#183;d）灌胃＋饮用1％盐水]，高血压螺内酯组[螺内酯组，螺内酯20mg／（kg&#183;d）灌胃＋饮用1％盐水]；其余12只进入假手术对照组（假手术组，只分离腹主动脉但不结扎，自来水灌胃＋饮用自来水）。8周后超声检测肾动脉及肾内动脉收缩期和舒张期阻力指数（RI）和血流速度并比较各组的差异；12周后颈动脉插管法测量血压及病理学方法测定肾内动脉的血管重构指标。结果培哚普利和螺内酯均能降低高血压大鼠收缩压及舒张压（P〈0．01），均使高血压大鼠的肾动脉RI、肾内动脉RI、血管内膜中膜厚度与管腔内腔的比值（M／L）及肾动脉内中膜纤维化程度明显下降（P〈0．01～0．05），螺内酯上述作用比培哚普利更明显，螺内酯还能使高血压大鼠内中膜厚度显著降低（P〈0．01）；虽然培哚普利和螺内酯均能使高血压大鼠肾动脉及肾内动脉舒张末期血流速度及肾内动脉面积增加（P〈0．01～0．05），螺内酯能更进一步降低肾动脉RI、M／L和内中膜纤维化比率（P〈0．01～0．05）。结论培哚普利和螺内酯均能降低高血压大鼠血压，改善动脉重塑，在改善动脉重塑方面螺内酯效果比培哚普利更明显。     

易卒中型肾血管性高血压大鼠脑大动脉重塑类型

目的观察易卒中型肾血管性高血压大鼠脑动脉的结构变化。方法将易卒中型肾血管性高血压大鼠第4周和8周时处死,脑大动脉切片用HE染色后,测量这些大动脉重塑参数,对免疫组织化学对纤维连接素蛋白表达进行图象分析。结果易卒中型肾血管性高血压大鼠组血压高于对照组。易卒中型肾血管性高血压大鼠第4周时颈总动脉平滑肌细胞总数(282.5±59.6个)和纤维连接素蛋白表达量(184.3±2.4)较对照组(344.7±50.9个和181.4±3.2)减少,单个细胞面积增加;第8周时,管壁厚度(74.8±12.3μm)、横截面积(233428.3±76487.9μm2)、壁腔比(0.086±0.007)、壁面积比(0.00030±0.00011)、单个细胞面积(547.9±111.8μm2)和纤维连接素蛋白表达量(180.8±2.3)均增加,单位面积细胞数(282.5±59.6个)减少。易卒中型肾血管性高血压大鼠基底动脉横截面积第4周和第8周时(15867.4±1316.9μm2和22556.5±6485.6μm2)均高于对照组(13598.9±1090.8μm2),纤维连接素蛋白表达量第8周时(166.2±5.1)增加。第4周时易卒中型肾血管性高血压大鼠大脑中动脉管腔内直径(208.6±59.6μm)增加,壁腔比(0.094±0.048)和壁面积比(0.00150±0.00040)减少;第8周时管壁厚度(23.3±7.2μm2)、横截面积(16236.2±6538.4μm2)和平滑肌细胞总数(52.2±16.1个)增加,管腔内直径和壁面积比与对照组的差异仍有统计学意义。结论易卒中型肾血管性高血压大鼠不同脑动脉在高血压不同时期的重塑类型和机制     

高血压进展期动脉肿瘤坏死因子—α的表达及构型重塑的研究

方法 用原位杂交、免疫组织化学和透射电镜方法,对24周龄自发性高血压大鼠（SHR）肠系膜动脉肿瘤坏死因子－α（TNF－α）表达及动脉壁构型重塑情况进行了研究。结果 显示,SHR肠系膜动脉壁内皮细胞,平滑肌细胞,外膜细胞TNFα浓度明显高于正常血压大鼠（P＜0．01）;而且小动脉内弹性膜崩解,内膜增厚,中膜平滑肌细胞（SMC）肥大变形,细胞外基质增多,许多SMC内出现空泡改变,少数细胞出现溶解坏死。结论 高血压时,动脉壁细胞TNF－α表达水平增高与动脉壁构型重塑有明显关系。TNF在高血压进展期动脉硬化性病变中可能起着重要作用。     

