内源性中枢血管紧张素Ⅱ在慢性应激大鼠血压高反应性中的作用

心理生理学研究表明,高血压病人对应激刺激的反应性要高于正常血压者,高血压息者对刺激产生的血压变化在幅度与时限上均强于正常血压者。动物实验表明,与Wistar-Kyoto(WKY)大鼠相比,自发性高血压大鼠(SHR)对环境心理应激的心血管反应性增强,并可能与遗传有关。在SHR的高血压维持中血管紧张素Ⅱ(AⅡ)起一定作用。本实验探讨内源性中枢AⅡ在慢性应激Wistar大鼠动脉血压高反应     

自发性高血压大鼠中枢血管紧张素Ⅱ的变化对中枢肾上腺素...

The content of norepinephrine (NE) and epinephrine (E) in the brain of spontaneously hypertensive rats has proved abnormal, but the cause remained unknown. It was shown in the recent work that NE content in pons, posterior hypothalamus, nucleus caudatus and E concentration in medulla oblongata, anterior and posterior hypothalamus of 12-week old stroke-prone spontaneously hypertensive rats (SHRSP) were much higher than those of age-matched Wister-Kyoto rats (WKY). SHRSP also showed higher levels of systolic blood pressure (SBP) and brain angiotensin II (A II) than WKY. Intracerebroventricular (icv) perfusion of angiotensin-converting enzyme inhibitor captopril (20 micrograms for each time and three times for each day for four weeks) inhibited the synthesis of brain A II and reduced SBP and NE, E contents in all examined brain areas in SHRSP and WKY. However, the effects of chronically perfused captopril on SBP and brain NE, E levels in SHRSP were much more significant than in WKY. The results indicate that the modulatory effects of central renin-angiotensin system (RAS) on central adrenergic and noradrenergic system might be overactivated in SHRSP, which might partially responsible for the abnormally high levels of NE, E in some of the brain areas of SHRSP.     

血管紧张素受体1在血管紧张素Ⅱ诱导人星形胶质细胞老化中的作用

目的通过体外细胞实验研究,探讨血管紧张素受体1在血管紧张素Ⅱ诱导人星形胶质细胞活性氧产生和细胞老化中的作用。方法人星形胶质细胞随机分为三组：血管紧张素Ⅱ＋Cand（坎地沙坦）组和血管紧张素Ⅱ＋tempol组。血管紧张素Ⅱ组是用100nM血管紧张素Ⅱ刺激人星形胶质细胞3天,血管紧张素Ⅱ＋Cand组和血管紧张素Ⅱ＋tempol组先用血管紧张素受体1阻滞剂坎地沙坦（100nM）和氧自由基清除剂tempol（3mM）预处理,再用100nM血管紧张素II刺激人星形胶质细胞3天,利用β半乳糖苷酶染色评估细胞老化。不同剂量（0、1nM、10nM、100nM、1000nM和1000nM＋坎地沙坦）的血管紧张素Ⅱ刺激人星形胶质细胞30min,DHE染色评估细胞内活性氧产生。结果血管紧张素Ⅱ引起人星形胶质细胞DHE染色表达增多和β半乳糖苷酶染色细胞增多。利用血管紧张素受体1阻滞剂坎地沙坦和氧自由基清除剂tempol预处理逆转了血管紧张素Ⅱ引起的星形胶质细胞老化。结论血紧张素Ⅱ是通过血管紧张素受体1和超氧阴离子产生引起星形胶质细胞的老化。     

血管紧张素Ⅱ在紧张应激引起大鼠血压升高中的作用

实验在雄性Sprague Dawley大鼠上进行。实验动物被随机分为对照组、应激组和应激 腹腔注射卡托普利 (captopril)组。应激组大鼠每天给予电击足底结合噪声的应激刺激 ,每日 2次 ,每次 2h ,连续 15d ;应激 ipcaptopril组大鼠在给予应激刺激期间 ,经腹腔内注射captopril 5 0mg/kg d。实验结果观察到 ,15d后 ,三组大鼠平均尾动脉收缩压分别为 :对照组 16 32± 0 5 5kPa (n =7) ,应激组 19 75± 1 0kPa (n =8) ,应激 ipcaptopril组17 6 9± 1 0 7kPa (n =8)。应激 ipcaptopril组大鼠的尾动脉收缩压较对照组动物有显著升高 (P <0 0 5 ) ,但又显著低于应激组大鼠 (P <0 0 5 ) ;同时 ,三组大鼠下丘脑组织中AVP mRNA水平分别为 :对照组 7332 6 6± 5 2 2 6 5 (n =6 ) ;应激组 12 990 33± 15 33 5 8(n =6 ) ,应激 ipcaptopril组 10 6 15 5± 1410 49(n =6 )。应激 ipcaptopril组大鼠下丘脑组织中AVP mRNA水平较对照组有显著升高 (P <0 0 0 1) ,但又显著低于单纯应激组大鼠 (P <0 0 5 )。统计结果显示 :各组大鼠下丘脑组织中AVP mRNA水平与血压之间存在正相关关系 (P <0 0 0 1)。对照组大鼠在侧脑室注射 (icv)选择性血管升压素 (AVP)V1受体拮抗剂d(CH2 ) 5Tyr(Me)AVP 0 3μg后 ,其平均动脉压 (     

