ERK表达及活化在自发性高血压大鼠心肌肥厚中作用的研究

目的以SHR大鼠作为自发性高血压动物模型,研究ERK表达及活化在高血压并发左心室肥厚(LVH)中的作用.方法 SHR大鼠按年龄分为8周、16周和24周三组,以Wistar大鼠作为对照.ERK表达及活性定量测定采用Western Blot方法.结果 SHR左室质量指数与磷酸化ERK水平正相关.24周龄SHR大鼠基础ERK 表达水平较8周龄和16周龄减少,亦明显低于同龄Wistar大鼠(P=0.003);SHR大鼠ERK活化程度高于同龄Wistar大鼠,随年龄增加,SHR磷酸化ERK表达量增加.结论 ERK的活化参与高血压心肌肥厚的发病.     

替米沙坦对高血压大鼠血管前纤维蛋白1及ERK磷酸化水平的影响

目的：探讨替米沙坦对自发性高血压大鼠（SHR）血管前纤维蛋白1（Profmn-1）及细胞外信号调节激酶（ERK1／2）磷酸化水平的影响。方法：选取10周龄SHR及其同源对照魏-凯氏（WKY）大鼠,给予替米沙坦（5～10mg／kg·d）或安慰剂,为期10周。尾套法测量大鼠尾血压。采用实时定量聚合酶链式反应（PCR）和Western免疫印迹检测治疗后大鼠主动脉组织中Profilin-1mRNA和蛋白及ERK1／2磷酸化水平。结果：与WKY对照组相比,SHR大鼠血压明显升高[（126±3．5）mmHg：（195±6．1）mmHg],伴血管Profilin—1mRNA[（1．0±0．11）;（7．8±0．57）]及ERK硫酸化水平[（1．0±0．11）：（2．43±0．19）]表达明显升高（P均〈0．01）,而经替米沙坦治疗后SHR大鼠血压明显降低[替米沙坦低剂量组（169±6．2）mmHg,高剂量组（161±4．9）mmHg],伴Profilin-1mRNA[替米沙坦低剂量组（4．45±0．92）,高剂量组（1．95±0．41）]表达及ERK1／2磷酸化水平[替米沙坦低剂量组（1．62±0．20）,高剂量组（1．34±0．09）]明显下调（P均〈0．05）。结论：长期替米沙坦治疗可降低高血压大鼠血压水平,降低血管Profilin-1表达及ERK1／2磷酸化水平,提示替米沙坦对高血压血管重塑具有一定的保护功效。     

自发性高血压大鼠左室重构中细胞增殖及心肌细胞DNA倍体的变化

目的 :探讨组织细胞增殖在高血压左室重构中的变化规律。方法 :不同年龄 (1周、3、6、12月龄 )的 WKY和 SHR大鼠 ,称重法测量左室肥厚指数 ,L SAB免疫组化法检测左室中增殖细胞核抗原 (PCNA)的蛋白表达 ,图像细胞分析技术原位检测心肌细胞核 DNA倍体和细胞核面积的变化。结果 :1周、3、6、12月龄各组 SHR左室肥厚指数分别比同龄WKY增加 18%、15 %、2 6 %、2 6 % ,均有统计意义。 1周龄和 3月龄 SHR心肌细胞 PCNA阳性率较同龄 WKY显著增加 ;而纤维细胞阳性率在两株大鼠无明显差异。 6月龄 WKY无阳性细胞表达 ,SHR心肌细胞阳性率为 0 .13± 0 .0 7,无统计学意义。 12月龄 WKY和 SHR均无阳性细胞表达。各年龄段SHR4倍体心肌细胞核百分比和心肌细胞核面积均较 WKY大鼠显著增加。在 1周至 12月龄时 ,两株大鼠 4倍体心肌细胞核比例均随年龄呈线性生长 ,6月龄后 WKY倍体比例相对稳定 ,SHR增加幅度明显下降。回归分析表明 ,成年 SHR4倍体比例与动脉收缩压呈相正关性。结论 :SHR左室重构在新生鼠即已发生 ,在 6月龄时基本完成 ,并且不完全依赖于血压的增高。这种病理性变化表现为心肌细胞的增殖 (肥大和 /或增生 ) ,而纤维细胞无明显增殖     

