中枢及外周儿茶酚胺在大鼠一肾Grollman高血压维持期中的作用

本实验采用“8”字肾包扎法制高血压模型,尾筒法测清醒大鼠的动脉血压,测定大鼠组织中去甲肾上腺素(NE)、肾上腺素(E)及血管紧张素Ⅱ(Ang Ⅱ)的浓度。结果显示,作肾包扎大鼠的血压八周后基本维持     

BWYJ的降压作用及对血流动力学的影响

目的：观察萘哌地尔衍生物(BWYJ)对正常血压及实验性高血压模型大鼠血压的影响，采用麻醉猫观察其对血流动力学的影响，并探讨其降压机制。方法：采用肾动脉双肾双夹(2K2C)法制作大鼠肾血管性高血压模型，分别对正常及高血压大鼠静脉和口服给药，观察血压的变化；利用麻醉开胸猫测定血流动力学各项指标的变化；采用侧脑室给药、猫在体瞬膜神经肌肉标本和肾上腺素的翻转实验探讨BWYJ的降压作用机制。     

中枢儿茶酚胺与血管紧张素在一肾Grollman高血压中的作用

在一肾Grollman高血压大鼠研究了中枢儿茶酚胺(CA)与血管紧张素Ⅱ(AⅡ)于高血压的后期(维持期)听起的作用。结果发现在高血压维持期大鼠脑(延脑、下丘脑)内去甲肾上腺素(NE)、肾上腺素(E)及AⅡ含量显著高于同龄对照组。经高血压大鼠侧脑室分别注射6-OHDA与Captopril,血压均显著下降,脑内NE、E及AⅡ含量亦均显著减少。此外,发现此高血压大鼠的动脉压力反射敏感性显著降低,侧脑室注射Captopril后又明显回升。     

慢性肾性高血压大鼠脑组织磁共振成像观察和超微结构的研究

目的研究慢性肾性高血压大鼠脑核磁共振成像(MRI)的变化和相应部位超微结构的改变。方法将SD大鼠分为对照组和模型组。用双肾双夹法建立肾性高血压动物模型，术后饲养12个月，用磁共振成像结合电镜观察大鼠脑组织的变化。结果1．正常组大鼠的血压、MRI表现及超微结构未发现异常。2．慢性肾性高血压模型大鼠血压升高；侧脑室旁尾壳核区域T22WI像上可见明显的条状高信号；髓鞘结构松散，可见轴突与髓鞘间及髓鞘板层间形成宽大的裂隙，部分神经纤维缺失，髓鞘脱落。结论慢性肾性高血压大鼠脑内出现明显的条状高信号，提示脑部神经纤维的病变可能己比较严重。     

病理生理学

0502086 高血压病期长短对糖尿病人血糖、血脂代谢和微血管病变的影响；0502087 β1肾上腺素受体反义寡核苷酸治疗对肾性高血压大鼠心肌一氧化氮合成酶及凋亡的影响；0502088 β1肾上腺素能受体反义寡核苷酸对自发性高血压大鼠心肌间质及左室功能的影响；0502089 骨髓间质干细胞移植对自发性高血压大鼠心脏纤维化及心功能的影响。     

尼群地平与卡托普利对高血压鼠肾血管功能的保护作用

目的：比较尼群地平与卡托普利对高血压鼠肾血管功能的保护作用。方法：离体肾灌注试验１４周龄自发性高血压大鼠（ＳＨＲ）。结果：肾血管对去甲肾上腺素（ＮＥ）及氯化钡呈超常的收缩反应，２８周龄ＳＨＲ的超常收缩反应更为明显。但于１４周龄服用尼群地平（３０ｍｇ／ｋｇ·ｄ－１）或卡托普利（５０ｍｇ／ｋｇ·ｄ１）降压治疗１４周后ＳＨＲ，其肾血管收缩反应明显弱于对照的同龄ＳＨＲ，并接近同龄的正常血压ＷＫＹ大鼠。结论：尼群地平或卡托普利有效降压，并可逆转ＳＨＲ肾血管对缩血管物质的超常收缩反应，且两药的效应相当     

