丝裂原活化蛋白激酶参与胰岛素对自发性高血压大鼠血管平滑肌细胞的增殖研究

目的:探讨高血压血管平滑肌细胞(VSMC)在胰岛素作用下胞内信号转导途径之一丝裂原活化蛋白激酶(MAPK)的影响,及其与VSMC增殖的关系。方法:选用6周龄自发性高血压大鼠(SHR)和WKY大鼠,无菌分离主动脉,体外纯化培养VSMC至6~8代,加胰岛素干预和蛋白激酶C(PKC)抑制剂,采用胶内髓磷脂碱性蛋白原位磷酸化法测定VSMC中MAPK活性,并用Western Blot检测VSMC中MAPK的含量, [³H]-TdR测定VSMC的DNA合成量。结果:胰岛素作用后,SHR组的DNA合成量显著增加,MAPK活性及蛋白含量也显著增加,PKC抑制剂可明显降低MAPK活性。结论:SHR体外培养的VSMC增殖与MAPK活性增加有关,胰岛素可影响其活性,并且可能存在胰岛素-PKC-MAPK轴。     

胰岛素对自发型高血压大鼠血管平滑肌细胞TGF β及其受体的调节作用

目的:从细胞增生、转化生长因子β₁和受体表达等方面,探讨胰岛素对自发型高血压大鼠血管平滑肌细胞(SHR VSMC)和正常血压Wista-Kyoto大鼠血管平滑肌细胞(WKY VSMC)的影响异同。方法:采用组织移植法培养SHR和WKY大鼠胸主动脉VSMC|用细胞计数仪和流式细胞仪分别检测细胞增生情况|TGF β及其受体的mRNA水平利用定量RT-PCR技术进行检测。结果:(1)胰岛素加强SHR VSMC的增生,而不影响WKY VSMC的增生。胰岛素加强SHR VSMC的增生,且呈剂量依赖方式(2)以20%小牛血清培养基培养VSMC, SHR VSMC的S期百分率为31.44%,而WKY VSMC的S期百分率仅为19.86%|以2%小牛血清培养基培养VSMC,SHR VSMC的G₀／G₁和S期百分率分别为73.23%和9.35%,加入胰岛素后,SHR VSMC的G₀／G₁降低为67.58%,S期百分率则增加到15.64%。但是,加入胰岛素前后,WKY VSMC各期百分率无明显变化|(3)RT-PCR分析结果表明,生长静止的SHR VSMC和WKY VSMC均有TGF β₁、Ⅰ型和Ⅱ型TGF β受体的表达,但SHR VSMC的TGFβ₁、Ⅰ型TGF β受体的表达量高于WKY VSMC的TGF β₁、Ⅰ型TGF β受体的表达量,胰岛素加强了WKY VSMC的TGF β₁、Ⅰ型TGF β受体的表达(P＜0.01和P＜0.05),而削弱了SHR VSMC相应分子的表达(P＜0.01和P＜0.05),胰岛素不影响二株系大鼠VSMC Ⅱ型TGF β受体的表达(P＜0.05)。结论:胰岛素对SHR VSMC和WKY VSMC的TGF β和它的受体表达具有不同的调节作用,这种异常调节作用可能和胰岛素加强SHR VSMC的增生密切相关。     

胰岛素对高血压大鼠血管平滑肌细胞血小板源生长因子A链和转化生长因子β1表达的影响

探讨胰岛素对体外培养的血管平滑肌细胞（VSMC）增生及其长型血小板源生长因子A（PDGF－A）链和转化生长因子β1（TGFβ1）mRNA表达的影响。结果发现：（1）胰岛素促进自发型高血压大鼠的血管平滑肌细胞（SHR－VSMC）增生,且呈浓度依赖性;而对正常血压的Wistar-kyota大鼠的血管平滑肌细胞（WKY－VSMC）增生无影响。（2）定量RT－PCR分析显示,胰岛素加强WKY－VSMC的TGFβ1mRNA的表达（P＜0．01）。但是减少SHR－VSMC的TGFβ1mRNA的表达（P＜0．001）。（3）胰岛素对二株系VSMC的长型PDGF－A上对表达水平无影响。结果表明,胰岛素选择性地加强SHR－VSMC的增殖,而对WKY－VSMC的增殖无影响。这可能和胰岛素能上调WKY－VSMC自分泌TGFβ1有关;而在SHR－VSMC,此反馈抑制失常,结果SHR－VSMC加速生长。     

