卡托普利对自发性高血压大鼠心血管组织肾素、血管紧张素的影响

为研究卡托普利（ＣＡＰ）对心血管组织肾素─血管紧张素系统的影响，５周龄雄性卒中型自发性高血压大鼠（ＳＨＲｓｐ）随机分为实验组（ｎ＝１２）及对照组（ｎ＝８），分别于食管内喂饲ＣＡＰ（６０ｍｇ·ｋｇ－１／ｄ）或蒸馏水，每日１次，持续８周。用放射免疫法测定血浆肾素活性、血管紧张素Ⅱ（ＡｎｇⅡ），心肌和主动脉平滑肌（ＡＳＭ）的肾素浓度（ＲＣ）和ＡｎｇⅡ含量。结果显示，实验组血压不升高，心室重／体重比值也低于对照组；心肌和ＡＳＭ的ＲＣ比对照组高；而ＡｎｇⅡ被明显抑制，分别为７．０２±０．９６比１３．４０±５．３９（Ｐ＜０．０１）和２４．８０±４．９３比３３．６５±８．８９ｐｇ／ｍｇ蛋白（Ｐ＜０．０２）。这说明，ＣＡＰ长期治疗可明显阻止ＳＨＲｓｐ的血压上升及心肌肥厚的发生，降低心肌和ＡＳＭ中ＡｎｇⅡ含量，提示在这种模型，ＣＡＰ降压及抗心肌肥厚的重要机制之一是阻断心血管组织局部ＡｎｇⅡ的生成。     

缬沙坦对自发性高血压大鼠组织内肾素-血管紧张素的影响

目的     

心脏血管组织肾素血管紧张素系统在自发性高血压大鼠发病中的作用

幼年（5周）及成年（13周）卒中型自发性高血压大鼠（SHPsp）及同龄正常血压WKY大鼠（各组n＝16），乌拉坦麻醉（1．0g／kg，ip），记录颈动脉血压后，取动脉血；剥离心脏以肝素盐水（20IU／ml）港流后取心室肌；剥取主动脉中膜；分别经组织匀浆、提取。以放免法分别测定血浆肾素活性（PRA）及血管紧张素Ⅱ（ATⅡ），心室肌及血管平滑肌（VSM）的肾素浓度（RC）及ATⅡ含量。结果血浆ATⅡ和PRA与SHRsp的血压上升无平行关系，而心血管组织的RC和ATⅡ在SHRsp的幼年组已有增高趋势，至成年则明显高于WKY（P＝0．05～P＜0．01），与血压的升高一致。提示心脏血管组织的RAS与SHRsp高血压的发生和维持有关。     

缬沙坦对自发性高血压大鼠血压和肾素-血管紧张素水平的对照研究

目的:动物实验观察缬沙坦的降压效果及其对血浆肾素活性和血管紧张素Ⅱ的影响.方法:24只雄性14周龄的SHR分为生理盐水组、苯那普利组、小剂量缬沙坦和大剂量缬沙坦组,另用6 只同龄雄性WKY大鼠对照.观察用药4周前后的血压、肾素活性和血管紧张素Ⅱ水平.结果:与生理盐水组、苯那普利组比较,缬沙坦的降压效果明确;大剂量缬沙坦平均下降41.7±4.93 mmHg,明显大于小剂量组的降压幅度27.7±4.46 mmHg,(P <0.01).SHR与WKY大鼠比较,血浆肾素活性仅在大剂量缬沙坦组明显升高;血管紧张素Ⅱ水平,大剂量缬沙坦组更为明显升高,而苯那普利组有所下降.结论:缬沙坦的降压效果优于苯那普利,苯那普利使血浆AngⅡ水平减低,而缬沙坦使血浆AngⅡ水平升高.在长期用药过程中,较高的血浆AngⅡ水平对人体的影响或对器官的影响如何,尚待进一步研究.     