缬沙坦对自发性高血压大鼠心肌凋亡及bcl-2、bax蛋白的表达的影响

目的　探讨自发性高血压大鼠 (SHR) ,左心室肥厚过程中 ,心肌组织凋亡情况及凋亡调节蛋白bcl 2、bax表达的变化 ,AT1受体拮抗剂缬沙坦对心肌细胞凋亡的影响。方法　实验动物为 8周龄分为缬沙坦治疗组和非治疗组(SHR无药组 ) ,以Wistar鼠作为正常血压对照组 ,观察期限为 8周。采用TdT介导的dUTP缺口末端标记技术(TUNEL)判定心肌细胞凋亡 ,并行免疫组化、Western印迹等方法检测实验动物心肌组织凋亡调节蛋白bcl- 2、bax的表达情况。结果　SHR心肌组织中存在细胞凋亡现象 ,并有bax高表达。缬沙坦治疗 8周后 ,SHR心肌组织bax蛋白表达显著降低至接近Wistar组。Bcl 2蛋白在SHR治疗组及Wistar组表达较SHR非治疗组有增高趋势 (P >0 0 5 )。前两组bax/bcl 2比值较后者显著降低 (P <0 0 5 )。结论　心肌细胞凋亡是代偿性心肌肥厚可能机制之一。高血压病早期缬沙坦在降压同时可有效抑制心肌细胞凋亡 ,具有积极的抗心室重建作用。     

桑杞清眩颗粒干预自发性高血压大鼠心肌细胞凋亡的实验研究

目的观察桑杞清眩颗粒对高血压心肌重构的抑制作用及其可能机制。方法选8只4周龄雄性WKY大鼠和16只4周龄雄性自发性高血压(SHR)大鼠,WKY大鼠作为对照组(WKY),SHR大鼠随机分为模型组(SHR组)和给药组(SQ+SHR组),每组8只。每组在治疗16周后处死大鼠,尾套法测量SHR尾动脉收缩压、舒张压、平均压,计算心脏重量指数;用脱氧核苷酸末端转移酶介导的缺口末端标记法(TUNEL)染色来检测凋亡心肌细胞;用蛋白免疫印迹法检测大鼠心肌组织中B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、活化型半胱天冬酶-3(cleaved Caspase-3)。结果与WKY组相比,桑杞清眩颗粒显著抑制SHR大鼠收缩压的升高、心脏重量指数的增加、抑制高血压引起的大鼠心肌细胞凋亡、Bcl-2的降低及Bax和cleaved Caspase-3的增加。结论桑杞清眩颗粒可以抑制SHR大鼠血压升高,减轻心肌肥厚,其作用机制可能与抑制自发性高血压大鼠心肌细胞凋亡有关。     

替米沙坦对自发性高血压大鼠心肌ACE2表达的影响

选择16只12周龄雄性自发性高血压大鼠随机分为自发性高血压组（SHR组,n=8）和替米沙坦组（n=8）,替米沙坦组大鼠予以替米沙坦5mg／（kg·d）灌胃,给药时间8周,同时取8只12周龄雄性Wistar大鼠作为对照组,利用免疫组织化学染色和逆转录聚合酶链反应检测各组动物心肌血管紧张素转换酶2（ACE2）的表达。结果发现,与对照组比较,SHR组心肌ACE2表达显著降低（P〈0．05）,与SHR组比较,替米沙坦组经8周治疗后,ACE2表达显著增高（P〈0．05）,替米沙坦组血压、心肌重量指数及心肌胶原容积分数较SHR组均明显下降（P均〈0．05）。认为高血压大鼠心肌ACE2表达降低,替米沙坦能够上调高血压大鼠心肌ACE2的表达,该作用可能为血管紧张素Ⅱ1型受体拮抗剂在高血压病心脏保护作用的新机制。     