胰岛素对高血压大鼠血管平滑肌细胞血小板源生长因子A链和转化生长因子β_1表达的影响

探讨胰岛素对体外培养的血管平滑肌细胞 (VSMC)增生及其长型血小板源生长因子A (PDGF A)链和转化生长因子 β1(TGFβ1)mRNA表达的影响。结果发现 :(1)胰岛素促进自发型高血压大鼠的血管平滑肌细胞(SHR -VSMC)增生 ,且呈浓度依赖性 ;而对正常血压的Wistar kyota大鼠的血管平滑肌细胞 (WKY -VSMC)增生无影响。 (2 )定量RT -PCR分析显示 ,胰岛素加强WKY -VSMC的TGFβ1mRNA的表达 (P <0 0 1) ,但是减少SHR -VSMC的TGFβ1mRNA的表达 (P <0 0 0 1)。 (3)胰岛素对二株系VSMC的长型PDGF A链相对表达水平无影响。结果表明 ,胰岛素选择性地加强SHR -VSMC的增殖 ,而对WKY -VSMC的增殖无影响 ,这可能和胰岛素能上调WKY -VSMC自分泌TGFβ1有关 ;而在SHR -VSMC ,此反馈抑制失常 ,结果SHR -VSMC加速生长。     

辣椒素抑制自发性高血压大鼠脑基底动脉平滑肌细胞的增殖和迁移

目的 研究辣椒素(CAP)是否可以改善自发性高血压大鼠(SHR)脑基底动脉平滑肌细胞(BASMC)的增殖迁移。方法 体外培养SHR及Wistar京都(WKY)大鼠原代BASMC,随机均分为对照组(WKY组)、 SHR组、 CAP处理的SHR组。通过CCK-8法选取CAP处理浓度;Transwell^TM小室实验和划痕实验检测各组BASMC的迁移能力;免疫荧光细胞化学染色检测BASMC中的骨桥蛋白(OPN)、增殖细胞核抗原(PCNA)的表达和分布;Western blot法检测BASMC的OPN、 PCNA蛋白水平。结果 与WKY组相比,SHR组BASMC增殖和迁移能力增强,经CAP处理后,细胞增殖和迁移能力降低;OPN表达在BASMC胞质和胞核,PCNA主要表达在胞核,与WKY组相比,SHR组OPN、 PCNA表达及蛋白水平增强,经CAP处理后,其OPN、 PCNA表达及蛋白水平明显降低。结论 CAP可降低SHR来源的BASMC的增殖和迁移。     