螺内酯对继发性高血压大鼠肾脏的保护作用

目的 观察螺内酯对高血压大鼠肾动脉重构的影响.方法 在48只雄性Wistar大鼠中,随机选出36只,以腹主动脉缩窄法制备高血压模型,再随机分为3个亚组:高血压模型组(模型组,自来水灌胃 饮用1%盐水),高血压培哚普利组[培哚普利组,培哚普利2 mg/(kg·d)灌胃 饮用1%盐水],高血压螺内酯组[螺内酯组,螺内酯20 mg/(kg·d)灌胃 饮用1%盐水];其余12只进入假手术对照组(假手术组,只分离腹主动脉但不结扎,自来水灌胃 饮用自来水).8周后超声检测肾动脉及肾内动脉收缩期和舒张期阻力指数(RI)和血流速度并比较各组的差异;12周后颈动脉插管法测量血压及病理学方法测定肾内动脉的血管重构指标.结果 培哚普利和螺内酯均能降低高血压大鼠收缩压及舒张压(P＜0.01),均使高血压大鼠的肾动脉RI、肾内动脉RI、血管内膜中膜厚度与管腔内腔的比值(M/L)及肾动脉内中膜纤维化程度明显下降(P＜0.01～0.05),螺内酯上述作用比培哚普利更明显,螺内酯还能使高血压大鼠内中膜厚度显著降低(P＜0.01);虽然培哚普利和螺内酯均能使高血压大鼠肾动脉及肾内动脉舒张末期血流速度及肾内动脉面积增加(P＜0.01～0.05),螺内酯能更进一步降低肾动脉RI、M/L和内中膜纤维化比率(P＜0.01～0.05).结论 培哚普利和螺内酯均能降低高血压大鼠血压,改善动脉重塑,在改善动脉重塑方面螺内酯效果比培哚普利更明显.     

有氧运动抑制高血压大鼠肠系膜动脉CaCCs通道蛋白TMEM16A表达上调

目的探究有氧运动对高血压大鼠肠系膜动脉血管钙激活氯离子通道(Ca CCs)蛋白TMEM16A的表达及血管张力的影响。方法正常血压大鼠(WKY)随机分为正常运动组(WKY-EX)和正常安静组(WKY-SED);自发性高血压大鼠(SHR)随机分为高血压运动组(SHR-EX)和高血压安静组(SHR-SED)。运动组进行12周跑台运动(20 m/min,60 min/d,5 d/w,12 w)。12周有氧运动后,取各组大鼠的肠系膜动脉(3级)进行形态学观察、离体微血管张力测定及蛋白免疫印迹分析TMEM16A蛋白。结果高血压安静组大鼠心率(HR)和收缩压(SBP)水平较正常安静组显著增加(P0. 05),而12周有氧运动可显著降低SHR大鼠的体质量(BW)、HR、SBP水平(P0. 05)。高血压安静组大鼠肠系膜动脉血管平滑肌层厚度较正常安静组明显增加,而12周有氧运动可下调SHR大鼠的肠系膜动脉血管平滑肌层厚度。高血压安静组大鼠肠系膜动脉对去甲肾上腺素(NE)诱导的张力反应较正常安静组显著增加(P0. 05),而12周有氧运动可显著降低SHR大鼠肠系膜动脉对NE诱导的张力反应。高血压安静组大鼠肠系膜动脉对特异性Ca CCs蛋白阻断剂(T16Ainh-A01)的敏感性较正常安静组显著增加(P0. 05),而12周有氧运动可显著降低SHR大鼠肠系膜动脉对此药物的敏感性(P0. 05)。高血压安静组大鼠肠系膜动脉中Ca CCs通道蛋白TMEM16A的表达水平较正常安静组显著增加(P0. 05),而12周有氧运动可显著降低SHR大鼠肠系膜动脉中Ca CCs通道蛋白TMEM16A的表达水平(P0. 05)。结论有氧运动可有效下调SHR大鼠血压,下调Ca CCs通道蛋白TMEM16A表达,抑制高血压诱导的Ca CCs通道的病理性代偿,从而引起血管功能的改善。     

