冷应激高血压大鼠血管舒缩功能的研究

目的　探讨寒冷环境因素在大鼠高血压发病中的作用。方法　 40只 3月龄雄性Wistar大鼠 ,随机分成寒冷组和对照组 ,寒冷组动物置于 4± 2℃的冷环境中 ,每天 4小时 ,共 8周。每周测鼠尾血压、心率、体重。 8周后取胸主动脉完整血管环 ,生理多导记录仪分析血管活性物质对离体血管环舒缩功能的影响。结果　寒冷组的鼠尾压、心率均明显升高 (P <0 0 1 ) ,四周鼠尾血压达到最高 (为 1 36 .4± 5 .5mmHg)。血管环功能实验表明 ,冷应激组大鼠血管环对AngⅡ、NE、NTG的反应性与正常组无差别 ,但对钙通道开放剂 (Bayk 8644)的收缩反应明显增强 (P <0 0 1 )及Ach引起的内皮依赖的舒张反应明显减弱 (P <0 0 5)。结论　冷应激环境因素刺激可导致大鼠高血压和血管功能异常 ,其机制可能与钙通道异常开放和内皮依赖的舒张功能受损有关     

软脉灵对自发性高血压大鼠心肌纤维化的作用

目的 观察软脉灵对自发性高血压大鼠(SHR)心肌纤维化的影响.方法 选择12周龄雄性SHR 36只,随机分为4组,软脉灵大剂量和小剂量组、空白组、阳性对照组.血压正常的京都Wistar大鼠(WKY)为正常对照组(WKY组).治疗前及治疗12周后用尾袖法测定动脉血压,称重后处死,取心脏,计算左心室重量与体重比(LVM/BW),天狼星红染色,计算心肌胶原容积分数.结果 软脉灵大剂量、小剂量组治疗12周后,收缩压(SBP)均显著低于空白组(P<0.01).与空白组相比,软脉灵大剂量组对SHR心肌外斜层纤维化有明显抑制作用(P<0.01),而软脉灵小剂量组则无影响;与空白组相比,软脉灵大剂量和小剂量组对SHR心肌中环层纤维化及心肌血管周围纤维化均有明显抑制作用(P<0.01).结论 软脉灵可以抑制SHR血压的发展,抑制SHR的心肌纤维化.     

冬虫夏草对肾性高血压大鼠心血管功能的影响

目的观察青海产冬虫夏草对肾性高血压大鼠血压、心肌肥大、心血管功能的影响.方法将体重160 g～180 g健康雄性Wistar大鼠随机分为3组:对照组、高血压纽及治疗组.于术后第10天,大鼠灌胃冬虫夏草煎剂2 mL,每天2次连续20 d,观察冬虫夏草对大鼠血压、心肌肥大、心血管功能的影响.结果冬虫夏草明显降低肾性高血压大鼠血压,改善高血压大鼠的心肌肥大及血管重构.结论冬虫夏草对肾性高血压有治疗作用.     

脑心通对自发性高血压大鼠心肌纤维化的影响

目的观察脑心通对自发性高血压(SHR)大鼠心肌纤维化的影响。方法选择12周龄雄性SHR大鼠(二级)32只,随机分成4组,脑心通大剂量组予脑心通1.5g/(kg.d),脑心通小剂量组予脑心通0.5g/(kg.d),氯沙坦组予氯沙坦30mg/(kg.d),SHR组每日灌等量蒸馏水。另设周龄、性别相匹配的WistarKyoto(WKY)大鼠8只(WKY组)。治疗12周后用尾袖法测定动脉血压,称重后处死。计算左心室重量与体重比(LVM/BW)。天狼星红染色,计算机图像分析计算心肌胶原容积分数。结果脑心通大、小剂量组治疗后SBP均显著低于SHR组(P<0.01)。脑心通大剂量组SHR治疗后SBP较治疗前明显降低(P<0.01),而小剂量组治疗前后SBP比较无统计学意义。脑心通大、小剂量组SHR心肌胶原纤维含量显著低于SHR组(P<0.01)。结论脑心通可以抑制SHR大鼠的心肌纤维化,改善高血压所致的心肌重塑。     