葛根素通过p42/44丝裂素活化蛋白激酶途径促进脑微血管内皮细胞增殖

目的:探讨葛根素对自发性高血压大鼠(SHR)脑微血管内皮细胞增殖的影响及其信号转导机制。方法:体外培养SHR及正常血压(WKY)大鼠脑微血管内皮细胞,随机分为(1)WKY对照组:以20%丙二醇孵育24h;(2)SHR对照组:同上处理;(3)葛根素组:SHR内皮细胞以不同浓度(25、50、100ng/L)葛根素分别孵育24h;(4)胎牛血清(FBS)组:SHR内皮细胞以10%FBS孵育24h;(5)PD98059+葛根素组:SHR内皮细胞以丝裂素活化蛋白激酶(MAPKs)抑制剂PD98059(50μmol/L)预孵育10min,再以100ng/L葛根素孵育24h;(6)蛋白磷酸酶激动剂(BDM)+葛根素组:培养的SHR内皮细胞以蛋白磷酸酶激动剂2,3-丁二酮肟(20mmol/L)预孵育10min,再以100ng/L葛根素孵育24h。采用[3 H]-胸腺嘧啶核糖核苷酸([3 H]-TdR)掺入法测定各组细胞增殖,采用免疫印迹法检测各组细胞p42/44MAPKs磷酸化水平。结果:50ng/L和100ng/L葛根素组SHR大鼠微血管内皮细胞[3H]-TdR掺入值较SHR对照组分别高74.1%和96.5%(均P0.05),与FBS组比较差异无统计学意义(P0.05)。PD98059和BDM+葛根素组[3 H]-TdR掺入值分别较100ng/L葛根素组低44.7%和47.5%(均P0.05),与SHR对照组水平无统计学差异(P0.05)。25、50和100ng/L葛根素组p42MAPK磷酸化水平较SHR对照组分别高25.0%、66.7%和75.0%(均P0.05),p44MAPK磷酸化水平较SHR对照组分别高17.8%、60.2%和62.7%(均P0.05)。PD98059和BDM+葛根素组p42MAPK和p44MAPK磷酸化水平均较100ng/L葛根素组明显下调(P0.05),而与SHR对照组差异无统计学意义(P0.05)。结论:葛根素能诱导SHR脑微血管内皮细胞增殖,其细胞内信号转导可能与p42/44MAPKs磷酸化途径有关。     

卡格列净改善自发性高血压大鼠主动脉重构的作用及其机制

目的：探索卡格列净通过调控血管平滑肌细胞（VSMCs）增殖迁移及肾素-血管紧张素-醛固酮系统（RAAS）/转化生长因子β1(TGF-β1)信号通路,改善自发性高血压大鼠（SHR）胸主动脉重构。方法 ：将大鼠分为正常血压大鼠对照组（WKY组）、SHR组和SHR+卡格列净组。尾袖血压计监测大鼠尾动脉血压,H-E染色评估胸主动脉血管壁中膜厚度及中膜厚度/管腔直径比值,Masson染色检测血管壁纤维化程度。体外分离培养WKY和SHR胸主动脉VSMCs,细胞分为WKY组、WKY+卡格列净组、SHR组和SHR+卡格列净组。CCK-8检测细胞增殖,划痕实验检测细胞迁移,RT-qPCR和免疫印迹检测α-平滑肌肌动蛋白（α-SMA）、分泌型磷酸蛋白1(SPP1)、 I型胶原蛋白（Col1a）、Ⅲ型胶原蛋白（Col3a）、血管紧张素原（AGT）、血管紧张素Ⅱ受体1 (AGTR1)、TGF-β1mRNA与蛋白表达。结果 ：给予卡格列净灌胃8周后,与SHR组相比,SHR+卡格列净组大鼠尾动脉血压、胸主动脉中膜厚度、中膜厚度/管腔直径比值、胶原蛋白沉积程度降低。SHR组VSMCs增殖、迁移能力较WKY组明显增强...     

吡格列酮对自发性高血压大鼠心脏成纤维细胞胶原合成的研究

目的观察胰岛素增敏剂吡格列酮(PIO)对培养的自发性高血压大鼠(SHR)和WKY大鼠的心脏成纤维细胞(CFs)胶原合成以及一氧化氮合酶-一氧化氮(NOS-NO)的影响。方法采用胶原酶消化法培养SHR和WKY的CFs,羟脯氨酸比色法测定CFs培养上清胶原含量,硝酸还原酶法测定CFs培养上清NO浓度,分光光度计法测定CFs培养上清NOS活性。结果(1)在不同浓度及不同时间点的PIO干预下,SHR和WKY的CFs上清羟脯氨酸含量均较对照组明显降低,差异具有显著性(P<0.01)。(2)5×10-6mol/L的PIO干预48h,SHR和WKY的CFs培养上清NO浓度、NOS活性均较各自对照组明显上升,差异非常显著(P<0.001)。结论PIO呈浓度和时间依赖性的方式抑制SHR的CFs的胶原合成,上调NOS-NO水平。     