高血压进展期动脉肿瘤坏死因子-α的表达及构型重塑的研究

方法　用原位杂交、免疫组织化学和透射电镜方法，对24周龄自发性高血压大鼠（SHR)肠系膜动脉肿瘤坏死因子-α(TNF-α)表达及动脉壁构型重塑情况进行了研究。结果显示，SHR肠系膜动脉壁内皮细胞，平滑肌细胞，外膜细胞TNFα浓度明显高于正常血压大鼠(P<0.01)；而且小动脉内弹性膜崩解，内膜增厚，中膜平滑肌细胞(SMC)肥大变形，细胞外基质增多，许多SMC内出现空泡改变，少数细胞出现溶解坏死。结论　高血压时，动脉壁细胞TNF-α表达水平增高与动脉壁构型重塑有明显关系。TNF在高血压进展期动脉硬化性病变中可能起着重要作用。     

Morphometric study of structural changes in the mesenteric blood vessels of spontaneously hypertensive rats

Structural changes of three categories of mesenteric arteries (representing elastic, muscular and arteriolar vessels) from 10- to 12-week-old and 28-week-old spontaneously hypertensive rats (SHR) were studied morphometrically at the light microscope level, and the results compared with age-matched Wistar-Kyoto normotensive rats. In 10- to 12-week-old SHR, hypertrophy of the vessel wall occurred only in the muscular and arteriolar vessels. At 28 weeks, further thickening of the vessel wall occurred in the muscular and arteriolar vessels, and the superior mesenteric artery (elastic vessel) was also thickened in the SHR. There was no evidence that the wall of the relaxed hypertrophied vessels encroached upon the lumen of the vessel. The structural basis for the increase in the vessel wall thickness varied with vessel type. In the superior mesenteric artery, increase in the media at 28 weeks of age would be consistent with hypertrophy of the smooth muscle cells. In the large muscular arteries, at 10-12 weeks of age, increase in medial mass occurred with increase in the number of the smooth muscle cell layers whereas at 28 weeks further increase in media could be due to hypertrophy of the smooth muscle cells. In the small arteriolar vessels, medial enlargement was due at all ages to an increase in the number of smooth muscle layers. Our results show that in the SHR hypertrophy of the media occurs not only in the small arteriolar vessels, but also in large elastic and muscular arteries.     

实验性高血压所致的颅内大动脉损害

为观察实验性高血压所致的颅内大动脉损害的特征．将易卒中型肾血管性高血压大鼠的大脑中动脉和基底动脉进行形态学测量．并观察了用卡托普利抗高血压治疗后这些测量参数的变化。结果发现，高血压大鼠的大脑中动脉和基底动脉均有中层肥厚，但前者主要由平滑肌细胞增殖、肥大引起，后者却主要是血管壁重构的结果。卡托普利抗高血压治疗可控制平滑肌细胞增殖、肥大，但不能改善血管壁重构。以上结果提示，高血压所致的颅内动脉损害主要表现为血管中层肥厚，而且不同血管对高血压和抗高血压治疗的反应有差异。     

Morphometric study of mesenteric arteries from genetically hypertensive Dahl strain rats