氯沙坦或卡托普利对自发性高血压大鼠心脏纤维化的干预研究

目的　探讨在不同水平阻断肾素 -血管紧张素系统 (RAS)对高血压心肌纤维化的影响。方法　 2 9只自发性高血压大鼠 (SHR)随机分成 (1)SHR对照组 (n =15 ) ;(2 )氯沙坦组 (n =7,30mg·kg-1·d-1) ;(3)卡托普利组 (n =7,10 0mg·kg-1·d-1) ;(4)WKY(n =12 )为非高血压组。治疗组每日灌胃给药 ,对照组蒸馏水灌胃 15周后 ,获取标本。结果　 1.SHR心肌血管紧张素Ⅱ (AngⅡ )和醛固酮 (Ald)浓度、羟脯氨酸和Ⅰ /Ⅲ型胶原比值较同龄WKY大鼠明显增高 (P <0 0 1) ,而心肌胶原单体 /二聚体 (α/ β)比值和基质金属蛋白酶 - 1(MMPs- 1)活力降低 (P <0 0 1) ,且随病程而进一步升高或降低。 2 .经氯沙坦或卡托普利干预后 ,心肌AngⅡ、Ald浓度、心肌羟脯氨酸和Ⅰ、Ⅲ型胶原比值有不同程度的降低 (P <0 0 1) ,而心肌胶原单体 /二聚体 (α/ β)比值和MMPs- 1活性升高 (P <0 0 1) ,逆转了心肌纤维化。3.氯沙坦在改善胶原表型、胶原可溶性及提高MMPs- 1活性优于卡托普利。结论　不同水平阻断肾素血管紧张素系统对纤维化逆转不仅减少胶原含量 ,还改善表型和交联的异常     

钙对自发性高血压大鼠肠系膜血管床膜的稳定作用

目的研究钙对ＳＨＲ肠系膜血管床的膜稳定作用。方法分离麻醉鼠肠系膜血管进行灌流。以灌流压的变化作为其舒缩活动的指标。结果（１）１０ｍｍｏｌ／Ｌ钙可使ＮＥ引起的收缩出现舒张，ＳＨＲ的舒张比ＷＫＹ弱１５．８３％（Ｐ＜０．０５）。（２）在ＫＣｌ收缩的基础上４０ｍｍｏｌ／Ｌ钙也引起血管床的舒张，ＳＨＲ比ＷＫＹ舒张弱１５．０７％（Ｐ＜０．０５）。（３）在无钾及无钙溶液中（不含ＥＧＴＡ）孵育的标本加钙（３．５ｍｍｏｌ／Ｌ）时，ＳＨＲ的反应明显高于ＷＫＹ鼠，但应用ＥＧＴＡ后再重复前次实验，则两者的反应差别消失。结论钙对肠系膜血管床平滑肌有膜稳定作用，ＳＨＲ较ＷＫＹ的此种钙的膜稳定作用减弱。     

通心络治疗对自发性高血压大鼠心肌纤维化的影响

目的：观察通心络对自发性高血压大鼠(SHR)心肌纤维化的影响。方法：30只12周龄雄性SHR大鼠，随机分成大剂量通心络组、小剂量通心络组、SHR空白对照组3组，每组10只；另取10只同龄雄性正常血压WKY大鼠作为对照组。给药12周，天狼星红染色法使肢原特殊染色，计算机图像分析测量心肌切片的肢原容积分数和心肌小动脉周围肢原面积与小动脉面积比表示心肌纤维化程度；放免法(RIA)测定血浆AngⅡ的浓度：结果：与SHR组相比，大、小剂量通心络组均能在一定程度上抑制S服血压升高(P＜0．05)。通心络大、小剂量组治疗均能在一定程度上改善SHR大鼠左心室肥厚(P＜0．05)，并使心室内、外膜及心肌小动脉周围的胶原减少，同时血浆AngⅡ浓度较SHR组下降，其中大剂量组各指标均较SHR有统计学意义(P＜0．05)。结论：通心络对SHR大鼠的心肌纤维化有显著的抑制作用。     