罗格列酮增强胰岛素所致自发性高血压大鼠心肌细胞变力效应

目的 :观察自发性高血压大鼠 (SHR)心肌细胞收缩 /舒张功能及细胞内钙瞬变对胰岛素反应性的改变 ,并进一步探讨γ -过氧化物酶体增殖剂活化受体 (PPARγ)激活剂罗格列酮 (rosiglitazone ,ROSI)对SHR心肌细胞胰岛素敏感性的影响。方法 :雄性WistarKyoto大鼠 (WKY)和SHR ,随机分为下列 4个处理组 :①WKY对照组 ,②WKY +胰岛素 (10 -7mol/L) ,③SHR +胰岛素 ,④SHR +ROSI(3mg·kg-1·d-1,op ,预处理 14d) +胰岛素。常规酶解法分离制备钙耐受心肌细胞 ,以含氧台氏液灌流并予电场刺激 (0 5Hz,5ms) ,采用可视化动缘探测系统 (vid…     

PI3K-ERK信号在胰岛素诱导的血管平滑肌细胞增殖中的作用

目的： 探讨胰岛素促血管平滑肌细胞增殖的分子机制。方法: 原代培养的SD大鼠血管平滑肌细胞为研究对象,［3H］-TdR掺入实验观察胰岛素刺激后血管平滑肌细胞的增殖,免疫印迹分析PI3K－ERK信号在平滑肌细胞增殖中的作用。结果: 胰岛素明显促进血管平滑肌细胞增殖,该作用呈现剂量依赖性关系,PI3K抑制剂LY294002、MAPK抑制剂PD98059可抑制胰岛素的促增殖作用,［3H］-TdR掺入分别下降48.8%、43.6%,抑制PI3K可下调胰岛素刺激的磷酸化ERK1/2蛋白表达和ERK活性,分别下降112％、127％。结论: PI3K－ERK1/2信号通路参与了胰岛素促平滑肌细胞增殖过程。     

阿托伐他汀影响自发性高血压大鼠血压的机制探讨

目的：探讨阿托伐他汀控制自发性高血压大鼠（SHR）高血压的机制，研究阿托伐他汀对SHR血浆内皮素-1（ET-1）和主动脉一氧化氮合酶（NOS）的影响，以及对SHR的主动脉平滑肌细胞（ASMC）凋亡和P27蛋白表达的影响。 方法： 选用8周龄SHR 12只，随机分为阿托伐他汀治疗组（ATV组, n=6）和SHR组（n=6），并以同周龄WKY（n=6）作为对照。ATV组给以阿托伐他汀（50 mg·kg-1·d-1）灌胃。10周后观察3组大鼠血压、血清总胆固醇（TC）、总甘油三酯（TG）含量变化，血浆ET-1和主动脉NOS活性的改变，以及TUNEL法检测ASMC凋亡率，测定动脉ASMC P27蛋白表达。 结果： 阿托伐他汀给药10周后，ATV组动脉收缩压显著低于SHR组［（134.17±3.60）mmHg vs （173.33±3.78）mmHg, P<0.01］；ATV组血清TC和TG浓度均显著低于SHR组（P<0.01, P<0.01）。同时，阿托伐他汀显著降低SHR血浆ET-1水平［（130.04±40.07）ng/L vs （196.74±59.69）ng/L，P<0.05］和增加SHR主动脉NOS活性［(0.189±0.040）kU/g protein vs （0.124±0.057）kU/g protein，P<0.01］；ATV组ASMC凋亡率显著高于SHR组（16.94%±3.08% vs 9.01%±2.36%, P<0.01）；ATV组ASMC P27蛋白表达阳性率显著高于WKY大鼠（33.02%±5.01% vs 24.25%±4.41%, P<0.05），而SHR组该指标明显低于WKY大鼠（16.08%±7.09% vs 24.25%±4.41%, P<0.05）。 结论： 阿托伐他汀控制SHR血压增高，其机制可能与降低SHR的血浆ET-1水平和增高主动脉NOS活性，以及增高ASMC凋亡率和P27蛋白表达阳性率有关。     

