福辛普利对去窦弓神经大鼠器官损伤的保护作用

目的研究血压波动性在福辛普利治疗去窦弓神经大鼠器官保护中的重要作用。方法在去窦弓神经(SAD)大鼠饲料中给予福辛普利15 mg·kg^-1·d^-1（根据体重和每日消耗的饲料总量计算，每周调整1次），16周后在清醒状态下记录24　h血压波动性，用光镜和计算机图象分析技术观察心脏、肾脏和胸主动脉的组织病理学改变。结果与SAD大鼠相比，福辛普利治疗组大鼠的血压波动性明显降低，左心室壁厚、肾小球硬化积分、心肌胶原容积分数与血压波动性呈正相关，福辛普利可明显减轻去窦弓神经大鼠引起的器官损伤。结论福辛普利长期治疗可有效减轻去窦弓神经大鼠的器官损伤。降低血压波动性在福辛普利的器官保护中可能具有重要的作用。     

卡托普利可抑制去窦弓神经大鼠引起的心肌细胞凋亡

目的 研究卡托普利对去窦弓神(SAD)大鼠心肌细胞凋亡相关基因表达的影响。方法 在去窦弓神经大鼠饲料中给予卡托普利100mg／kg／d，术后16周采用末端标记TUNEL法检测细胞凋亡；采用ABC法检测Bcl-2、Bax、Fas和Fas-L蛋白的表达，并用计算机图像分析教术进行观察和比较。结果 与SAD大鼠相比，卡托普利治疗组大鼠的心肌细胞凋亡明显减少；Bcl-2蛋白表达增加，Bax、Fas、Fas-L蛋白表达减少，Bcl-2／Bax比率增高。结论 卡托普利可减少SAD大鼠的心肌细胞凋亡，并可调节细胞凋亡相关基因的蛋白表达。     

去窦弓神经大鼠的胸主动脉重构

目的　观察大鼠去窦弓神经 (SAD)后由于血压不稳定而引起的血管重构。方法　 10wk大鼠行SAD或Sham ,术后 16周用离体动脉环实验测定SAD和相应Sham组大鼠胸主动脉对去甲肾上腺素 (NE)和氯化乙酰胆碱 (Ach)的收缩和舒张反应 ;用组织病理学和计算机图像分析技术对大鼠的胸主动脉连续切片进行观察和比较。结果　与Sham组相比 ,SAD大鼠离体胸主动脉环对NE的收缩反应增强 ,对Ach的舒张反应减弱 ;SAD组大鼠胸主动脉的结构改变主要以血管中层平滑肌细胞肥大和基质扩充为主。结论　大鼠去窦弓神经后单纯血压不稳定可引起血管重构     

血压波动性在尼群地平和阿替洛尔联合治疗自发性高血压大鼠的器官保护中的重要性

AIM: To study the importance of reduction of blood pressure variability (BPV) in the organ protection of long-term treatment with combination of nitrendipine and atenolol, which was abbreviated as Nile, in spontaneously hypertensive rats (SHR). METHODS: Combination of nitrendipine (10 mg/kg/d) and atenolol (20 mg/kg/d) was given in SHR chow for 12 weeks. Blood pressure (BP) was then recorded during 24 h in conscious state. After the determination of baroreflex sensitivity (BRS), rats were killed for organ-damage evaluation. RESULTS: Long-term treatment with Nile significantly decreased BP and BPV, ameliorated impaired BRS, and obviously diminished end-organ damage in SHR. The indices of left ventricular and aortic hypertrophy, and glomerulosclerosis score were all positively related to BP and BPV, and negatively related to BRS in untreated and Nile-treated SHR. Multiple-regression analysis showed that decrease in left ventricular and aortic hypertrophy was mainly related to the decrease in systolic BPV, and amelioration in renal lesion was mainly determined by increase in BRS. CONCLUSION: Long-term treatment with Nile possessed obvious organ protection in SHR. Besides the BP reduction, the decrease in BPV and the restoration of BRS may importantly contribute to this organ protection.     