血管紧张素Ⅱ对家兔心率变异的影响

目的:研究血管紧张Ⅱ(AngⅡ)对家兔心率变异(HRV)影响的机制。方法:分别给家兔静脉输注生理盐水,AngⅡ,溴化六烃季胺(HEXB),HEXB+AngⅡ检测安静状态下连续5 min的心电图并进行HRV的时域和频域分析。结果:血管紧张素Ⅱ组的时域指标SDNN和RMSSD较对照组明显降低,频域指标低频(LF)升高,而高频(HF)和总功率(TP)明显降低;HEXB+AngⅡ组与HEXB组相比无明显区别。结论:交感神经阻断剂HEXB不能影响AngⅡ的作用,AngⅡ主要通过抑制中枢自主神经的传出,降低迷走神经张力来降低HRV。     

雌激素在中枢肾素-血管紧张素系统功能异常诱导的高血压中的保护作用

雌激素主要由卵巢分泌,是一种类固醇激素。流行病学研究显示,绝经前女性的高血压发病率明显低于同龄男性。研究表明,雌激素可通过影响中枢肾素-血管紧张素系统(RAS)组分的功能发挥其在中枢血压调控中的保护作用。雌激素作用于雌激素受体可抑制RAS增压信号通路或/和激活其减压信号通路,衰减中枢核团内自主神经元兴奋性进而延缓外界刺激诱导的高血压的发生。本文通过对雌激素在中枢RAS活动增强诱导的高血压发生中心血管保护作用及作用机制等方面进行综述,为临床开展性别差异性的高血压防治提供新思路。     

血管紧张素转换酶2-血管紧张素1-7-Mas轴对血管作用的研究进展

血管紧张素转换酶2（ACE2）和Mas受体的发现使人们对肾素-血管紧张素（RAS）有了更全面的认识。ACE2可水解血管紧张素Ⅰ和血管紧张素Ⅱ直接或间接生成血管紧张素1-7（Ang 1-7）,并与高血压的形成密切相关。Ang 1-7主要通过Mas受体引起血管舒张、抑制细胞增殖。ACE2-Ang1-7-Mas轴的发现为RAS的研究、高血压等心血管疾病的防治和新药开发提供了新的思路和方向。     

血管紧张素Ⅱ在小鼠卵泡闭锁中的作用

应用幼年小鼠经孕马血清促性腺激素（pregnant mares serum gonadotropin,PMSG)处理的动物模型,研究了卵泡从发育到闭锁动态变化过程中血管紧张素Ⅱ（AngⅡ）的作用。结果表明：（1）24日龄小鼠给予PMSG（10IU/只）后6d时,卵巢中出现大量闭锁卵泡,颗粒细胞DNA琼脂糖电泳显示了梯形条带;（2）随卵泡闭锁发生,卵巢AngⅡ含量增加;（3）AngⅡ显著拮抗FSH刺激颗粒细胞雌二醇生成的作用。我们认为,AngⅡ参与了对小鼠卵泡闭锁的调节。     

血管紧张素Ⅱ信号传导研究进展

ＡＮＧⅡ经ＡＴ１受体除激活经典的磷酯酶Ｃ等通路外,新发现还可转移激活表皮生长因子（ＥＧＦ）等生长因子受体及胞浆的ＦＡＫ、Ｓｒｃ、ＪＡＫ等酪氨酸激酶,介导细胞的粘附、肥大和增殖。此外,ＡｎｇⅡ经ＡＴ２受体可激活多种磷酸酯酶脱磷酸化,抑制细胞生长,诱导调亡,产生对抗ＡＴ１效应。     

The effect of the central iso-renin angiotensin system on pressor responsiveness to angiotensin II