肥厚心肌细胞钠通道电流

目的探讨自发高血压大鼠(SHR)肥厚心肌钠通道电流的动态演变规律及与左心室肥厚的关系。方法采用全细胞膜片钳技术记录10、24和34周龄SHR左心室心肌钠通道电流及膜电容,同时测定大鼠动脉收缩压和左心室质量指数,以10周龄Wistar大鼠为对照组。结果(1)SHR的左心室质量指数及膜电容明显大于Wistar大鼠(P<0.01)。在SHR中,各组大鼠的膜电容和左心室质量指数具有明显差别(P<0.01)。(2)10周龄和24周龄SHR肥厚心肌钠通道电流密度与10周龄Wistar大鼠比较无明显变化(P>0.05);34周龄SHR肥厚心肌钠通道电流密度>10周龄Wistar大鼠[(-18.3±1.9)pA/pFvs(-15.3±2.0)pA/pF,P<0.05)。(3)钠通道电流密度与左心室质量指数呈正相关关系(r=0.879,P<0.01)。结论左心室肥厚越明显,钠通道电流密度越升高。     

高血压大鼠心脏肥厚过程中心肌细胞凋亡心肌纤维化动态观察

目的 探讨SHR心脏肥厚进展阶段心肌细胞凋亡、心肌纤维化及左室重构特点及其相互关系。方法 分别采用末端脱氧核糖核苷酸转移酶介导dUTP缺口末端标记（TUNEL）、放射免疫测定及病理检查方法对16周、24周龄、32周龄SHR心肌细胞凋亡指数（APOI）、心肌胶原容积分数（VF）和心肌血管周围胶原面积（PVCA）、血浆和组织血管紧张素Ⅱ检测,并以同龄Wister大鼠作对照。结果 与同龄正常血压Wistar大鼠比较,SHR各周龄组收缩压明显增高、心脏肥厚指标心脏重量（HW）、左室重量（LVW）、左室重量指数（LVW/BW) 显著增加;各周龄组SHR心肌细胞APOI显著增加,各周龄组间无显著性差异;各周龄组SHR大鼠血浆、心肌组织Ang Ⅱ明显增高;24、32周龄SHR的CVF和PVCA显著增加;SHR心肌组织Ang Ⅱ分别与APOI、CVF呈显著正相关,APOI与CVF呈显著正相关。结论 心肌细胞凋亡与心肌纤维化参与SHR代偿性心脏肥厚阶段心脏重构病理过程,组织Ang Ⅱ是导致SHR代偿性心脏肥厚阶段心肌细胞凋亡与心肌纤维化的重要机制之一。     

高血压大鼠心脏肥厚过程中心肌细胞凋亡心肌纤维化动态观察

目的探讨SHR心脏肥厚进展阶段心肌细胞凋亡、心肌纤维化及左室重构特点及其相互关系.方法分别采用末端脱氧核糖核苷酸转移酶介导dUTP缺口末端标记(TUNEL)、放射免疫测定及病理检查方法对16周龄、24周龄、32周龄SHR心肌细胞凋亡指数(APOI)、心肌胶原容积分数(CVF)和心肌血管周围胶原面积(PVCA)、血浆和组织血管紧张素Ⅱ检测,并以同龄Wister大鼠作对照.结果与同龄正常血压Wistar大鼠比较,SHR各周龄组收缩压明显增高、心脏肥厚指标心脏重量(HW)、左室重量(LVW)、左室重量指数(LVW/BW)均显著增加;各周龄组SHR心肌细胞APOI显著增加,各周龄组间无显著性差异;各周龄组SHR大鼠血浆、心肌组织AngⅡ明显增高;24、32周龄SHR的CVF和PVCA显著增加;SHR心肌组织AngⅡ分别与APOI、CVF呈显著正相关,APOI与CVF呈显著正相关.结论心肌细胞凋亡与心肌纤维化参与SHR代偿性心脏肥厚阶段心脏重构病理过程,组织AngⅡ是导致SHR代偿性心脏肥厚阶段心肌细胞凋亡与心肌纤维化的重要机制之一.     