坎替沙坦抑制大鼠去窦弓神经引起的心血管肥大

目的:研究新型AT_1受体拮抗剂坎替沙坦对大鼠去窦弓神经(SAD)引起的心血管肥大的作用及其可能机制.方法:长期治疗时,大鼠SAD术后从食物中给予坎替沙坦(6 mg·kg~(-1)·d~(-1))16周.急性治疗时,大鼠 SAD术后第 30大经胃内单次给坎替沙坦 3 mg/kg.结果:SAD大鼠坎替沙坦治疗组的左心室和主动脉肥厚指数明显低于未治疗组,相当于或低于正常水平.SAD引起的心肌肥大、纤维化、心肌内小动脉和主动脉管壁增厚以及血管内弹力膜破坏几乎被坎替沙坦完全抑制.治疗后血浆血管紧张素Ⅱ浓度明 显升高,与心血管肥厚指数呈负相关.坎替沙坦单次给药后3小时观察期内,SAD大鼠血压及其波动性维持在较低水平.结论:坎替沙坦能有效抑制SAD引起的心血管肥厚.这种心血管保护作用除与已知机制有关外,还可能与其上调循环血管紧张素Ⅱ和稳定血压有关.     

去窦弓神经大鼠心肌细胞凋亡及其相关基因蛋白表达的时程

目的:研究去窦弓神经（SAD）大鼠心肌细胞凋亡及其相关基因蛋白表达的时程。方法:10周龄SD大鼠行SAD术或假手术（Sham）,术后4、8、16和32周对SAD及相应Sham组大鼠的心肌连续切片,采用末端标记TUNEL法检测细胞凋亡;采用ABC法检测Bcl-2、Bax、Fas和Fas-L蛋白的表达,并用计算机图像分析技术进行观察和比较。结果:与Sham组相比,SAD大鼠心肌细胞凋亡率增加,Bcl-2表达减少,Bax、Fas、Fas-L表达增高,Bcl-2/Bax比率降低。结论:心肌细胞凋亡及其相关基因表达失调可能参与SAD大鼠的心肌重构,且具有一定的时间窗。     

尼群地平和卡托普利对2型糖尿病高血压患者代谢的影响

目的 :观察尼群地平 (nitrendipine)和卡托普利 (Captopir)治疗 2型糖尿病合并高血压患者对代谢的影响。结果 :两药均为有效的降压药物 ,且合用时降压作用增强。两药均可降低血清果糖胺 ,尼群地平可降低餐后 2 h胰岛素而不升高血糖 ;卡托普利可降低血糖和血尿酸。结论 :两药对总胆固醇、甘油三脂、HDL、L DL 和尿素氮 ,肌酐均无明显影响 ,也无明显副作用。     

去窦弓神经大鼠体内血管舒/缩功能的测定

目的　研究完全及部分去窦弓神经大鼠术后体内血管收缩 /舒张功能的改变。方法　用Sprague Dawley大鼠分别去除颈动脉窦神经 (SD)或主动脉神经支配 (AD) ,以及完全去除窦 弓神经支配 (SAD)。术后急性期 (1wk)、慢性期(18wk)在清醒、自由活动状态下分别测定动脉血压、心率及血压波动性、心率波动性。并分别测定上述大鼠ABR功能(ABR HP和ABR BP)。对术后 18wk的完全及部分去窦弓神经大鼠 ,通过静脉累积注射去氧肾上腺素以及硝普钠分别测定体内动脉收缩 /舒张功能。结果　术后 1wk ,SAD及AD大鼠动脉血压显著升高 ;术后 18wk ,SAD大鼠 2 4h血压平均值与对照假手术大鼠相比无差异 ,而AD大鼠血压仍较对照组明显升高。SD大鼠的血压、心率在术后 1wk及术后 18wk均无升高。术后 18wk ,SAD及AD大鼠 2 4h血压波动性较对照组大鼠升高。术后 1wk及 18wk的SAD大鼠ABR功能较对照组明显降低 ,AD大鼠ABR功能也低于对照组 ,而SD大鼠ABR功能与假手术大鼠间无差异性。术后 18wkSAD、AD和SD大鼠SBPmax(注射去氧肾上腺素后 )及DBPmin(注射硝普钠后 )较对照组大鼠均明显上升。完全及部分去窦弓神经大鼠的SBPmax和DBPmin分别与ABR功能呈负相关 ;SAD、AD及SD大鼠的ABR功能与血压波动性呈密切负相关。结论　去窦弓神经术后慢性期大     