The effect of intraventricular (IVT) infusion of a subpressor dose (6.25 or 12.5 ng/kg/min) of angiotensin II (AII) on the pressor responses to intravenous (IV) infusion of AII were studied in pentobarbital anesthetized rats. This study was undertaken to determine whether the central iso-renin angiotensin system alters pressor responsiveness to IV infused AII. Pressor responses to IV infusion of AII were potentiated by concurrent IVT infusion of a subpressor dose of AII. IVT pressor doses of AII decreased plasma renin activity, however, IVT subpressor doses of AII did not. These results suggest that the central iso-renin angiotensin system plays an important role in pressor responsiveness to IV AII and that the potentiation of IV AII is not related to decreases in endogenous AII as a result of IVT administered AII.     

Attenuation by naloxone of the pressor effects of angiotensin II in conscious cynomolgus monkeys

The effects of naloxone and morphine on mean arterial blood pressure (MBP) and heart rate (HR) responses to angiotensin II (AII) were studied in conscious cynomolgus monkeys. Graded doses of AII (0.3, 1 and 3 micrograms/min for 8-10 min) were infused i.v. 20 min apart, preceded by an i.v. injection of either naloxone (1, 3 or 10 mg/kg), morphine (0.3, 1 or 3 mg/kg) or saline. Pretreatment with naloxone (10 mg/kg) attenuated the pressor response to AII (0.3 or 1 microgram/min) by 25-50% but did not alter similar pressor responses to phenylephrine. Pretreatment with morphine had little or no effect on MBP or HR responses to AII.     

Are polyamines involved in the contractile effects of angiotensin II in the rat aorta? (Polyamines and angiotensin II in rat aorta).

Angiotensin II (AII) is a central factor involved in the pathophysiology of arterial hypertension and atherosclerosis. On the other hand, polyamines represent a family of organic cations with low molecular weight, playing intracellular regulatory roles essential for the cellular growth and differentiation. The cellular contents, the synthesis and the transport of polyamines are increased following the actions of AII, as well as of other cellular growth factors. Our results show that the administration of polyamines as pre-treatment modulates the contractile effects of extracellular AII (80 nM). This modulation is concentration-dependent and dual: the lower concentrations amplify and the higher concentrations reduce the effects of AII in the isolated rat aorta rings without endothelium. Moreover, DL-alpha-Difluoromethylomithine (DFMO), a specific inhibitor of ornithine decarboxylase, does not significantly modify the contractile effects of AII. Thus, these data suggest that polyamines generated through this metabolic pathway are not involved in the contractile effects of AII in rat aortic vascular smooth muscle.     

Peripheral administration of AT1 receptor blockers and pressor responses to central angiotensin II and sodium.

Central administration of AT1 receptor blockers prevents salt-sensitive hypertension and inhibits progression of CHF. We investigated in Wistar rats the effectiveness of peripheral administration of two AT1 receptor blockers, losartan and embusartan, in exerting central AT1 receptor blockade. Losartan or embusartan at doses of 30 and 100 mg/kg were administered subcutaneously (s.c.) as a single dose, or one dose daily for 6 days. The BP responses to intracerebroventricular (i.c.v.) injection of Ang II, i.c.v. infusion of Na+-rich aCSF (0.3 M NaCl), and intravenous (i.v.) injection of Ang II were then measured. Losartan or embusartan at 30 and 100 mg/kg both inhibited the BP increases induced by i.c.v. Ang II and, to a lesser extent, by Na+-rich aCSF. After a single dose, this inhibition was more pronounced for losartan. However, after 6 days of treatment, there were no significant differences between the effects of losartan and embusartan. Losartan and embusartan blocked responses to Ang II i.v. to a similar extent. These results indicate that results from single-dose studies may not reflect the chronic steady-state, and that during chronic treatment both AT1 receptor blockers are similarly effective in inhibiting AT1 receptors in the central nervous system, when assessed by pressor responses to acute increases in CSF Na+ or CSF Ang II.     

The effect of hypothermia on the cardiovascular system and the pressor actions of angiotensin II

1. 1.|The effect of hypothermia (24°C) on the pressor action of angiotensin II (ANG II) was studied in anaesthetized rats.

2. 2.|Hypothermia prolonged the pressor response to ANG II leading to an increase in the estimated half-life of ANG II.

3. 3.|Hypothermia also caused a significant increase in stroke volume and a significant decrease in heart rate with no change in cardiac output.

4. 4.|It is conclued that hypothermia causes a prolongation of the pressor action of ANG II probably by reducing the activity of the catabolic enzymes leading to an increase in ANG II half-life.