血管内皮生长因子与自发性高血压大鼠血管重构的关系

目的探讨血管内皮生长因子与血管重构的关系。方法12只13周龄雄性自发性高血压大鼠(SHR组)作为观察组,12只同周龄雄性WKY大鼠作为正常血压对照组(WKY组)。分别于实验的第4、8周末每组处死大鼠各6只。采用酶联免疫吸附法测定血浆血管内皮生长因子浓度;放射免疫法测定颈动脉血管紧张素Ⅱ浓度;病理图象管理系统测定颈动脉管腔横截面积、内弹力层围绕面积、外弹力层围绕面积,评价内膜和中膜增生程度;免疫组织化学法检测颈动脉血管内皮生长因子蛋白表达。结果与WKY组比较,SHR组血浆血管内皮生长因子浓度明显下降,颈动脉血管内皮生长因子蛋白表达明显减弱,颈动脉血管紧张素Ⅱ浓度却显著升高(P<0.01),8周末这一作用更加显著(P<0.01);SHR组内膜增生较WKY组明显,中膜面积显著增大(P<0.01)。结论在血管重构过程中,血管内皮生长因子水平下降,提示血管内皮生长因子可能具有改善血管重构的作用。     

Early,Short-Term Treatment with Captopril Permanently Attenuates Cardiovascular Changes in Spontaneously Hypertensive Rats

The purpose of the current study was to determine if early, short-term treatment of spontaneously hypertensive rats (SHR) with captopril would cause a persistent attenuation of the structural alterations of the heart, aorta, and coronary arteries that are commonly seen in adult SHR. Therefore, mating pairs of SHR were treated with captopril and the pups were kept on captopril (SHRC) or were taken off captopril at two months (SHROC). Untreated SHR and Wistar-Kyoto (WKY) rats were mated and served as controls. At 8–10 months of age, heart weight and left ventricular weight/body weight ratios were increased in SHR compared to WKY, SHRC, and SHROC. Aortic medial areas of SHR and SHROC were similar and were larger than WKY and SHRC. Nuclear density in SHR and SHROC was less than WKY and SHRC suggesting hypertrophy of the medial wall. In coronary vessels, medial thickness was greatest in SHR, while there was no difference among WKY, SHRC, SHROC. These data suggest that early, short-term treatment of SHR with captopril permanently attenuated the structural alterations in the heart and coronary vessels that are commonly seen in adult SHR.     

红细胞抗高血压因子对自发性高血压大鼠血管平滑肌细胞游离钙浓度的影响

观察从人红细胞中提取的抗高血压因子（ＡＨＦ）对自发性高血压大鼠（ＳＨＲ）和正常血压ＷＫＹ大鼠培养的主动脉平滑肌细胞胞内游离Ｃａ２＋浓度（［Ｃａ２＋］ｉ）的影响。结果ＳＨＲ和ＷＫＹ大鼠静息［Ｃａ２＋］ｉ无显著差别。ＫＣｌ（６０ｍｍｏｌ／Ｌ）对ＳＨＲ的激活显著大于ＷＫＹ大鼠，ＡＨＦ（１０－４ｇ／ｍｌ）可明显抑制由高钾诱导的［Ｃａ２＋］ｉ升高，对ＳＨＲ的抑制程度明显高于ＷＫＹ大鼠；去甲肾上腺素（ＮＥ，０．１ｍｍｏｌ／Ｌ）对两种大鼠的激活程度无显著差异。ＡＨＦ（１０－４ｇ／ｍＬ）也可明显抑制由ＮＥ（０．１ｍｍｏｌ／Ｌ）所诱导的ＶＳＭＣ［Ｃａ２＋］ｉ升高，对两种大鼠的抑制程度无显著差异。结论ＡＨＦ的降压作用可能与抑制细胞内［Ｃａ２＋］ｉ升高有关。     

Hypotensive Effect of Chamaemelum Nobile Aqueous Extract in Spontaneously Hypertensive Rats

This study aims to evaluate the hypotensive effect of Chamaemelum nobile aqueous extract (CNAE) in spontaneously hypertensive rats (SHRs). Single oral administration of CNAE (140 mg/kg) produced a significant reduction (p < 0.05) in systolic blood pressure (SBP) after 24 h of the administration. Daily oral administration of CNAE (140 mg/kg) during 3 weeks produced a significant reduction in SBP in the day 8 (p < 0.01) of treatment. Furthermore, CNAE produced a significant increase in urinary output and electrolytes excretion (p < 0.01) from the day 8 to the end of treatment. We conclude that CNAE possesses a hypotensive and diuretic effect in SHR.     