去窦弓神经大鼠的心血管及肾脏的形态学改变(英文)

目的　研究去窦弓神经 (SAD)对正常血压大鼠的血流动力学及心、肾、血管等器官病理形态学的影响。方法　采用SD大鼠施行SAD手术 ,术后 18周行股动脉插管 ,在清醒、自由活动状态下计算机实时记录 2 4h动脉收缩压、舒张压和心率 ,并计算血压波动性 (BPV)和心率波动性 (HRV)。处死动物后 ,取心、脑、肾及脾观察大体及光学显微镜下结构变化。结果　SAD术后 18周 ,SAD大鼠的血压和心率水平与假手术组相比无显著差异 ,但 2 4hBPV明显高于假手术组 ,HRV明显低于假手术组 ;大鼠心、肾及血管有明显的类似于高血压靶器官损伤的病理改变。结论　SAD可使大鼠的心、肾和血管发生类似于高血压靶器官损伤的病理改变。     

尼群地平单用及其与美多洛尔合用对大鼠血压和胸主动脉环收缩的影响

<正> 近年来,在高血压病的治疗中,钙拮抗剂(如硝苯啶)与β受体阻断剂(如醋丁洛尔)的合用已引起关注.尼群地平(nitrendIpine,Nit)是一种较新的二氢吡啶类钙通道阻滞剂,美多洛尔(metoprolol,Met)是一种选择性β_1受体阻断剂.该二药的合用尚未见研究报道.本文采用麻醉大鼠观察     

Role of vascular K(ATP) channels in blood pressure variability after sinoaortic denervation in rats

Aim:

To investigate the role of ATP-sensitive potassium (K_ATP) channels on blood pressure variability (BPV) in sinoaortic denervated (SAD) rats.

Methods:

SAD was performed on male Sprague-Dawley rats 4 weeks before the study. mRNA expression of Kir6.1, Kir6.2 and SUR2 in aorta and mesenteric artery was determined using real-time quantitative polymerase chain reaction, and confirmed at the protein level using Western blotting and laser confocal immunofluorescence assays. Concentration-response curves of isolated aortic and mesenteric arterial rings to adenosine and pinacidil were established. Effects of K_ATP channel openers and blocker on BPV were examined in conscious SAD rats.

Results:

Aortic SUR2 expression was significantly greater, while Kir6.1 was lower, in SAD rats than in sham-operated controls. In contrast, in the mesenteric artery both SUR2 and Kir6.1 expression were markedly lower in SAD rats than controls. For both arteries, Kir6.2 expression was indistinguishable between sham-operated and SAD rats. These findings were confirmed at the protein level. Responses of the aorta to both adenosine and pinacidil were enhanced after SAD, while the mesenteric response to adenosine was attenuated. Pinacidil, diazoxide, nicorandil, and glibenclamide significantly decreased BPV.

Conclusion:

These findings indicate that expression of vascular K_ATP channels is altered by chronic SAD. These alterations influence vascular reactivity, and may play a role in the increased BPV in chronic SAD rats.     