CTGF和ICAM-1在自发性高血压大鼠肾脏的表达及意义

目的 研究结缔组织生长因子(connective tissue growth factor,CTGF)和可溶性细胞间黏附分子(intercellular adhesion molecule-1,ICAM-1)在自发性高血压大鼠(spontaneously hypertensive rat,SHR)肾脏中的表达及其与高血压肾损害的关系. 方法 以雄性Wistar-Kyoto (WKY)大鼠和SHR为研究对象,测量12周和32周时尾动脉压、肾功能和尿β2-微球蛋白(β2-microglobulin, β2-MG),用免疫组织化学法检测CTGF和ICAM-1在肾脏中的表达,并在光镜下观察各组大鼠肾组织形态学改变. 结果 与同龄WKY大鼠比较,12周和32周时SHR的尿素氮和血肌酐的差异无统计学意义,而尾动脉压和β2-MG明显增高(P＜0.01或P＜0.05).且在SHR组,32周龄大鼠的尿β2-MG也比12 周龄大鼠明显增加(P＜0.05).免疫组织化学半定量检测发现,SHR组肾脏中CTGF和ICAM-1的表达较同龄WKY大鼠明显升高(P＜0.05或P＜0.01).同样在SHR组,CTGF和ICAM-1在32 周龄大鼠肾脏的表达也比12周龄显著增加(P＜0.05),而且CTGF和ICAM-1的表达与尿β2-MG有显著正相关关系(P＜0.05). 结论 CTGF和ICAM-1在SHR肾脏表达的显著增加,可能是慢性高血压导致的肾损害的重要机制之一.     

自发性高血压大鼠心肌fas基因表达与左室肥厚关系探讨

目的 探讨自发性高血压大鼠（SHR）心肌fas表达及其与左室肥厚的关系。方法 自发性高血压大鼠（SHR）与正常血压大鼠各16号，尾套法测收缩压，逆转录-聚合酶边反应（RT-PCR）法测心肌fas mRNA表达。结果 与WKY相比，SHR心肌fas表达、左室重量指数(LVMI)均显著升高，且二者呈正相关。结论 自发性高血压大鼠早期心肌肥厚时心肌fas表达已经升高，可能参与后期心衰的发生。     

Effect of ubiquinone on contractile function and antioxidant status of the myocardium in spontaneously hypertensive rats

During the period of aging of spontaneously hypertensive rats (SHR) between 6 and 13 weeks the systolic arterial pressure increased from 131+/-2 up to 176+/-3 mm Hg while in the control group of WKY rats it reached 122+/-2 mmHg. The hypertension was combined with myocardial hypertrophy -- the relative weight of SHR heart was 24% higher. The contractile myocardial function of the isolated isovolumic heart of SHR group did not differ from WKY group in a wide range of coronary perfusion rates. During oxidative stress induced by 40-min intracoronary introduction of H(2)O(2) function of hypertrophied SHR hearts fell significantly deeper. This coincided with decreased myocardial activity of superoxide dismutase and glutathione peroxidase by 29-30%, and increased catalase activity by 18%. The rate of generation of active forms of oxygen (hydroxyl radicals HO(.-)) in mitochondria from SHR hearts was higher as compared with WKY. Thus, the development of hypertension was combined with decreased antioxidant protection of the myocardium. The addition of ubiquinone to drinking water (approximately 10 mg/kg/day) for 6 weeks did not affect arterial pressure level, but was associated with two times lesser degree of myocardial hypertrophy. The hearts of SHR that received ubiquinone differed from those not treated with ubiquinone by increased maximal level of myocardial contractile function, and by improved myocardial relaxability and distensibility. After administration of H(2)O(2), myocardial function of SHR was kept on higher level. That was combined with less myocardial oedema, better preservation of antioxidant enzymes and reduced rate of succinate-dependent generation of superoxide radicals in mitochondria from hearts of ubiquinone treated SHR. The results have shown, that administration of ubiquinone to rats with hereditary hypertension reduces degree of myocardial hypertrophy, improves functional properties of the myocardium, promotes effective protection of antioxidant enzymes and increases the resistance of the cardiac muscle to oxidative stress.     

