自发性高血压大鼠血浆和主动脉组织甘丙素浓度的变化及巯甲丙脯酸对它的影响

用放射免疫分析测定了自发性高血压大鼠（ＳＨＲ）和对照组ＷＫＹ大鼠血浆和胸主动脉组织的甘丙素（ｇａｌａｎｉｎ）含量，同时观察血管紧张素转换酶抑制剂──巯甲丙脯酸对它的影响。ＳＨＲ血浆和胸主动脉组织甘丙素含量显著高于ＷＫＹ大鼠的（Ｐ＜０．０５～０．０１）．滴注巯甲丙脯酸后ＳＨＲ血压下降４９％（Ｐ＜０．０５），血浆甘丙素下降３％（Ｐ＜０．０１），主动脉组织甘丙素下降１９％。结果揭示甘丙素在高血压病的发病学中可能具有重要意义。     

去甲肾上腺素促使血管平滑肌细胞内三磷酸肌醇含量的增加

研究去甲肾上腺素（ＮＥ）对自发性高血压大鼠（ＳＨＲ）的主动脉血管平滑肌细胞（ＶＳＭＣｓ）内三磷酸肌醇（ＩｎｓＰ３）含量的影响，并与对照组京都威斯特大鼠（ＷＫＹ）相比较，结果显示，在基础状态下ＳＨＲ和ＷＫＹ的ＶＳＭＣｓ内ＩｎｓＰ含量针明显差异，ＮＥ作用下ＷＫＹ的ＶＳＭＣｓ内ＩｎｓＰ３值迅速增加，１０秒钟同即达高峰，而ＳＨＲ的ＶＳＭＣｓ内ＩｎｓＰ３的增加呈双相性，除快相峰值明显大于ＷＫＹ外，慢相峰值也     

高血压大鼠视网膜组织Ca^2＋酸性磷酸酶组织化学的研究

目的：应用光镜定量酶组织化学方法对正常京都种大鼠（ＷＫＹ）和自发性高血压大鼠（ＳＨＲ）视网膜组织的Ｃａ＾２＋－酸性磷酸酶的分布和活性进行定量观察，结果：Ｃａ＾２＋酸性磷酸酶在ＷＫＹ视网膜组织的活性由强到弱依次为（Ｆ检验，Ｐ〈０．０５）；（１）杆锥细胞内节和外核层；（２）节细胞层；（３）内核层；（４）内网层和外网层；（５）杆锥细胞外节阴性，在ＳＨＲ视网膜组织中，各层Ｃａｓ＾２＋酸性磷酸酶活性下降，以     

SHR血浆NPY、主动脉平滑肌细胞NPY受体的变化及药物的干预作用

目的：观察自发性高血压大鼠（ＳＨＲ）血浆神经肽Ｙ（ＮＰＹ）、血管平滑肌细胞（ＶＳＭＣ）ＮＰＹ受体的变化及美托洛尔、培哚普利干预的影响。方法：用放射免疫分析法和受体放射配体结合分析法测定血浆ＮＰＹ及ＶＳＭＣ上ＮＰＹ受体密度的变化。结果：ＳＨＲ血浆ＮＰＹ含量明显高于ＷＫＹ，血压的高低与血浆ＮＰＹ的量呈明显的正相关。培哚普利降压的同时亦降低ＳＨＲ血浆ＮＰＹ的量，而美托洛尔对ＮＰＹ量则无影响；培哚普利引起     

卒中型高血压大鼠心肌线粒体Ca~（2＋），Mg~（2＋）—ATPase及膜流动

本文比较了卒中型自发往高血压鼠（ＳＨＲｓｐ）和京都Ｗｉｓｔａｒ正常血压鼠（ＷＫＹ）心肌线粒体Ｃａ￣（２＋），Ｍｇ￣（２＋）－ＡＴＰａｓｅ活力及膜流动性。用定磷法测得ＷＫＹ和ＳＨＲｓｐ的Ｃａ￣（２＋），Ｍｇ￣（２＋）－ＡＴＰａｓｅ活力（２５℃）分别为０．２８７±０．０１６及０．２１８±０．０１７μｍｏｌ／（ｍｉｎ．ｍｇ）（－ｘ±Ｓｘ）。ＳＨＲｓｐ心肌线粒体Ｃａ￣（２＋），Ｍｇ￣（２＋）－ＡＴＰａｓｅ活力降低２４．７％，两组比较有显著差异（Ｐ＜０．０１，ｎ＝９）．以ＤＰＨ标记心肌线粒体膜，测得ＷＫＹ和ＳＨＲｓｐ的荧光偏振值分别为０．１８７±０．００３及０．１８１±０．００３（Ｐ＞０．０５，ｎ＝６）。     