Morphometric measurements on different arteries at the light-microscopic level and ultrastructural studies of the mesenteric arteries were carried out in salt-sensitive (DS) and salt-resistant (DR) Dahl rats given a high-salt (8%) or low-salt (0.4%) diet for 6-7 weeks. Hypertension was produced in DS rats given high-salt diet (DS-H), while only moderate hypertension was produced in DS rats given low-salt diet (DS-L). Blood pressure in DR rats given high salt (DR-H) and low salt (DR-L), however, was normal. Cross-sectional area of the media was increased significantly in the superior mesenteric artery (an elastic artery), large mesenteric arteries (muscular arteries) and small mesenteric arteries (small muscular arteries or arterioles) from DS-H rats. In all the vessel types, this increase was positively correlated with the increase in blood pressure. In the superior mesenteric artery, medial wall increase was probably due to an increase in intercellular space, and/or hypertrophy of the smooth muscle cells. Similarly, increase in the media of small mesenteric arteries was probably due to hypertrophy of the smooth muscle cells. In contrast, increase in the media of large mesenteric arteries was related to hyperplasia of the smooth muscle cells. Damage to endothelial cells was noted in the 3 vessel types from DS-H. Intimal lesions composed of myointimal cells were found in the superior mesenteric arteries of all the rat groups. Our results showed that the incidence of these lesion formations was higher in the following order: DS-H greater than DS-L greater than DR-H greater than DR-L, suggesting that the degree of hypertension (DS vs. DR rats) and the amount of salt in the diet (DR-H vs. DR-L) may be some of the factors contributing to the development of these lesions. We conclude that hyperreactivity of the arteries due to increase in medial smooth muscle mass (e.g. muscular arteries), and/or probably impaired relaxation capability of the arteries in the DS-H rats due to endothelial cell damage, may contribute to the elevation of BP in the Dahl model of genetic hypertension.     

Cardiovascular hypertrophy in one-kidney, one-clip renal hypertension is resistant to heparin

OBJECTIVE: Heparin inhibits vascular hypertrophy in angiotensin-induced hypertension, in addition to its well-known role in inhibiting injury-induced vascular smooth muscle proliferation. We tested whether hypertension and vascular hypertrophy could be reduced by heparin independently from the renin-angiotensin system. METHODS: Rats were made hypertensive with a one-kidney, one-clip (1K1C) procedure and received heparin from osmotic minipumps (0.3 mg/h per kg i.v.) or saline vehicle for 2 weeks. Blood pressure was measured by the tail-cuff method and vessel cross-sectional area was measured by morphometry in the aorta and mesenteric arteries. Proliferation was assessed with bromodeoxyuridine labelling. RESULTS: Blood pressure elevation and cardiovascular hypertrophy were evident in 1K1C rats. The media of mesenteric arteries was increased by 25%, and the media : lumen ratio by 35%, in hypertensive rats. DNA synthesis by smooth muscle cells in the mesenteric arteries was increased sevenfold in renal hypertension. Heparin treatment did not influence either the increase in blood pressure, the cardiovascular hypertrophy response or hypertension-mediated proliferation of arterial smooth muscle cells. CONCLUSIONS: These data suggest that the vascular hypertrophy mechanisms operating in 1K1C renal hypertension are not inhibited by heparin and thus are different from those in angiotensin-mediated hypertension. Identifying such mechanisms in the future will be important for devising appropriate intervention strategies in angiotensin-independent forms of vascular hypertrophy.     

Involvement of Ras-regulated myosin light chain phosphorylation in the captopril effects in spontaneously hypertensive rats