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。     

依那普利对自发性高血压大鼠心肌ACE和ACE2表达的影响

 目的 观察自发性高血压大鼠(spontaneously hypertensive rats, SHR)心肌的血管紧张素转换酶(angiotensin-converting enzyme, ACE)和ACE2的表达,以及依那普利干预的影响。方法 将15只SHR随机分为2组：SHR对照组(n=7)和依那普利组(n=8),分别给以安慰剂、依那普利15mg.kg-1.d-1灌胃干预4周。干预结束后处死大鼠,分离左心室,行RT-PCR、western blot蛋白质免疫印迹检测。同步取10只WKY大鼠作为正常血压对照组。结果SHR心肌的ACE的mRNA和蛋白质的表达都显著高于)WKY组(1.68±0.34 vs 0.33±0.12, P＜0.05;1.21±0.14 vs 0.71±0.11, P＜0.05),而ACE2 的mRNA和蛋白质表达皆明显低于WKY组(0.50±0.15 vs 1.16±0.24, P＜0.05; 0.71±0.24 vs 1.22±0.14, P＜0.05)。依那普利明显降低ACE的mRNA和蛋白质表达(0.44±0.19 vs 1.68±0.34, P＜0.01; 0.87±0.13 vs 1.21±0.14, P＜0.05),提升ACE2的mRNA表达(1.77±0.49 vs 0.50±0.15, P＜0.05),对ACE2的蛋白表达无明显影响(0.42±0.22 vs 0.71±0.24, P＞0.05)。结论 SHR心肌ACE明显升高,ACE2显著降低,有利于血压上调。依那普利能降低ACE,提升ACE2,可能是血管紧张素转换酶抑制剂(angiotensin-converting enzyme inhibitors, ACEI)的降压机制之一。     

高糖及高胰岛素对人血管平滑肌细胞增殖、迁移及miR-145水平的影响

目的探讨高血糖和高胰岛素对人miR-145水平的影响。方法将人血管平滑肌细胞(VSMC)分为正常组、高糖组(25 mmol/L)、高胰岛素组(300 m U/L)和高糖高胰岛素组,各组细胞培养72 h后,用real-time PCR测定各组VSMC中miR-145的水平;用四甲基偶氮唑盐(MTT)法及细胞划痕法分别测定VSMC的增殖及迁移。miR-145病毒转染VSMC 48 h后,再分为上述4组,用上述方法测定病毒转染后VSMC的增殖与迁移。结果与正常组相比,其他3组miR-145水平均不同程度下降(P0.05),尤以高糖高胰岛素组下降最明显(P0.01);高糖及高胰岛素促进VSMC的增殖和迁移。miR-145病毒转染后,各组VSMC的增殖和迁移均较转染前明显降低(P0.05)。结论高血糖及高胰岛素降低VSMC中miR-145的表达,miR-145的过表达可抑制VSMC的增殖和迁移。     

氯沙坦逆转高血压大鼠阻力血管重塑的实验研究

目的:探讨氯沙坦对自发性高血压大鼠(SHR)阻力血管重塑的影响。方法:将雄性SHR20只随机分为氯沙坦治疗组和SHR对照组。另选同系雄性WKY大鼠10只作为正常对照组。治疗组给予氯沙坦30mg/kg/天,溶于饮水灌胃治疗17周。颈动脉插管,心电血流动力学监护仪测定动脉收缩压,应用计算机图像分析,计算血管壁腔面积比,用光镜和透射电镜观察SHR肠系膜动脉三级分支结构的变化;血浆放免法测肾素活性和血管紧张素Ⅱ(AngⅡ)含量。结果:氯沙坦治疗组的血管壁腔面积比与SHR对照组相比有所降低(P<0.05),但与WKY相比有所升高(P<0.05);血浆肾素活性在WKY组和SHR对照组之间无明显差异(P>0.05),治疗组肾素活性高于SHR对照组(P<0.05);治疗组的AngⅡ水平高于SHR对照组(P<0.01)。结论:氯沙坦具有逆转SHR血管重塑的作用。     

