Brain Angiotensin II Receptor Subtypes and the Control of Luteinizing Hormone and Prolactin Secretion in Female Rats

The present experiments examined the role of the two recently identified angiotensin II (Ang II) receptor subtypes, AT, and AT(2) , in the central nervous system regulation of luteinizing hormone (LH) and prolactin secretion in estrogen- and progesterone-treated ovariectomized rats. In this animal model, intracerebroventricular (icv) injection of Ang II stimulates LH and inhibits prolactin release. The specific Ang II receptor subtype antagonists losartan (AT(1) ) or PD123177 (AT(2) ) were administered (icv) in various doses (10 ng to 1,000 ng) 10 min prior to icv injection of Ang II (100 ng). Control animals were pretreated with artificial cerebrospinal fluid prior to Ang II administration. Blood samples for LH and prolactin determinations were taken from conscious, freely-moving rats prior to and following injection of the antagonists and Ang II. Water intake was measured. Ang ll-induced water intake was attenuated 62% by 1,000 ng losartan; water intake was not affected by lower doses of losartan or by any dose of PD123177. Ang ll-induced stimulation of LH release was abolished by the 1,000 ng doses of losartan and PD123177 and attenuated by the 500 ng doses of both drugs. Lower doses did not affect Ang ll-induced LH secretion. Ang ll-induced inhibition of prolactin release was significantly reduced by the 1,000 ng doses of both losartan and PD123177. Lower doses of either drug did not affect the Ang II inhibition of prolactin release. Previous studies had shown that Ang II administration into the anterior hypothalamus-medial preoptic (AHPO) area stimulated LH release. This brain area contains AT(1) receptors. To investigate the potential brain site where the AT(2) receptor may influence LH release, Ang II was injected into the locus ceruleus, a brain nucleus which contains predominately the AT(2) receptor subtype. Ang II administration into the locus ceruleus was paired with an injection of artificial cerebrospinal fluid or Ang II into the AHPO area. Injection of Ang II into the AHPO area stimulated LH release. Injection into the locus ceruleus did not affect LH secretion, nor did it modify the rise in LH elicited by administration of Ang II into the AHPO area. Plasma levels of prolactin were not altered by any of these injections. Taken together, these data demonstrate that, in estrogen- and progesterone-treated female rats, icv Ang ll-induced water intake is mediated by the AT, receptor subtype, while Ang ll-induced changes in LH and prolactin secretion appear to be mediated by both the AT(2) and AT(2) receptor subtypes. The latter observations are one of the first suggesting a potential function for the AT(2) subtype in vivo, although the physiological relevance of this observation, as well as the site of action for the effects on LH and prolactin, remain to be established.     

平胃散对湿阻中焦模型大鼠血浆抗利尿激素及红细胞内钠、钾浓度的影响

目的:探索湿阻中焦证的病理机制,并探讨平胃散对湿阻中焦证的作用机理。方法:选用湿阻中焦证大鼠模型,给予平胃散配伍利水药,观测各组大鼠血浆抗利尿激素(ADH)的浓度及红细胞内电解质Na~+、K~+浓度。结果:湿阻造模组大鼠与正常组相比ADH显著升高(P<0.01);细胞内的Na~+增高,K~+显著降低(P<0.05)。给予平胃散后,高、中、低剂量组及加泽泻组大鼠ADH基本恢复正常;细胞内的Na~+下降至接近于正常,K~+尤明显变化;不造模给药组与正常组比较ADH显著升高(P<0.05),Na~+、K~+明显下降(P均<0.01)。结论:(1)血浆ADH浓度升高、细胞内Na~+增多、K~+降低在湿阻中焦证形成中起重要作用。(2)平胃散治疗湿阻中焦证的作用机理与调节ADH和细胞内Na~+、K~+浓度有关,且可能存在双向调节机制。     