Role of Heme Oxygenase in Modulating Endothelial Function in Mesenteric Small Resistance Arteries of Spontaneously Hypertensive Rats

It has been proposed that endothelial dysfunction is due to the excessive degradation of nitric oxide (NO) by oxidative stress. The enzyme heme-oxygenase (HO) seems to exert a protective effect on oxidative stress in the vasculature, both in animal models and in humans. The objective of this study is to evaluate the effects of inhibition or activation of HO on endothelial function in mesenteric small resistance arteries of spontaneously hypertensive rats (SHR). Six SHR were treated with cobalt protoporphyrin IX 50 mg/Kg (CoPP), an activator of HO; six SHR with stannous mesoporphyrin 30 mg/Kg (SnMP), an inhibitor of HO, and six SHR with saline. As controls, six Wistar-Kyoto rats (WKY) were treated with CoPP, six WKY with SnMP, and six WKY with saline. Drugs were injected in the peritoneum once a week for 2 weeks. Systolic blood pressure (SBP) was measured (tail cuff method) before and after treatment. Mesenteric small resistance arteries were mounted on a micromyograph. Endothelial function was evaluated as a cumulative concentration-response curve to acetylcholine (ACH), before and after preincubation with N(G)-methyl-L-arginine (L-NMMA, inhibitor of NO synthase), and to bradykinin (BK). In SHR treatment with CoPP, improved ACH-and BK-induced vasodilatation (ANOVA p < 0.001) and this improvement was abolished by L-NMMA (ANOVA p < 0.001). SnMP was devoid of effects on endothelial function. In WKY, both activation and inhibition of HO did not substantially affect endothelium-mediated vasodilatation. The stimulation of HO seems to induce an improvement of endothelial dysfunction in SHR by possibly reducing oxidative stress and increasing NO availability.     

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.     

自发性高血压大鼠左室肥厚及心肌纤维化的动态变化

目的 生高血压大鼠（ＳＨＲ）血压增高的初期。增高期和稳定期左室肥厚和心肌纤维化参数的改变,探讨高血压左室肥厚和心肌纤维化的动态演化规律。方法 应用生化测定、病一检查结合计算机分析等方法,检测ＳＨＲ及其照ＷＫＹ在６周、１４周和２４周的收缩压、左室重量及左室重量指数、心肌细胞面积及横径、民胶原只分数（ＣＶＦ）、血管周围胶原面积（ＰＶＣＡ）及心肌组织内羟脯氨酸浓度。结果ＳＨＲ左室重量及左室重量指数、心肌     

Improvement of Vascular Remodeling in Spontaneous Hypertensive Rats with Traditional Chinese Medicine

Qin-Dan-Jiang-Ya-Tang (QDJYT) is a traditional Chinese herbal medicine for the treatment of hypertension. The effect of QDJYT on blood pressure (BP) and vascular remodeling in hypertension was investigated in the model of spontaneous hypertensive rats (SHR). Sixteen SHRs were divided into two groups: the SHR group and the SHR+ QDJYT group. Eight Wistar-Kyoto (WKY) rats were in the normal control group. QDJYT (750mg/kg) was orally administered daily for 12 weeks to the SHR+QDJYT group. After 12 weeks, thoracic aortas were segregated. The media thickness (MT) and the lumen diameter (LD) of the aortic wall, the ratios of MT to LD, the expression of basic fibroblast growth factor (bFGF) mRNA, and the level of its proteinic production were examined by histology, real-time PCR, and Western blot analysis, respectively. It was observed in our study that MT, MT/LD, the expression of bFGF mRNA, and the level of its proteinic production in aortic walls were higher in SHRs than in WKY rats. However, in the SHRs treated with QDJYT, we found MT, MT/LD, the expression of bFGF mRNA and the level of its proteinic production were lower than SHRs. These results suggest that QDJYT can improve the vascular remodeling in SHRs, and the mechanisms may be related to the suppressive effect of QDJYT on bFGF mRNA and its proteic productions in the aortic walls of SHRs.     