肾性高血压大鼠与心脏α1肾上腺素能受体自身抗体的关系

目的:研究肾性高血压大鼠发病与心脏α₁肾上腺素能受体自身抗体的关系。方法:利用手术的方法建立肾性高血压大鼠模型,观察心脏α₁肾上腺素能受体自身抗体与肾性高血压发病的关系,同时对自身抗体生物活性进行分析。结果:在狭窄左肾动脉两周后,大鼠血浆中心脏α₁肾上腺素能受体自身抗体的阳性率和滴度与术前相比均明显升高,并且可持续到12周,以后逐渐下降|同时心脏α₁肾上腺素能受体自身抗体对培养的乳鼠心肌细胞的跳动具有激动剂样效应。结论:心脏α₁肾上腺素能受体自身抗体可能通过作用使外周血管阻力增加,从而促进肾性高血压大鼠心肌肥厚。     

损毁大鼠中枢去甲肾上腺素能系统对海马CA3区突触形态的影响

目的:观察中枢去甲肾上腺素(NE)与海马突触形态之间的关系。方法:通过6-OHDA损毁大鼠双侧背去甲肾上腺素束来建立海马内去甲肾上腺素能系统损伤大鼠模型,于建模前后对其进行迷宫检查及类P3测定,然后对大鼠海马CA3区多形层突触界面的结构参数进行定量分析。结果:突触后膜致密物质厚度明显变薄,突出界面曲率减小、穿孔性突触的比例也有不同程度降低,突触间隙宽度加大。结论:海马内NE的正常水平对维持突触界面超微结构是必要的。     

动脉血压对缰核放电的影响

静脉注射去甲肾上腺素使血压升高,引起大鼠缰核自发放电增多,静注硝普钠使血压下降,引起缰核自发放电减少。用吗啡或芬太尼后,对自然痛刺激的痛反应—缰核放电频率增高消失,但去甲肾上腺素引起缰核放电增多效应仍然出现。提示缰核与心血管活动调节有关。     

肾性高血压大鼠主动脉HO-1表达的变化及意义

目的：为了探讨肾性高血压时血红索加氧酶(HO)／一氧化碳(CO)系统是否发生了改变，我们利用两肾一夹(2K1C)肾性高血压大鼠模型，检测了不同时期高血压大鼠HO的活性改变及4周时HO-1蛋白表达的情况，以明确血红索加氧酶在肾性高血压发病过程中的变化和作用。方法：(1)制作两肾一夹肾性高血压大鼠模型，分别于2、4、6、8周记录大鼠的血压变化，并利用放免法测定了组织和血浆中血管紧张索Ⅱ的含量；(2)利用体外反应测终产物胆红索生成量方法取大鼠主动脉测定微粒体中HO的活性；(3)取4周高血压大鼠主动脉，利用Western blot方法测定HO-1蛋白的表达情况。结果：(1)术后1周血压     

Baroreceptor and somatic sensory regulation of kidney function in two-kidney, one-clip Goldblatt hypertensive rats.

The aim of this investigation was to characterize the renal haemodynamic and tubular responses to somatic afferent nerve stimulation following the removal of afferent nerve input from the atria or the carotid sinuses in chloralose-urethane-anaesthetized Sprague-Dawley rats and two-kidney, one-clip Goldblatt hypertensive rats. Bilateral stimulation of the brachial nerve plexi at 15 V, 1.3 Hz for 0.2 ms resulted in an increase in systemic blood pressure in each group of 10-40%, while renal perfusion pressure was maintained at a constant level. There were significantly larger falls in left renal blood flow and combined left and right glomerular filtration rate in all groups following selective denervation of either the cardiopulmonary or the carotid sinus baroreceptors, respectively. Brachial nerve stimulation decreased urine flow rate and absolute and fractional sodium excretion from both kidneys in Sprague-Dawley intact animals by 53, 65 and 59%; in vagotomized animals by 68, 77 and 63%; and in carotid sinus denervated animals by 86, 90 and 48%, respectively. The renal response in the Goldblatt group were similar to the normotensive group, but the main contribution of the total response was from the untouched left kidney. The inhibitory influence of the vagus and carotid sinuses on the renal sympathetic nerve-mediated sodium and water resorption appeared to be enhanced in the Goldblatt hypertensive rats when compared with the normotensive rats. The renal functional responses to somatic afferent nerve stimulation appeared to be well preserved in the renovascular hypertensive rats, although there were important differences in the contributions to the responses from the left and right kidneys. Furthermore, the baroreceptors exerted a greater influence on basal renal function in the hypertensive rats.     