自发性高血压大鼠主动脉平滑肌细胞异常增殖和自身肾素-血管紧张素系统的关系

为探讨自发性高血压大且主动脉平滑肌细胞异常增殖和肾素-血管紧张素系统的关系,用鼠标胸腺嘧啶脱氧核苷掺入量和倍增时间来反映主动脉平滑肌细胞的增殖能力。放射免疫法测定血管紧张素Ⅱ浓度,紫外分光光反法测定血管紧张素转化酶活性。结果发现自发性高血压大且主动脉平滑肌细胞分裂增殖能力比血压正常鼠强,自发性高血压大且主动脉平滑肌细胞肾素-血管紧张素系统处于高功能状态。卡托普利和Sar长期干预可显著抑制自发性高血压大鼠主动脉平滑肌细胞异常增殖,10-4mol/L卡托普利使自发性高血压大及主动脉平滑肌细胞鼠标胸腺嘧啶脱氧核苷掺入量被抑制31%±4%,倍增时间延长13h,血管紧张素Ⅱ和血管紧张素转化酶水平分别下降25%±9%和27%±13%。10-5mol/LSar对自发性高血压大鼠主动脉平滑肌细胞鼠标胸腺嘧啶脱氧核苷掺入的抑制率为20%±3%(p<0.05),倍增时间延长约7h(p<0.05),并使两种大鼠主动脉平滑肌细胞合成和分泌血管紧张素Ⅱ增加(p<0.05),自发性高血压大鼠主动脉平滑肌细胞血管紧张素转化酶活性降低(p<0.05)。卡托普利短期干预不影响两种大且主动脉平滑肌细胞肾素一血管紧张素系统。以上结果提示,卡托普利和Sar长期干预可减少自发性高血压大致主动脉平滑肌细胞血管紧张素Ⅱ生成或阻断血管紧张素Ⅱ与特异性受体结合,从而抑制其异常增殖。     

卡托普利对人离体动脉平滑肌细胞肾素—血管紧张素系统的影响

采用高血压患者的离体脉血管，并分离、培养动脉平滑细胞，观察卡托普利对人ＡＳＭＣ合成和分泌肾素的影响。结果表明，体外培养的ＡＳＭＣ能合成和分泌肾素和血管紧张素Ⅱ。ＥＨ组ＡＳＭＣ及培养液中的肾素活性和ＡｎｇⅡ显著高于正常血压组；ＲＡ和ＡｎｇⅡ与血压呈显著正相关。应用卡托普利后。ＥＨ组的ＡＳＭＣ内ＲＡ显著升高，而ＡｎｇⅡ则明显下降。     

自发性高血压大鼠主动脉平滑肌细胞异常增殖和自身肾素-血管紧张素系统的关系

为探讨自发性高血压大鼠主动平滑肌细胞异常增殖和肾素－血管紧张素系统的关系，用氚标胸腺嘧啶脱氧核苷掺入量和倍增时间来反映主动脉平肌细胞的增殖能力，放射免疫法测定血管紧张素Ⅱ浓度，紫外分光光度法测定血管紧张素转化酶活性。结果发现自发性高血压大鼠主动脉平滑肌细胞分裂增殖能力比血压正常鼠强，自发性高血压大鼠主劝脉平滑肌细胞肾素－血管紧张素系统处于高功能状态，卡托普利和Ｓａｒ长期干预可显著抑制自发性高血压大     

The Mechanism of Distinct Diurnal Variations of Renin-Angiotensin System in Aorta and Heart of Spontaneously Hypertensive Rats

Diurnal variations in plasminogen activator inhibitor-1 mRNA expression are different between the spontaneously hypertensive rats (SHRs) and the Wistar-Kyoto (WKY) rats, and between the aorta and the heart. To elucidate the mechanisms, we examined diurnal changes in the circulating renin-angiotensin system in the SHR and WKY rats. Diurnal variations in plasma renin activity (PRA), plasma angiotensin I, and aldosterone concentrations were similar between the SHR and WKY rats. On the other hand, plasma angiotensin II (Ang II) concentration in the SHR was lower than that in the WKY rats at most time points, but increased to the level of the WKY rats in the late light phase. Treatment with AT1 receptor antagonist candesartan increased plasma Ang II concentration except at ZT 8 and lessened its diurnal variation in the SHR. At the peak in plasma Ang II in the SHR, Ang II regulated genes such as transforming growth factor-β1 and p22phox were upregulated in the aorta. On the other hand, these genes were upregulated throughout the day in the heart of SHR. Candesartan treatment increased AT1a receptor mRNA expression in the heart but not in the aorta of SHR. These findings suggest that an AT1 receptor-mediated mechanism might cause a surge in plasma Ang II concentration at the late light phase in the SHR. Homologous down-regulation of AT1a receptor by Ang II may dampen the effect of a surge in plasma Ang II concentration in the heart of SHR.     