自发性高血压大鼠左心室肥厚与局部胰岛素样生长因子Ⅰ的关系

目的和方法：采用放射免疫分析法测定自发性高血压大鼠（ＳＨＲ）和正常血压大鼠（ＷＫＹ）心肌组织中胰同素样生长因子Ⅰ（ＩＧＦ－Ｉ）水平,用心肌细胞横径（ＴＤＭ）和心脏湿重／体重（ＨＷ／ＢＷ）判定左心室肥厚。结果：ＳＨＲ的ＴＤＭ和ＨＷ／ＢＷ均十分显著的高于ＷＫＹ;心肌组织ＩＧＦ－Ｉ水平也显著高于ＷＫＹ,且ＳＨＲ心肌组织ＩＧＦ－１与ＴＤＭ及ＨＷ／ＢＷ之间均呈显著正相关。结论：ＳＨＲ有明显的左心室肥厚,而组     

自发性高血压大鼠心瓣膜上含神经肽Y和含降钙素基因相关肽神经的变化

用免疫组织化学（ＡＢＣ）方法，观察了含神经肽Ｙ（ＮＰＹ）、降钙素基因相关肽（ＣＧＲＤ）神经在自发性高血压大鼠（ＳＨＲ）心瓣膜分布的变化。结果表明，在ＳＨＲ二尖瓣、三尖瓣上含ＮＰＹ、含ＣＧＲＰ神经的密度，和对照Ｗｉｓｔａｒ－Ｋｙｏｔｏ（ＷＫＹ）大鼠相比较，无明显差异。但ＳＨＲ二尖瓣及三尖瓣含ＮＰＹ神经的Ｒ值，即心壁和乳头肌两个来源的含肽神经相延续所在的腱索数目与本片瓣膜上的总腱索数的比值，大于ＷＫＹ大鼠；而ＳＨＲ心瓣膜含ＣＧＲＰ神经的Ｒ值和ＷＫＹ大鼠无差异。本文对ＳＨＲ心瓣膜上含ＮＰＹ和含ＣＧＲＰ神经的变化作了讨论。     

内皮素A受体拮抗剂BQ123降压作用的研究

为探讨内皮毒在机体血压调节中的意义，本文观察ＥＴＡ受体拮抗剂ＢＱ１２３的降压作用。静脉注射ＢＱ１２３（０．１，１和２ｍｇ／ｋｇ）后，自发性高血压大鼠（ＳＨＲ）和正常血压大鼠（ＷＫＹ）血压呈剂量依赖地降低，持续４０～６０分钟。ＢＱ１２３对ＳＨＲ的降压作用强于ＷＫＹ。给Ｗｉｓｔａｒ大鼠静脉注射ＢＱ１２３呈剂量依赖地拮抗外源性ＥＴ－１（２×１０＾－９ｍｏｌ／ｋｇ）引起的血压升高反应。在培养的ＳＨＲＢＱ１     

正常血压和高血压大鼠下丘脑室旁核微灌注氨肽酶

正常血压和高血压大鼠下丘脑室旁核微灌注氨肽酶ＢａｔＣｍ，ｅｔａｌ．ＢｒａｉｎＲｅ┐ｓｅａｒｃｈＢｕｌｅｔｉｎ．１９９６，３９（４）２３５～２４０给正常血压实验大鼠（ＷＫＹ）和自发性高血压大鼠（ＳＨＲ）下丘脑（ＰＶＮ）室旁核注入氨肽酶（ＡｍＭ），记录麻...     

正常血压和高血压大鼠下丘脑室旁核微灌注氨肚酶

正常血压和高血压大鼠下丘脑室旁核微灌注氨肚酶ＢａｔｔＣｍ，ｅｔａｌ．ＢｒａｉｎＲｅｓｅａｒｃｈＢｕｌｌｅｔｉｎ．１９９６，３９（４）２３５～２４０给正常血压实验大鼠（ＷＫＹ）和自发性高血压大鼠（ＳＨＲ）下丘脑（ＰＶＮ）室旁校注人氨肽酶（ＡｍＭ），记录...     

自发性高血压大鼠肾动脉的零应力状态

通过观察动脉主干张开角的大小,研究了自发性高血压大鼠（Ｓｐｏｎｔａｎｅｏｕｓｌｙ ｈｙｐｅｒｔｅｎｓｉｖｅ,ｒａｔ,ＳＨＲ）高血压建立后肾动脉零应力状态的变化,并于ＳＨＲ高血压形成前,分别给予口服型ＡｎｇⅡ Ⅰ型受体拮抗剂Ｌｏｓａｒｔａｎ和ＥＴ Ａ型受体拮抗剂ＢＭＳ－１８２８７４,研究内源性ＡｎｇⅡ和ＥＴ在ＳＨＲ肾动脉零应力状态变化中的作用。 现,在高血压已建立的ＳＨＲ,肾动脉主干张开角（１１４．     