卡介苗接种对高盐及肾动脉狭窄术诱导的高血压大鼠血压的影响

目的:观察卡介苗接种对高盐负荷及肾动脉狭窄所致高血压的影响,为寻找防治人类高血压的新方法提供实验依据。方法:以高盐食物喂饲及肾动脉狭窄术分别制作高盐性高血压(SH)及肾性高血压(RH)模型。高盐喂饲或肾动脉狭窄术后4周,选择高血压大鼠及正常对照大鼠进行实验。所有大鼠腹部皮下接种卡介苗一次,接种前及接种后每周测定血压变化情况,同时每时段收集24 h尿样并以Greiss反应法进行一氧化氮终产物NO₂^-及NO₃^-(UNOx)的测定。3周后大鼠分别取主动脉组织并用Western blot法检测iNOS蛋白水平。结果:卡介苗接种对正常大鼠血压无明显影响。但接种1周时,能使高血压大鼠的血压明显下降。其中尤以卡介苗接种+L-精氨酸作用明显。NO测定表明,卡介苗接种后体内NO生成明显增加。Western blot结果证明卡介苗接种后,高血压大鼠主动脉血管组织中iNOS蛋白明显高于正常大鼠。结论:卡介苗接种能通过激活iNOS/NO途径降低某些类型高血压大鼠的血压。     

Plasma renin activity in renal hypertensive rats

Summary Plasma renin activity was estimated in normal and in renal hypertensive rats, in the unanesthetized state, in ether or in urethane anesthesia. Renal hypertension was induced by partially constricting one renal artery without touching the opposite kidney. In the unanesthetized state plasma renin activity in renal hypertensive rats was slightly, though very variably, increased (45 percent). Ether anesthesia had no influence on plasma renin activity in either normotensive or hypertensive rats. Urethane anesthesia lowered blood pressure in normotensive controls by 20 mm Hg, and caused a more than threefold increase in plasma renin activity. In renal hypertensive rats urethane depressed blood pressure by 40 mm Hg and induced a more than sixfold increase of plasma renin activity.The results suggest that the plasma renin activity in rats with renal hypertension induced by partially constricting one renal artery and leaving the contralateral kidney untouched is not necessarily augmented. This conclusion is compatible with observations in hypertensive humans with unilateral renal artery stenosis. The previous finding of a large increase of plasma renin activity in this type of experimental hypertension is an artefact due to urethane anesthesia.U. Helmchen und U. Kneissler supported by Deutsche Forschungsgemeinschaft.P. Churchill supported by National Science Foundation, Post-Doctoral Grant Number 49072, U.S.A.L. Peters-Haefeli, G. Peters and G. Schaechtelin supported by Fonds National Suisse de la Recherche Scientifique, Grant No. 53153.     

Effects of sodium chloride on early and chronic phases of malignant hypertension in rats.

Malignant hypertension was induced in Sprague-Dawley rats by a complete aortic ligation above the left renal artery. The effects of saline (0.9% NaCl) administration on the development and course of the malignant hypertensive vascular disease were studied and the treated rats were compared to non-saline-treated animals and to sham-operated controls in the early and chronic phases of the disease. In the early phase, blood pressure, hematocrit, body weight, and hypertensive vascular disease were characteristic of the malignant hypertensive process and were without significant difference in saline- and non-saline-treated animals. In contrast, the sham-operated rats remained normotensive and did not present abnormal histological findings. Plasma renin activity although decreased in the hypertensive saline-treated animals was not suppressed. In the chronic phase, NaCl administration caused an average increase of 40 g body weight during the 1-wk period this solution was given, but did not result in any improvement in blood pressure levels and vascular disease in treated rats compared to non-saline-treated animals.     