肾上腺髓质素加强高糖对自发性高血压大鼠胰岛β细胞的毒性作用

探讨高糖是否对自发性高血压大鼠 (SHR)和 Wistar- Kyoto(WKY)鼠胰岛 β细胞分泌功能具有抑制作用 ,肾上腺髓质素 (adrenomedullin,AM)能否加强此抑制作用。选取 6周龄 SHR鼠及 10周龄 WKY鼠各 10只 ,分离胰岛放入 12孔培养板内 (90个胰岛 /孔 )培养。先以含 5 .6 m mol/ L(m M)葡萄糖的 RPMI16 4 0培养基培养 1h,取出培养液。然后用含 2 0 m M葡萄糖及不同浓度 AM(分别是 0 ,10 - 8,10 - 7,10 - 6 M)的 RPMI 16 4 0培养基培养 1小时 ,取出培养液 ,放射免疫分析 (RIA)方法测定两次培养液的胰岛素含量。 SHR鼠的胰岛细胞经用不加 AM含 2 0m M葡萄糖的 16 4 0培养基培养 1h后 ,与用含 5 .6 m M葡萄糖的 16 4 0培养基培养 1h相比 ,其培养液中胰岛素含量明显降低 (分别是 19.9± 6 .6 vs6 0 .9± 33.6 m U/ L,P<0 .0 5 )。当用含 2 0 m M葡萄糖及不同浓度 AM的 16 4 0培养基培养时 ,随着 AM浓度的增加 ,培养液中的胰岛素含量进一步减少 (19.9± 6 .6 vs2 2 .2± 8.0 vs2 1.5± 5 .6 vs17.9± 3.6 m U/ L)。对照组 WKY鼠的胰岛细胞经上述相同方法处理后得出相似的结果。但 WKY鼠与 SHR鼠相比 ,其胰岛细胞经用含 5 .6 m M及 2 0 m M葡萄糖培养基培养后培养液中的胰岛素含量较高 (P<0 .0 1)。用高糖培养基培养     

The effects of beta adrenoceptor blockade with atenolol on myocardial cellular and subcellular hypertrophy in spontaneously hypertensive rats

In this study we investigated the effects of chronic β adrenoreceptor blockade with atenolol on cellular and subcellular hypertrophy in spontaneously hypertensive rats (SHR). Atenolol was injected subcutaneously (20 mg/kg) twice daily commencing in four-week-old rats. The treated animals (SHR-A) were compared to their nontreated controls and normotensive, Wistar-Kyoto (WKY) controls at the age of 16 weeks. A group of atenolol-treated WKY was also studied. Chronic drug treatment was effective in attenuating the rise in systolic blood pressure characteristic of SHR, but did not normalize the values to those of WKY. Cardiac hypertrophy, characteristic of SHR, was modified by drug treatment as evidenced by left ventricular weights as well as myocardial cell size. The cells from the subendocardium underwent selective hypertrophy in SHR which was attentuated by about 50% after atenolol treatment. Stereological analysis of electron micrographs showed that while relative mitochondrial volume was not affected by treatment, relative myofibrillar volume (%) decreased in both subepicardium (SHR = 63.28 ± 1.25; SHR-A = 56.72 ± 1.37) and subendocardium (SHR = 66.53 ± 1.27; SHR-A = 58.30 ± 1.51). This change raised the mitochondrial/myofibrillar volume ratio, which is characteristically low in SHR compared to WKY. Sarcoplasm, which included all cell constituents except mitochondria, increased with atenolol treatment, but water concentration remained unchanged. The data suggest that attenuation of hypertrophy in SHR after β blockade is associated with selective effects on the myocardial cell involving primarily the myofibrillar cell compartment.     