White Blood Cell and Lymphocyte Populations Following Interleukin-2 Administration in the Spontaneously Hypertensive Rat

The immune system has been linked to the pathogenesis of hypertension in the spontaneously hypertensive rat (SHR). Recently interleukin-2 has been reported to inhibit the development of hypertension in the SHR, but no measures of different lymphocyte populations were made. To test the effect of interleukin-2 we repeated the protocol in the report by injecting forty two day old, male SHR and WKY rats, and in addition, analyzed lymphocyte subpopulations. Untreated, age matched rats of the same strain were used as a control. At three and four months of age blood was drawn from all animals. Monoclonal antibodies were used to fluorescently label different lymphocyte subpopulations. The populations examined were the total T-cells, T-nonhelper cells, T-helper cells and B-cells. Total numbers of lymphocytes and white blood cells were also examined. Blood pressures were measured in conscious, restrained animals at two and four months of age. The results showed no attenuation of blood pressure in the interleukin-2 treated SHR at either age. The interleukin-2 treated SHR had a decrease in the percentage of B-cells and an increase in the percentage of T-nonhelper cells relative to the control SHR. Both treated and untreated SHR had increased numbers of white blood cells and lymphocytes compared to both groups of WKY. We conclude that the interleukin-2 used was active but failed to have any effect on blood pressure or absolute numbers of white blood cells and lymphocytes in the treated animals.     

胰激肽原酶对自发性高血压大鼠肾损害的保护作用

背景 胰激肽原酶是一种糖蛋白,作用于激肽原,使之裂解生成激肽,激肽促进内皮细胞释放一氧化氮(NO)与前列腺素I2(PGl2),引起血管扩张、血管渗透性增加,从而发挥降压、保护肾脏、心脏等生理学作用.目的 观察胰激肽原酶干预对自发性高血压大鼠(SHR)肾功能的影响,探讨激肽释放酶激肽系统在高血压及肾脏保护方面的可能机制.方法 36周龄SPF级雄性SHR 12只随机分成高血压对照组(B组)与高血压治疗组[C组,给予胰激肽原酶800 U/(kg·d)灌胃治疗12周],每组各6只.另有年龄匹配的雄性WKY大鼠6只作为正常血压对照组(A组).治疗前、后,观察3组大鼠血压、血肌酐(Scr)、尿素氮(BUN)、NO、6-酮-前列腺素F1a(6-K-PGF1a)及尿微量白蛋白(MAU)、尿β2微球蛋白(β2-MG)、N-乙酰-β-D-氨基葡萄糖苷酶(NAG)浓度及肾脏组织病理改变,并用逆转录聚合酶链反应(RT-PCR)方法测定肾皮质组织型激肽释放酶mRNA的表达.结果 胰激肽原酶治疗后C组血压较B组明显下降(P＜0.01);MAU、β2-MG、NAG定量明显降低(P＜0.01),血清NO、6-K-PGF1a水平升高(P＜0.05);肾皮质组织型激肽释放酶mRNA表达水平增加(P＜0.05).对照组大鼠肾小球小动脉管壁增厚,管腔狭窄,个别小球硬化;胰激肽原酶治疗后肾小动脉结构正常,未见小球硬化.结论 胰激肽原酶能显著减少尿微量蛋白、逆转肾小动脉硬化改变,保护肾功能,其机制可能与血压下降,血清NO、6-K-PGF1a水平及肾脏组织激肽释放酶水平升高有关.     