BACKGROUND: Early treatment with captopril prevents the development of hypertension by inhibiting the generation of angiotensin II and smooth muscle contraction. Although smooth muscle contraction is regulated by myosin light chain phosphorylation (MLC-P), the role of MLC-P in captopril effects in hypertension has not been described. Therefore, we treated spontaneously hypertensive rats (SHR) with captopril and investigated the effects of this agent on downstream signaling. METHODS: Male SHR (n = 12) were treated with captopril (3.7 mmol/L in drinking water) beginning in utero and continuing up to 12 weeks of age. Age- and sex-matched untreated SHR and Wistar-Kyoto (WKY) rats were used as controls. Rats were split into three subgroups and were sacrificed at 12, 18, or 24 weeks of age. Systolic blood pressure, left ventricular weight, and body weight were measured. Mesenteric arteries were removed for histologic and biochemical studies. RESULTS: At 12 weeks, captopril significantly decreased systolic blood pressure (from 198 +/- 10 to 125+/-16 mm Hg), reduced left ventricular weight-to-body weight ratios (from 2.94 +/- 0.06 to 2.17 +/- 0.08 mg/g), and prevented vascular remodeling in mesenteric arteries in SHR. Ras expression, extracellular receptor kinase phosphorylation (ERK-P), myosin light chain kinase (MLCK) expression, and MLC-P were all significantly increased in mesenteric arteries in untreated SHR compared with WKY rats. Early captopril treatment in SHR significantly inhibited Ras and MLCK expression at all ages and decreased ERK-P and MLC-P at 12 and 18 weeks in mesenteric arteries. CONCLUSIONS: These data demonstrate that the antihypertensive effects of captopril are correlated with inhibition of Ras-regulated ERK activation, MLCK expression, and MLC-P.     

Impairment of hypoxic pulmonary artery remodeling by heparin in mice

Chronic hypoxia produces pulmonary artery hypertension and remodeling of pulmonary arteries with hypertrophy of smooth muscle in the media and extension of smooth muscle into more distal small precapillary arteries. The present study investigated the influence of heparin, an inhibitor of platelet-derived growth factor, and of the clotting cascade on this remodeling. Mice maintained in room air or 10% O2 for 26 days were treated with low-dose heparin at 75 units/kg or high dose heparin at 300 units/kg. Pulmonary hypertension and right ventricular hypertrophy developed in the hypoxic mice compared with the room air mice as evidenced by the greater (p less than 0.05) right ventricular systolic pressure (36 +/- 4 SEM versus 21 +/- 1 mmHg) and the increase (p less than 0.05) in right heart weight/left ventricular plus septal weight (35 +/- 1.6 SEM versus 25.2 +/- 1.3). Hypoxia also induced smooth muscle hypertrophy in small pulmonary arteries, with an increase (p less than 0.05) in the percent media thickness/vascular diameter from 5.7 +/- 1 SEM to 13.3 +/- 3 and an apparent decrease (p less than 0.05) in distal small pulmonary arteries from 4.4 +/- 0.2 SEM to 2.05 +/- 0.1 per 100 alveoli. High-dose heparin partially but significantly (p less than 0.05) prevented the pulmonary artery hypertension (right ventricular systolic pressure of 28 +/- 2 mmHg), the right ventricular hypertrophy (right ventricular weight/left ventricular plus septal weight of 30.1 +/- 1) and remodeling of distal small pulmonary arteries (media thickness/vascular diameter of 8.4 +/- 1%, small pulmonary artery/100 alveoli of 3.63 +/- 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cellular hypertrophy in subcutaneous small arteries of patients with renovascular hypertension

Structural alterations of small arteries in patients with essential hypertension are characterized by inward eutrophic remodeling. However, small arteries in patients with secondary hypertension, as well as in experimental models of hypertension with high circulating renin, are characterized by inward hypertrophic remodeling, which is characterized by smooth muscle cell hypertrophy in animal models. The aim of our study was to determine whether remodeling of subcutaneous small arteries in patients with secondary forms of hypertension is associated with smooth muscle cell hypertrophy and/or alterations in the elastic modulus of the vessel wall. Fifteen patients with renovascular hypertension, 9 with primary aldosteronism, and 13 with essential hypertension and 9 normotensive subjects were included in the study. A biopsy of subcutaneous fat was taken from all subjects. Small arteries were dissected, and morphology was determined on a micromyograph. Unbiased estimates of cell volume and number were made in fixed material. From the resting tension-internal circumference relation of the small arteries, the incremental elastic modulus was calculated and plotted as a function of wall stress. Blood pressure was greater in patients with essential hypertension, renovascular hypertension, or primary aldosteronism than in normotensive subjects, but no significant difference was observed among the 3 groups of hypertensive patients. The media/lumen ratio, the medial cross-sectional area, and the smooth muscle cell volume were significantly greater in patients with renovascular hypertension than in normotensive subjects and patients with essential hypertension. No difference in cell number or in the elastic properties was observed among the 4 groups of subjects. In conclusion, our data demonstrate for the first time that a pronounced activation of the renin-angiotensin-aldosterone system is associated with vascular smooth muscle cell hypertrophy in human hypertension in a manner similar to that found in animal models.     