Interaction between “mental stress” and baroreceptor reflexes concerning effects on heart rate,mean arterial pressure and renal sympathetic activity in conscious spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were compared concerning the interactions between cortico-hypothalamic alerting responses and baroreflex influences on neurogenic cardiovascular control. For this purpose mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were continuously recorded during night time in conscious, otherwise undisturbed rats. Baroreceptor sensitivity was assessed as percentage HR and RSNA reductions per mmHg MAP elevation when a standardized phenylephrine infusion was performed. A state of acute “mental stress” could be induced by a likewise standardized sudden blowing of air. These two opposing influences on neurogenic cardiovascular control were also experimentally superimposed in various ways and the effects on MAP, HR and RSNA followed. During “rest” RSNA was higher in SHR than in WKY and it also increased more during “mental stress”. The baroreflex sensitivity was clearly reduced in SHR and WKY concerning HR reduction (0.44±0.06 vs. 0.78±0.08%/mmHg; p<0.01) but not so concerning RSNA, which was similar in SHR and WKY (2.6±0.2 vs. 2.9±0.4%/mmHg). If expressed (HR + 1±3%; p<0.025 vs. SHR and RSNA + 11%±10, p<0.01 vs. SHR). These results) (0.10±0.02 vs. 0.06±0.01 μV/mmHg; p<0.12). Also single fibre recordings in anaesthetized rats showed the same principle difference between SHR and WKY. Addition of “mental stress” during phenylephrine baroreflex activation clearly increased both HR (24±7%) and RSNA (114±21 %) in SHR, while almost no change then occurred in WKY (HR + 1±3%; p<0.025 vs. SHR and RSNA + 11%±10, p<0.01 vs. SHR). These results suggest that a modestly accentuated cortico-hypothalamic activity ordinarily prevails in SHR, explaining the suppressed baroreflex control of heart rate and the augmented sympathetic activity to e.g. renal and splanchnic areas. Further, environmental alerting stimuli induce in SHR more powerful defence reactions which, unlike the situation in WKY, readily overcome baroreflex inhibitory influences on sympathetic activity.     

Migration of vascular smooth muscle cells is enhanced in cultures derived from spontaneously hypertensive rat

 Migration of vascular smooth muscle cells (SMC) constitutes a common step in neointimal formation which occurs in several vascular diseases. Whether the migratory response of SMC derived from hypertensive animals is different to that of controls may provide a clue to the link between hypertension and atherosclerosis. We examined the migratory responses of SMC from cell cultures and ring explants (thin aortic ring segment) and compared these responses between normotensive and hypertensive rats at two different ages. Both scrape-wound assay and transwell chambers from cultured aortic SMC as well as aortic ring explant cell outgrowth models were employed. The aortae were obtained from male spontaneously hypertensive rats (SHR) and their normotensive counterpart the Wistar-Kyoto rat (WKY) at 5 and 20 weeks of age. Migration was induced by fetal bovine serum or platelet-derived growth factor (PDGF) and migrated cells were counted at different times following stimulation. We found that SMC migration exhibited a high sensitivity to serum (range of ED₅₀: 2.2–3.6%), migration of SMC from 20-week-old SHR exceeded (by 46%, P<0.025) that of SMC from age-matched WKY and the difference became significant as early as 8 h after stimulation by serum. Chemotaxis induced by PDGF (2 h) exhibited similar differences. An elevated migratory response in SHR-SMC was also found in cells derived from 5-week-old rats in whom the blood pressure was normal. In younger animals, cell outgrowth from SHR aortic ring explants also accumulated more cells compared with WKY without a higher growth rate, thus suggesting that SHR-SMC have a higher migratory response ex vivo. In conclusion, aortic SMC migration appeared to be enhanced in various preparations from SHR. This difference also existed in young animals before the elevation of blood pressure occurred and might contribute partly to the role of hypertension as a risk factor for atherosclerosis. Received: 2 April 1997 / Received after revision: 2 September 1997 / Accepted: 8 September 1997