Carvedilol,A Novel Cardiovascular Agent,Inhibits Development of Vascular and Ventricular Hypertrophy in Spontaneously Hypertensive Rats

The effects of carvedilol, a novel cardiovascular agent, were evaluated in developing spontaneously hypertensive rats (SHR) for effects on hemodynamics, and the ability to effect the development of left ventricular, and vascular hypertrophy associated with chronic hypertension. Chronic oral administration of low dose carvedilol (20 mg/kg/day) was initiated when rats were 5 weeks of age, and experiments progressed until 14 weeks of age. Carvedilol-treated SHR had significantly reduced systolic blood pressures and heart rates throughout the duration of the experiment, and had significantly reduced ventricle/body weights by approximately 9.0%. Morphologic analysis of tertiary branches of the mesenteric artery revealed that carvedilol-treated     

The Role of Calmodulin in Neurotransmitter Release and Vascular Responsiveness in Spontaneously Hypertensive Rats

ABSTRACT

This study was designed to investigate the role of calmodulin in adrenergic transmission in hypertension. In perfused mesenteric vasculature: from spontaneously hypertensive rats(SHR, 7-9 weeks of age) and age-matched Wistar Kyoto rats(WKY), the effects of a specific calmodulin antagonist(W-7) on norepinephrine overflow and vascular responsiveness to endogenous and exogenous norepinephrine were examined.

The vasoconstrictor responses to electrical nerve stimulation and exogenous norepinephrine as well as norepinephrine overflow during electrical nerve stimulation were significantly enhanced in SHR compared with those in age-matched WKY. The calmodulin antagonist, W-7, reduced not only vasoconstrictor responses but also norepinephrine overflow during nerve stimulation. These inhibitory effects of W-7 were significantly greater in SHR than in WKY.

The results demonstrate that norepinephrine overflow from the sympathetic nerve endings and vascular responsiveness were increased in SHR. The marked reduction in norepinephrine overflow and pressor responses by W-7 might suggest the greater calmodulin-dependent adrenergic transmission in this model of hypertension.     

Exercise Training Causes Sympathoinhibition Through Antioxidant Effect in the Rostral Ventrolateral Medulla of Hypertensive Rats

Exercise training normalizes sympathetic outflow in hypertension and chronic heart failure. The aim of this study was to determine whether the exercise training inhibits sympathetic nerve activity (SNA) via reduction of oxidative stress through blocked angiotensin II type 1 receptor (AT₁R) in rostral ventrolateral medulla (RVLM). We divided stroke-prone spontaneously hypertensive rats (SHRSP) into SHRSP with exercised training (SHRSP-EX) and control (SHRSP-C). SNA and oxidative stress in the RVLM were significantly lower in SHRSP-EX than in SHRSP-C. These results suggest that exercise training inhibits SNA via reduction of oxidative stress through blocked AT₁R in the RVLM of hypertension.     

碱性成纤维细胞生长因子对自发性高血压大鼠血管平滑肌细胞肾素-血管紧张素系统的作用

以培养的自发性高血压大鼠（SHR）和正常血压（WKY）大鼠主动脉平滑肌细胞（ASMC）为模型,采用Northern印迹和逆转录-聚合酶链式反应（RT-PCR）技术分别检测ASMC中血管紧张素原（Ang N）和血管紧张素Ⅱ（Ang Ⅱ）的AT_1型受体的基因表达,并用紫外法和放射免疫法分别测定培养液中的血管紧张素Ⅰ转换酶（ACE）活性和AngⅡ的含量。结果表明,基础状态及给予外源性碱性成纤维细胞生长因子（bFGF,10 ng/ml）刺激后,SHR的ASMC中上述4种实验参数的水平均明显高于WKY大鼠。提示SHR ASMC中的肾素—血管紧张素系统（RAS）处于高功能状态;bFGF能促进Ang N基因表达、激活ACE,进而导致Ang Ⅱ生成增加,同时它对AT_1受体基因表达也有调节作用,bFGF的上述作用可能是高血压时血管RAS高功能状态发生和维持的一个重要机制。