长期有氧运动增加自发性高血压大鼠肾脏内源性硫化氢的生成

BACKGROUND:It is well known that long-term aerobic exercise alleviates renal dysfunction in spontaneously hypertensive rats. However, the underlying molecular mechanism remains unclear. OBJECTIVE:To investigate the effect of long-term aerobic exercise on endogenous formation of hydrogen sulfide in the kidney of spontaneously hypertensive rats. METHODS:Rat models of long-term aerobic exercise were established and randomly assigned to four groups: Wistar-Kyoto (WKY) rat static group, WKY rat exercise group, spontaneously hypertensive rat static group and spontaneously hypertensive rat exercise group. Moderate-intensity exercise on treadmill was given for 12 weeks. At 24 hours after model establishment, weight was weighted. Blood pressure was detected in the caudal artery. Blood and urine were collected for measuring biochemical indicators related to kidney functions. The degree of glomerular sclerosis was observed. Hydrogen sulfide production activity was detected in the kidney. RT-PCR was used to detect mRNA expression levels of hydrogen sulfide production-related enzymes. Simultaneously, oxidative stress of the kidney was observed.  RESULTS AND CONCLUSION:(1) Long-term aerobic exercise obviously reduced body mass, systolic blood pressure and diastolic blood pressure, increased glomerular filtration rate and renal blood flow, decreased serum creatinine and urea nitrogen levels, urinary albumin levels, significantly reduced glomerular sclerosis score, increased hydrogen sulfide content in plasma and the rate of hydrogen sulfide formation in renal tissue, up-regulated cystathionine γ-lyase expression, obviously diminished malondialdehyde content in serum and kidney, and remarkably increased the reduced glutathione and oxidized glutathione ratio in spontaneously hypertensive rats. (2) Results indicated that long-term aerobic exercise could increase the generation of endogenous hydrogen sulfide in kidney, lessen oxidative stress in the kidney, and ameliorate renal dysfunction in spontaneously hypertensive rats.     

How useful is weight reduction in the management of hypertension?

A group of previously untreated obese hypertensive patients were started on a weight reduction programme supervised by two dietitians working in a general practice surgery. It was stressed from the beginning of the programme that reducing blood pressure was the purpose of the diet. The results of follow-up after six months are presented together with results for a control group of obese hypertensive patients not receiving dietary advice or drug therapy, but being followed by the general practitioner. The weight, systolic blood pressure and diastolic blood pressure of the dieting hypertensive group were significantly lower than those of the non-dieting group after six months. However, the drop-out rate was significantly higher for the dieting group than for the non-dieting group.

The results of a separate comparison between a control group of obese normotensive patients following the same dietary programme and the group of dieting obese hypertensive patients are also presented. Attendance rates and weight loss achieved were significantly better for the hypertensive group than for the normotensive group after 12 months.

Weight reduction appears to be an effective first-line therapy for approximately 50% of obese patients with mild to moderate hypertension, and raised blood pressure appears to provide motivation for such patients to attend a dietitian's clinic and to lose weight.

     

Once daily sotalol in the treatment of hypertension

In a small group of hypertensive patients studied at home, once daily early morning sotalol therapy effectively decreased lying, standing, and post-exercise blood pressure and pulse rate. A dose-response relationship was seen. Adverse effects were mild and transient. The once daily regimen is easy to administer and appears to give precision in blood pressure reduction. Providing there is no subsequent escape from control, once daily beta-blocking therapy should aid long-term hypertension treatment in general practice.     