阿托伐他汀对自发性高血压大鼠心肌组织p21表达的影响及其意义

目的:观察阿托伐他汀(ATV)对自发性高血压大鼠(SHR)心肌组织中p21表达的影响,探讨其改善心肌肥厚的可能机制。方法:将16只8周龄SHR随机分为2组(n=8):ATV药物干预组(ATV组)与SHR模型对照组(SHR组),并以8只同周龄Wistar-Kyoto大鼠作为正常对照组(WKY组)。ATV组用ATV 50 mg/(kg·d)灌胃,SHR组与WKY组采用等容量蒸馏水每日同时灌胃。每隔2周测1次血压。10周后,观察大鼠血脂、心肌肥厚指标、p21 mRNA及其蛋白表达的改变。结果:干预10周后,ATV组及SHR组血脂、血压无明显差异。ATV组左室质量指数低于SHR组(P<0.01)。ATV组p21mRNA及蛋白的表达明显高于SHR组(P<0.01)。心肌组织p21mRNA的表达与全心质量与体质量比(HW/BW)呈负相关(r=-0.709,P<0.01),与左室质量与体质量比(LVW/BW)呈负相关(r=-0.665,P<0.01)。结论:ATV可上调SHR肥厚心肌组织中p21的表达,可有效改善左室肥厚。     

Abnormal polyamine metabolism in hypertensive cardiac hypertrophy

In order to assess myocardial hypertrophic activity during the process of hypertensive cardiac hypertrophy in the presence and absence of treatment with anti-hypertensive agents, we analyzed myocardial polyamine concentrations in spontaneous hypertensive (SHR) rats and control rats of Wistar Kyoto (WKY) strain. The anti-hypertensive agents studied were diltiazem, hydralazine and captopril, each of which was administered for 5 weeks. In comparison with WKY rats, SHR rats showed elevated blood pressure and enlarged hearts with higher myocardial spermidine concentration. Although blood pressure was lowered in the diltiazem-treated SHR rats, heart weight and myocardial spermidine concentration increased as in untreated SHR rats. In the hydralazine-treated group increases in both blood pressure and myocardial spermidine concentration were suppressed, while an increase in heart weight was not. In the captopril-treated group, increases in blood pressure, heart weight and spermidine concentration were all suppressed. Since spermidine level appears to be a sensitive indicator of hypertrophic activity in the heart, this study suggests that captopril exerts an inhibitory effect on hypertensive cardiac hypertrophy whereas diltiazem does not. It also suggests that hypertrophy may reach a certain plateau level earlier in the hydralazine-treated animals than in others.     

Characterization of myocardial hypertrophy in prehypertensive spontaneously hypertensive rats: interaction between adrenergic and nitrosative pathways