原发性高血压与应激性高血压大鼠NO/NOS、ET的变化

目的：探讨强物理因子诱发高血压后，一氧化氮（NO）／一氧化氮合酶（NOS）系统和内皮素（ET）的作用。方法：电击大鼠足底结合噪音刺激制作慢性应激性高血压大鼠（CSHR）模型，采用特异性放射免疫测定技术和化学比色法，检测原发性高血压大鼠（SHR）和正常血压（Wistar-kyoto WKY）大鼠，以及CSHR和正常血压Wistar大鼠心肌ET、NO和NOS的含量。结果：（1）SHR的尾动脉收缩压（CASP），左心室重量指数（LVW／BW）明显高于WKY大鼠（P〈0．01）。SHR的心肌ET水平明显高于WKY大鼠（P〈0．05）。（2）CSHR的CASP明显高于Wistar大鼠（P〈0．01），而LVW／BW及右心室重量指数（RVW／BW）与Wistar大鼠无差异（P〉0．05）。CSHR的心肌ET水平明显高Wistar大鼠（P〈0．01），而心肌NO及NOS水平则低于Wistar大鼠（P〈0．05）。结论：ET的增多以及NO／NOS系统功能低下可能参与了自发性高血压与慢性应激性高血压的发生和发展。NO／NOS系统和ET可能参与了SHR心肌肥厚的发生和发展。在CSHR中，应激四周可以造成血压升高，ET增多以及NO／NOS系统功能低下，但来发生心肌肥厚。     

Age-series characteristics of locomotor activities in spontaneously hypertensive rats: a comparison with the Wistar-Kyoto strain

This study was to investigate the behavioral specificities of spontaneously hypertensive rats (SHR) and compare them with Wistar-Kyoto (WKY) controls using a 1-year longitudinal study of locomotor activity. Rat locomotor activity was examined every week at 4-12 weeks of age and every month at 4-12 months of age using an Automated Digiscan Activity Monitor system. Six behavioral variables were collected and analyzed: horizontal activity (HA), total distance (TD), movement time (MT), vertical activity (VA), stereotypy count (SC), and margin time (MGT). In general, a significant weekly and monthly age-dependent change (p<0.01) in SHR was shown in the HA, TD, VA, SC and MT variables, whereas MGT showed no significant differences (p>0.05). However, except for the first observations, SHR was significantly hyperactive relative to WKY for HA, VA, TD, MT and SC (p<0.01) before 6 months of age. MGT in SHR were significantly lower than those of WKY (p<0.01) before 3 months of age. Only for VA, SHR was more hyperactive than WKY (p<0.01) and sustained for 12 months in age. From the present results, by extending the observations of locomotor activity testing from 4 weeks to 12 months of life, we were able to observe an interesting strain difference between SHR and WKY in the development pattern of spontaneous activity levels.     

Tissue and blood magnesium levels in spontaneously hypertensive rats, at rest and in stressful conditions

Magnesium (Mg) levels were measured by flame atomic absorption spectrophotometry in the blood (plasma, erythrocytes) and soft tissues (liver, brain, heart, aorta, kidneys, adrenals, spleen, thymus) of adult spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar Kyoto (WKY). In experiment 1, Mg determinations were performed on eight animals of each strain at rest. Mg levels were lower in brain (P less than or equal to 0.05), kidneys (P less than or equal to 2.10(-4] and erythrocytes P less than or equal to 0.01) in SHR than in WKY rats. Tissue water content was the same in the two strains. These results suggest the occurrence of lower intracellular Mg levels in SHR than in WKY. In experiment 2, 15 SHR and 15 WKY were submitted either to acute (1 d) or subacute (22 d) stresses or reared in restful conditions. Acute stress induced important Mg shifts leading to a decreased difference between SHR and WKY in most tissues and to an increased and more significant difference (P less than or equal to 0.01) in spleen and plasma Mg levels. Subacute stress was milder and had little effect. It is concluded that the results of experiment 1 cannot be attributed to the greater sensitivity of SHR to laboratory manipulations. When compared with previously published data our results nevertheless suggest an association between stress sensitivity and genetic factors regulating Mg metabolism.     