Blood pressure variability and organ damage

1. Blood pressure variability (BPV) is expressed as the standard deviation of the average blood pressure (BP). Blood pressure variability is increased in hypertensive patients and animals. However, BPV is not necessarily related to the BP level. 2. For nearly any level of 24 h mean BP, hypertensive patients in whom the BPV is low have a lower prevalence and severity of organ damage than patients in whom the 24 h BPV is high. This observation has been confirmed further in spontaneously hypertensive rats with direct pathological analysis for organ damage. 3. In sinoaortic-denervated (SAD) rats, 24 h average BP is normal and BPV is markedly increased. Myocardial damage, renal lesions and vascular remodelling are seen in these animals 4 weeks after SAD. 4. Haemodynamic effects and activation of the renin- angiotensin system are hypothesized to contribute to organ damage induced by increased BPV. 5. Blood pressure variability is of potential importance in antihypertensive therapy.     

Frequent ventricular premature beats increase blood pressure variability in rats

INTRODUCTIONBlood pressure variability (BPV) is increased inseveral conditions, including hypertension[1-3], aging[4],diabetes[5,6], spinal cord injury[7], and alcohol consump-tion[8], and linked with the severity of the underlyingdiseases, such as hypertension[1,2]. Causes for high BPVare manifold and varied in different conditions. It iswell known that arterial baroreflex is important in thestabilization of blood pressure (BP), and interruption ofarterial baroreflex by sinoaortic d…     

Effect of captopril on renin and blood pressure in cirrhosis

Summary In hepatic cirrhosis neurohumoral vasoconstrictor systems are activated to compensate for circulatory disturbances. To study the renin-angiotensin-aldosterone system in more detail, angiotensin converting enzyme in 15 patients with advanced liver disease was inhibited with captopril after moderate sodium restriction.Captopril caused an increase in plasma renin activity (p<0.005) and a decrease in plasma aldosterone (p<0.025) from an elevated baseline, and a moderate drop in systolic (p<0.025) and diastolic (p<0.05) blood pressure. Hyperreninaemia after captopril was inversely related to the prevailing plasma sodium level (r=–0.66,p<0.01), and the changes in both systolic and diastolic blood pressure were correlated with baseline plasma renin activity (r=0.49,p<0.05 for systolic andr=0.71,p<0.01 for diastolic blood pressure). No change occurred in heart rate or in stimulated plasma noradrenaline and vasopressin levels.The data suggest that in these cirrhotic patients the reactivity of the renin-angiotensin-aldosterone system was still intact, although it occurred at a higher level. They confirm the importance of the renin-angiotensin-aldosterone system in arterial blood pressure regulation in cirrhosis.     

Inter- and intra-subject variability of nitrendipine and the effects of food

Summary Plasma concentrations of nitrendipine were measured, after single (20 mg) oral doses, in young healthy volunteers.On three occasions the subjects ingested the dose having fasted overnight. Data from these three occasions were used to assess variability in nitrendipine pharmacokinetics and both inter- and intra-subject variability were high.On a fourth occasion, the subjects took the tablet after a standard meal.The effects of food on nitrendipine pharmacokinetics, based on the comparison of data from the first fasting visit and the food visit, were negligible.     

老年与青年高血压病患者脉压和血压变异性比较

目的 比较老年和青年高血压病患者动态血压的差异,为老年高血压病患者的治疗提供依据.方法 我院高血压科就诊的83例2周内未服药的高血压病患者,60岁≤年龄＜80岁患者40例作为老年组,18岁≤年龄≤30岁患者43例作为青年组.2组患者均进行24 h动态血压监测,并比较结果.结果 老年高血压组的动态脉压、动态脉压指数和24h收缩压变异系数明显高于青年高血压组[(61±12) mm Hg(1 mm Hg=0.133 kPa)比(52 ±9)mm Hg,(0.44±0.07)比(0.37±0.06),(11±2)％比(8±2)％,均P＜0.01];24 h平均舒张压和24h平均心率明显低于青年高血压组[(79±10) mm Hg比(88±12)mm Hg,(69±8)次/mint比(74±9)次/min,均P＜0.01].结论 老年高血压病患者主要以动态脉压增大和24h收缩压变异性升高为特点;而青年患者以24h平均舒张压升高为主.因此,临床对老年高血压病患者进行降压治疗时,选择的药物不仅要有效降低平均收缩压水平,还要改善脉压和血压变异性.