OBJECTIVE AND METHODS: Left ventricular hypertrophy in human and experimental hypertension is not always associated with pressure overload but seems to precede an increase in blood pressure. In this study, performed in male 5-week-old prehypertensive spontaneously hypertensive rats (SHR; n = 65) and age-matched Wistar-Kyoto rats (n = 56), the relationship between myocardial structure and activation of the adrenergic and nitric oxide systems was evaluated. RESULTS: Body weight, blood pressure and heart rate were similar in both groups. A higher left ventricle/body weight ratio was found in SHR, as a result of greater mononuclear (+47%) and binuclear (+43%) myocyte volumes, without changes in interstitial collagen. Both adrenergic and nitric oxide pathways were activated in SHR, as expressed by higher myocardial norepinephrine content, tyrosine hydroxylase activity, myocardial nitric oxide synthase 3 expression and protein nitration, indicating greater peroxynitrite (ONOO) generation from nitric oxide and superoxide. No difference was measured in nitric oxide synthase 1 expression, whereas nitric oxide synthase 2 was undetectable. A positive correlation between myocardial tyrosine hydroxylase activity and protein nitration was observed in SHR (r = 0.328; P < 0.01). Early treatment with a superoxide dismutase mimetic, 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl, from the third to the fifth week of age, reduced ONOO generation, protein nitration and sympathetic activation in SHR without changes in myocardial structure. CONCLUSION: In prehypertensive SHR, left ventricular hypertrophy is associated with adrenergic and nitrosative imbalance. Early superoxide dismutase mimetic treatment in SHR effectively reduces higher myocardial ONOO generation, sympathetic activation, and heart rate without affecting the development of myocardial hypertrophy.     

肝细胞生长因子与自发性高血压大鼠心肌纤维化的相关研究

目的 探讨高血压进展过程中肝细胞生长因子(hepatocyte growth facor,HGF)表达与心肌纤维化的关系及血管紧张素Ⅱ受体1(ATl)拮抗剂洛沙坦的干预作用. 方法 以不同周龄自发性高血压大鼠(SHR)为心肌纤维化模型,WKY(Wistar-Kyoto)大鼠为对照组.用洛沙坦对SHR大鼠进行治疗.各周龄组WKY、SHR大鼠及干预后的SHR大鼠处死后取心脏制成石蜡切片,利用麦松三色法检测心肌胶原,免疫组织化学方法检测心肌组织HGF,Leica Qwin彩色图像分析系统分析图片. 结果 SHR大鼠心肌胶原容积(collagen volume fraction,CVF)随周龄增长而增加,8、12、16、24和32周分别为(1.8±0.1)%、(1.8±0.1)0A、(3.8±0.4)%、(7.3±0.4)%和(13.4±1.8)%,与心肌组织HGF含量呈负相关(r=-0.8820,P<0.05).洛沙坦十预可增加HGF表达,降低CVF.结论 高血压心肌纤维化可能与心肌组织HGF抗纤维化作用降低有关,AT<,1>拮抗剂治疗可以增加心肌组织HGF表达从而改善心肌纤维化.     

自发性高血压大鼠肥厚左心室的蛋白质组学研究

目的心肌肥厚是高血压患者心血管事件发生和死亡的主要危险因素,其机制仍未完全阐明。应用双向凝胶电泳/质谱的经典蛋白质组学方法,比较不同年龄自发性高血压大鼠(SHR)肥厚心肌的蛋白质表达谱的差异。方法取4周、20周龄雄性 SHR 和 WKY 大鼠,观察血压和心肌肥厚情况;抽提其左心室组织蛋白,经二维凝胶电泳(2-DE)分离蛋白,银染后计算机图象分析寻找蛋白表达差异点,并以基质辅助激光解吸电离-飞行时间-飞行时间质谱测量法(MALDI-TOF-TOF MS)分析鉴定蛋白。结果 SHR 在血压末升高时就已存在心肌肥厚。经二维胶图比较共找出27个差异蛋白点,质谱分析鉴定出20个差异蛋白,涉及能量代谢、线粒体氧化磷酸化和氧化应激反应等。其中13个蛋白的变化发生在4周龄 SHR 血压未升高时;另7个蛋白表达变化发生于20周龄血压持续升高状态下的 SHR 肥厚心肌中。结论 SHR 肥厚心肌中脂肪酸氧化和葡萄糖有氧氧化中的酶下调,而糖酵解的关键酶明显上调,且这些变化大多发生在血压升高前;线粒体氧化磷酸化的多种酶和一些参与抗氧化作用的蛋白均发生了变化,提示在 SHR 的心肌肥厚过程中物质能量代谢和氧化应激也具有重要作用。     