SHR大鼠血压升高前后脑内VEGF的变化及其意义

为探讨自发性高血压大鼠(SHR)血压升高前后脑内血管内皮生长因子(VEGF)表达水平的变化及其意义,本研究应用免疫组化SP法及计算机图像分析技术,对幼年(6周龄)和成年(12月龄)SHR大鼠及幼年(6周龄)和成年(12个月龄)同品系正常血压对照组京都Wistar大鼠(WKY)脑切片VEGF蛋白的表达水平进行了定量分析。结果发现在4组大鼠大脑皮质的广泛区域、纹状体、室管膜上皮及脉络丛等处均观察到散在分布的VEGF样免疫阳性细胞,阳性反应产物呈棕色颗粒状,位于胞浆中,其中幼年和成年WKY及幼年SHR三组间阳性细胞数及其灰度差异无显著性(P>0.05),而12月龄SHR组阳性细胞数及其灰度均高于其它三组(P<0.05)。以上结果提示:随着成年SHR大鼠血压的升高,脑内VEGF蛋白的表达水平上调,高表达的VEGF可能对高血压时脑缺血缺氧诱导的血管内皮细胞凋亡及微血管的存活有保护意义,同时也可能参与了高血压所致的脑损伤。     

一氧化氮合酶在自发性高血压大鼠视上核及室旁核的分布

目的：探讨自发性高血压大鼠视上核及室旁核内一氧化氮合酶阳性神经元的改变。方法：用ＮＡＤＰＨ－ｄｉ－ａｐｈｏｒａｅ组织化学方法,观察和比较了一氧化氮合酶在自发性高血压大鼠和正常对照大鼠视上核和室旁核的分布间下观察下捕脑视上核及室旁核的一氧化氮合酶阳性细胞形态、分布并进行计数。用图像分析仪测其灰度显差异。视上核及室旁核内的一氧化氮合酶阳性细胞灰度值在高血压组均明显高于对照组。提示这两上核内一氧化氮合酶     

阿托伐他汀对自发性高血压大鼠细胞色素P450羟化酶基因表达的影响

目的： 评价阿托伐他汀对自发性高血压大鼠（SHR）血压和细胞色素P450羟化酶(CYP)4A1的调节作用。方法： 18只SHR随机分为3组：SHR对照组、阿托伐他汀50 mg组(HATV组)和10 mg组(LATV组)；6只Wistar-Kyoto大鼠(WKY)作为正常对照组。给药共10周,分别于给药前和给药后每2周测量大鼠尾动脉收缩压(SBP)；RT-PCR、Western blotting法检测心、肝、肾及主动脉中CYP4A1 mRNA和蛋白质表达；并测定血脂含量。结果： 用药前SHR各组SBP均显著高于WKY组(P<0.01)；HATV组在给药后第6、8、10周和LATV组在给药后第10周SBP明显低于SHR对照组(P<0.05或P<0.01)。在CYP4A1 mRNA及其蛋白质表达中，SHR对照组4种组织均明显高于WKY组(P<0.01或P<0.05)；给药10周后，HATV组心、肾及主动脉和LATV组肾和主动脉的表达均明显低于SHR对照组(P<0.01或P<0.05)；同时，用药2组血脂水平亦明显低于SHR对照组(P<0.01或 P<0.05)。结论： 阿托伐他汀可下调CYP4A1基因的表达，这可能是其降低血压的作用机制之一。     

一氧化氮合酶和一些神经递质（神经肽）在自发性高血压大鼠孤束核的分布

用ＮＡＤＰＨ－ｄｉａｐｈｏｒａｓｅ组织化学和免疫细胞化学方法，观察和比较了一氧化氮合酶、酪氨酸羟化酶、５－羟色胺、Ｐ物质和亮氨酸脑啡肽在自发性高血压大鼠和正常对照大鼠孤束核的分布。结果显示，孤束核内一氧化氮合酶阳性细胞在高血压组少于对照组，有显著性差异（Ｐ＜０．０５）。孤束核Ｐ物质和亮氨酸脑啡肽免疫阳性物在高血压组多于对照组；酪氨酸羟化酶免疫阳性物高血压组少于对照组；５－羟色胺免疫阳性物在两组的分布无明显差异。提示一氧化氮在孤束核是一种降压性局部神经调质，与其在心血管系统的降压作用一致。中枢Ｐ物质含量的异常增加可能是高血压发病的原因之一。孤束核脑啡肽含量的异常增加与高血压的形成有关，痛觉和高血压之间可能存在一些共同的发生机制。酪氨酸羟化酶在高血压组降低提示孤束核内酪氨酸羟化酶对维持正常血压发挥重要作用．孤束核内５－羟色胺与血压调节无关。     

Alterations in tissue concentration and gene expression of adrenomedullin in spontaneously hypertensive rats

In order to elucidate the role of adrenomedullin in hypertension, we have compared concentrations of immunoreactive rat adrenomedullin and adrenomedullin messenger RNA levels in tissues of 8-week-old spontaneously hypertensive rats (SHR) with those of age-matched Wistar-Kyoto rats (WKY). The adrenomedullin immunoreactivity concentrations in adrenal gland and cardiac atrium were significantly higher in SHR than in WKY. The adrenomedullin content of cardiac ventricle was also significantly higher in SHR than in WKY. The rat adrenomedullin messenger RNA levels in adrenal gland and heart of SHR were also higher than those of WKY. These results suggest that adrenomedullin participates in the mechanism to counteract the blood pressure elevation in SHR.