卡托普利治疗后2K1C肾性高血压大鼠心脏和主动脉Gαq/11介导的信号转导通路的变化

目的研究Gαq/11介导的信号转导通路在2K1C肾性高血压大鼠心脏和主动脉中的变化以及卡托普利治疗对其的影响. 方法制备2K1C肾性高血压大鼠模型, 于术后4～8周给予卡托普利(150 mg/kg),观察尾动脉收缩压、左室重与体重之比和主动脉形态学改变.测定心脏和主动脉中Gαq/11含量和磷脂酶C(PLC)活性. 结果 2K1C肾性高血压大鼠在术后4周和8周出现明显的高血压、心肌肥大和主动脉增厚, 心脏和主动脉中Gαq/11含量明显增加.卡托普利治疗4周可以降低血压并逆转心肌肥大, 心脏Gαq/11含量及PLC活性分别降低了15.8%和30.9%, 而主动脉中Gαq/11含量及PLC活性均无变化. 结论 Gαq/11介导的信号转导通路参与2K1C肾性高血压的发生和维持.卡托普利可以逆转心肌肥大, 这一作用可能是通过抑制血管紧张素Ⅱ(Ang Ⅱ)的生成从而消除 Ang Ⅱ导致的Gαq/11介导的信号转导通路的激活而实现的.     

Adrenergic mechanisms and remodeling of subcutaneous small resistance arteries in humans

BACKGROUND: Vascular structural alterations in small resistance arteries of patients with essential hypertension (EH) are mostly characterized by inward eutrophic remodeling. In fact, no difference in the smooth muscle cell volume (CV) between normotensive subjects (NT) and essential hypertensive patients was observed. However, experimental models of hypertension with chronic infusion of agonists of adrenergic receptors were characterized by the presence of smooth muscle cell hypertrophy or hyperplasia. Recently, we have observed the presence of vascular smooth muscle cell hypertrophy in patients with renovascular hypertension. OBJECTIVE: The aim of the study to investigate the structural characteristics of subcutaneous small resistance arteries of NT, of EH, and of patients with phaeochromocytoma (Phaeo). PATIENTS AND METHODS: Thirty Phaeo, 30 NT and 30 EH were included in the study. A biopsy of subcutaneous fat was taken from all subjects. Small resistance arteries (relaxed diameter 160-280 microm) were dissected and mounted on a micromyograph and the media : lumen ratio was calculated. In nine Phaeo, nine NT and 13 EH the cell volume was measured by an unbiased stereological principle, the 'disector' method.RESULTS No difference in smooth muscle cell volume was observed between groups. However, inward remodeling in Phaeo was less marked than in EH, although the increase in media : lumen ratio was similar compared with NT. However, the lack of changes in media cross-sectional area, compared with NT, suggest that there has been little hypertrophy, the changes observed thus being eutrophic. CONCLUSIONS: Our data show, based on a reasonably large sample, that a pronounced activation of the adrenergic system is not associated with vascular smooth muscle cell hypertrophy or hyperplasia in humans. It is therefore possible that adrenergic mechanisms may have a relevant role in the development of eutrophic remodeling in small vessels.