Changes in Creatine Kinase Expression Induced by Exercise in Borderline Hypertensive Rat Hearts

Hypertrophy in hypertensive hearts is associated with increased risk of cardiac morbidity and mortality that is not characteristic of exercised hearts. This study was done to determine whether exercise training of normotensive and borderline hypertensive rats induces the increased myocardial expression of BB and MB isoforms of creatine kinase (CK) that characterizes hypertensive hypertrophy. Spontaneously hypertensive (SHR), borderline hypertensive (BHR), and normotensive Wistar-Kyoto (WKY) rats were subjected to either an 8% sodium chloride diet or swim training to produce myocardial hypertrophy. Both exercise and a high salt diet induced an increase in the combined expression of CK-MB and CK-BB in SHR after 2 months. However, since swimming also exacerbated hypertension in SHR, exercise induced effects on CK were not distinguishable from those of hypertension. In WKY, neither exercise nor a high salt diet induced significant changes in CK isozyme expression. In BHR fed a high sodium chloride diet, significant increases in mean arterial pressure and left ventricular weight to body weight were not associated with changes in CK expression. In contrast, following 10 months of swim training BHR exhibited mild hypertrophy, decreased resting heart rates, and an increase in the combined expression of CK-MB and CK-BB. Therefore, exercise associated with a cardiac training effect in BHR induced changes in CK isozyme expression similar to those in hypertensive hearts.     

Changes in myocardial collagen in spontaneously hypertensive rats (SHR)]

The aim of this study was to evaluate whether left ventricular hypertrophy in spontaneously hypertensive rats (SHR) is accompanied by myocardial collagen quantitative and/or qualitative changes. 15 SHR and 20 control normotensive rats (WKR) of three months of age were used. At this age, hypertension has already caused a significant increase in the ratio of the ventricular mass to body weight (mg/g) in hypertensive animals (SHR: 5.11 +/- 0.21; WKR: 3.40 +/- 0.22; p less than 0.001). With respect to body mass, the amount of collagen elicited from the hydroxyproline concentration increases in SHR but remains percentually the same with respect to the biventricular mass. In SHR, changes in the amount of type-1 alpha chains and type-V alpha chains, and the presence of a low molecular weight collagenous fraction have been observed. Moreover, we have found an increase in the ratio of type-1 alpha 1 chains to type-1 alpha 2 chains. This change might be related to the appearance of a type-1 alpha 1 trymer. The presence of such a type-1 alpha trymer and of low molecular weight collagenous fractions may suggest the appearance of fetal collagenous isoforms in ventricular myocardium, due to the increased pressure load as well as to the increased turnover (an index of a remodelling activity of cardiac stroma). These changes might play a role in the transformation of myocardial viscoelastic properties in SHR with a progressive diastolic stiffness of the ventricular wall.     

Some enzyme characteristics of spontaneously hypertensive rats myocardium

In order to ascertain the pathogenesis of myocardial cell vulnerability in spontaneously hypertensive rats (SHR), several enzyme activities were examined by using subcellular fractions of myocardium and compared to those in Wistar-Kyoto rats (WKY). In the normotensive WKY heart, both 5'-nucleotidase and Na+/K(+)-ATPase, which are plasma membrane associated enzymes, increased with age. But in the SHR heart, both enzymes were lower at 16 weeks than they were at 10 weeks of age. Moreover, at 16 weeks of age they were lower in SHR than in WKY. On the other hand, NADP(+)-isocitrate dehydrogenase activity, a mitochondria associated enzyme, was higher in SHR than in WKY at 6 weeks, but lower at 10 and again at 16 weeks of age. The activities of both acid phosphatase and N-acetyl-beta-glucosaminidase, which are lysosomal enzymes, decreased with age in SHR but not in WKY. These results suggest that an enzymatic alteration in the plasma membrane and mitochondria may be one of important factors behind myocardial vulnerability in the SHR heart.