胰激肽原酶对自发性高血压大鼠肾损害的保护作用

背景胰激肽原酶是一种糖蛋白,作用于激肽原,使之裂解生成激肽,激肽促进内皮细胞释放一氧化氮(NO)与前列腺素I2(PGl2),引起血管扩张、血管渗透性增加,从而发挥降压、保护肾脏、心脏等生理学作用。目的观察胰激肽原酶干预对自发性高血压大鼠(SHR)肾功能的影响,探讨激肽释放酶激肽系统在高血压及肾脏保护方面的可能机制。方法36周龄SPF级雄性SHR12只随机分成高血压对照组(B组)与高血压治疗组[C组,给予胰激肽原酶800U/(kg.d)灌胃治疗12周],每组各6只。另有年龄匹配的雄性WKY大鼠6只作为正常血压对照组(A组)。治疗前、后,观察3组大鼠血压、血肌酐(Scr)、尿素氮(BUN)、NO、6-酮-前列腺素F1a(6-K-PGF1a)及尿微量白蛋白(MAU)、尿β2微球蛋白(β2-MG)、N-乙酰-β-D-氨基葡萄糖苷酶(NAG)浓度及肾脏组织病理改变,并用逆转录聚合酶链反应(RT-PCR)方法测定肾皮质组织型激肽释放酶mRNA的表达。结果胰激肽原酶治疗后C组血压较B组明显下降(P<0.01);MAU、β2-MG、NAG定量明显降低(P<0.01),血清NO、6-K-PGF1a水平升高(P<0.05);肾皮质组织型激肽释放酶mRNA表达水平增加(P<0.05)。对照组大鼠肾小球小动脉管壁增厚,管腔狭窄,个别小球硬化;胰激肽原酶治疗后肾小动脉结构正常,未见小球硬化。结论胰激肽原酶能显著减少尿微量蛋白、逆转肾小动脉硬化改变,保护肾功能,其机制可能与血压下降,血清NO、6-K-PGF1a水平及肾脏组织激肽释放酶水平升高有关。     

自发性高血压大鼠心肌重建反应和卡托普利的保护效应

本研究旨在观察自发性高血压大鼠(SHR)心肌重建反应以及卡托普利的保护作用.通过称重法计算左室重量指数(LVI);使用测微技术,在HE染色切片上测量心肌细胞横径(TDM);运用计算机图像分析技术,在苦味酸天狼猩红染色切片上检测心肌胶原体积比例(CVF)和心肌血管周围胶原面积与管腔面积比例(PVCA).结果显示:15周龄SHR的LVI、TDM、CVA和PVCA均显著高于相应年龄的Wistar-Kyoto大鼠(WKY),但是,卡托普利(100mg/kg/天)治疗12周后,上述参数恢复正常.提示压力负荷下SHR出现了心肌肥大和心肌纤维化,使心肌结构发生了重建;CAP可以逆转心肌肥大和心肌纤维化,因而改善心肌重建.     

Mechanical Properties of Small Femoral Arteries in Spontaneously Hypertensive Rats

The purpose of the study was to compare the mechanical properties of small femoral arteries from spontaneously hypertensive rats (SHR) and normotensive control Wistar-Kyoto rats (WKY) to determine whether these could contribute to the narrowed lumens and thicker medial layers observed during the development of hypertension. Rats were used at either 5,12, or 24 weeks of age. Third order branches of the right femoral artery were mounted in a myograph for morphological measurement and determination of wall mechanical properties. At 5 weeks SHR and WKY arteries were structurally similar but progressive medial thickening and hypertrophy in conjunction with lumenal narrowing was observed in SHR compared with those from WKY in the older rats. However, stress-strain and incremental elastic modulus-stress relationships were similar between strains at all three ages. These data indicate that modifications of arterial wall mechanical properties do not contribute to these progressive arterial structural modifications.     

Stress and High Sodium Effects on Blood Pressure and Brain Catecholamines in Spontaneously Hypertensive Rats

The following experiments were designed to determine if territorial stress, dietary sodium (Na), or the combination of stress and Na effect the rate of development of hypertension in the spontaneously hypertensive rat (SHR 4-18 wks) and if central catecholamines (C) were altered by these treatments. BP was significantly elevated from 2-8 weeks of stress treatment as compared to SHR controls. Norepinephrine (NE) levels in the nucleus tractus solitarius and amygdala (A), and dopamine (D) levels in the hippocampus and A showed significant elevations in the stressed group. High Na (3%) treatment combined with stress treatment produced an even further BP increase and elevated D levels in the amygdala, and elevated NE levels in the area postrema as compared to control SHR's. Selected brain C variables were able to correctly classify animals into high and low BP groups with 90-100% accuracy. Our data support the concept that there are important stress and Na effects upon brain neurochemistry which influence the development of hypertension in the SHR.