The role of tumour necrosis factor-alpha in renal dysfunction following mild haemorrhage in rats

Mild haemorrhage occasionally causes delayed death following failure of kidney or multiple organs, but the precise mechanisms have not yet been identified. We investigated the role of tumour necrosis factor-alpha (TNF-alpha), known as a major pro-inflammatory cytokine that leads to multiple organ failure, on the renal damage induced by mild haemorrhage. A mild haemorrhagic state was induced in male anaesthetized rats by bleeding via a common carotid catheter for 20 min at 16.7% of total body blood, 1.09 ml/100 g body weight, without fluid resuscitation. Mean arterial pressure and heart rate decreased soon after haemorrhaging but returned to baseline level up to 5 h after bleeding. TNF-alpha mRNA expression in the kidney and serum TNF-alpha levels were highest at 1 h after bleeding. Intraperitoneal pretreatment with FR167653, an inhibitory compound of TNF-alpha production, as well as of interleukin (IL)-1beta, significantly inhibited the increase in TNF-alpha. The inflammatory cell infiltration and tubular cell injury induced by haemorrhage were suppressed, and the renal dysfunction was dramatically improved by the FR167653 treatment. The morphological changes were also less in the treated group than in those that had not been treated. TNF-alpha has been reported to have striking effects on IL-1beta release and activation of neutrophils, and to play a pivotal role in the expression of the other pro-inflammatory cytokines. Our data show that endogenously-derived TNF-alpha does play a key role in the renal dysfunction during mild haemorrhage. These results should be useful to forensic pathologists to explain the pathogenesis of renal dysfunction induced by a mild haemorrhage and to identify the cause of death where there are no significant morphological changes after mild haemorrhage.     

肾性高血压大鼠血浆ET、CGRP、AngⅡ水平变化及缬沙坦、贝那普利干预的影响

目的:研究肾性高血压大鼠血浆内皮素(ET)、降钙素基因相关肽(CGRP)、血管紧张素Ⅱ(AngⅡ)等血管活性物质的变化及降压药物缬沙坦、贝那普利干预对收缩压和ET、CGRP、AngⅡ的影响。方法:采用两肾一夹方法复制肾性高血压大鼠模型,成模大鼠随机分为缬沙坦组(30mg/kg/天,n=8)、贝那普利组(10mg/kg/天,n=8)、肾性高血压模型组(n=8);假造模大鼠作为假手术组(n=10),前两组以缬沙坦和贝那普利溶液、后两组以等量生理盐水每日灌胃。分别于术前及术后每周末测定各组大鼠收缩压变化,并在灌药治疗8周后用放免法测定各组血浆ET、CGRP、AngⅡ含量变化。结果:两肾一夹术后4周可形成稳定肾性高血压大鼠模型。缬沙坦组、贝那普利组大鼠经灌胃治疗8周后血压明显下降(P<0.01)。肾性高血压模型组ET、CGRP、AngⅡ血浆浓度均高于假手术组(P<0.05或P<0.01);缬沙坦组、贝那普利组CGRP浓度高于肾性高血压模型组(P<0.05),贝那普利组AngⅡ浓度低于肾性高血压模型组和缬沙坦组(P<0.05);肾性高血压模型组血浆ET与AngⅡ浓度呈正相关(r=0.62,P<0.05)。结论:肾性高血压大鼠血浆ET、CGRP、AngⅡ浓度增高,缬沙坦、贝那普利可能通过调节血管活性物质水平而降低收缩压。     

Posture, Place, and Mood Effects on Ambulatory Blood Pressure

Ambulatory blood pressure was studied as a function of posture, place, and mood in 131 subjects classified according to race, gender, and hypertensive status. The effect of posture was significant and explained a substantial proportion of within-subject variability. After controlling for posture, significant place and mood effects were observed when subjects were sitting but not when they were standing. Home vs. work differences in both systolic and diastolic blood pressure were significantly greater in Whites than in Blacks. Similar differences in systolic blood pressure were greater in mild hypertensive than in normotensive subjects. The results of this study underscore the need to control for effects of posture when interpreting ambulatory blood pressure readings.