卡托普利对Langendorff灌注大鼠全心缺血-再灌注损伤的保护作用

目的：探讨卡托普利对Langendorff灌注大鼠全心缺血-再灌注损伤的保护作用及机制。方法：采用Langendorff离体全心灌流装置，模拟缺血-再灌注，观察卡托普利对大鼠全心缺血-再灌注引起的心律失常的作用及体内CPK、LDH、MDA、SOD及AngⅡ含量的变化。结果：卡托普利减少缺血及再灌注期心律失常的发生，加快再灌注期高度房室传导阻滞的恢复。缺血期：CPK及LDH缺血-再灌注(B组)组较对照组(A组)明显增加，卡托普利治疗组(C组)较B组显著降低，再灌注期：CPK及LDH B组较A组明显增加，C组较B组明显降低，心肌组织MDA，Ang II的含量B组明显高于A组，C组明显低于B组，而SOD含量两组比较无显著性差异。结论：卡托普利具有拮抗离体大鼠全心缺血一再灌注损伤的作用，拮抗作用是通过抑制血管紧张素转换酶(ACE)而抑制Ang II的生成，抑制氧自由基的产生而实现的。     

Ca~(2+)经钙激活非选择性阳离子通道进入ECV304内皮细胞

目的　研究钙离子进入ECV30 4内皮细胞株的途径和血管紧张素Ⅱ (AⅡ )对钙内流的影响。方法　用膜片钳的细胞贴附式和全细胞方式记录ECV30 4内皮细胞的通道活动。结果　 (1 )在记录单通道电流时电极液含 1 2 0mmol·L- 1 CaCl2 ,细胞浴液不含K+ 、Na+ 时 ,Ca2 + 经非选择性阳离子通道 (CAN)内流的电导为γ0 =(1 2 90± 2 1 1 ) pS(n =4)。1× 1 0 - 7mol·L- 1 AⅡ可显著增强通道电流幅度和延长通道开放时 ,其电导增大为γ1 =(2 2 1 8± 2 2 9)pS(n =4)。全细胞记录得到的结果与单通道的一致。 (2 )用全细胞方式记录到ECV30 4内皮细胞的电压依赖性钙通道电流 ,记录到该峰值电流为 (2 9 32± 3 56)pA(n =4) ,2 0 μmol·L- 1 nifedepine能抑制这个峰值电流 ,被抑制后的电流峰值为 (6 0 0± 3 94)pA(n =4)。 2 μmol·L- 1 BayK8644能显著激活通道活动。结论　Ca2 + 经CAN进入ECV30 4细胞 ,AⅡ可显著增强CAN的钙流     

血管紧张肽转换酶抑制剂对高血压病人心脏和大动脉的影响

目的 :评价血管紧张肽转换酶 (ACE)抑制剂对原发性高血压病人心脏和大动脉结构和功能的影响。方法 :应用二维超声、超声心动图及自动脉搏波传导速度 (PWV)测定仪观察 16例采用ACE抑制剂培哚普利治疗 (4mg ,po ,qd ;4wk后若血压 >18.6 / 12 .0kPa ,加服吲哒帕胺 2 .5mg ,po ,qd)的原发性高血压病人心脏、大动脉结构和功能的改变 ,分别在治疗前和治疗 12wk后进行上述检测。结果 :收缩压、脉压、颈动脉 股动脉PWV、颈总动脉内膜 中层厚度和左室后壁厚度在 12wk培哚普利治疗后显著降低 [分别为 (2 0 .4±s 1.4 )kPavs (18.0± 1.2 )kPa ,(7.5± 1.1)kPavs (6 .9± 1.2 )kPa ,(10 .5± 1.3)m·s- 1vs (8.6± 1.0 )m·s- 1,(0 .71± 0 .14 )mmvs (0 .5 9± 0 .14 )mm ,(10 .5± 1.0 )mmvs (9.8± 1.0 )mm ,P <0 .0 1或P <0 .0 5 ];颈总动脉横断面顺应性、容积扩张性在治疗前后无显著性差异(P >0 .0 5 )。结论 :培哚普利对心血管系统的影响不仅仅是与血压降低有关 ,药物引起动脉平滑肌松驰 ,对全身和局部肾素 血管紧张肽系统的抑制能有效地改善高血压导致的心脏、血管结构和功能的改变。     

血管紧张素转换酶抑制剂的临床应用进展

就近年来血管紧张素转换酶抑制剂(ACEI)在临床应用、不良反应、费用-效益分析方面的进展进行了综述，并进行讨论，表明ACEI具有广泛的应用。     

男性生殖系统的肾素-血管紧张素系统与某些精子功能的关系

在男性生殖系统中已发现有多处存在肾素-血管紧张素系统(renin-angiotensin system,RAS),RAS被认为可能在男性生殖调节中发挥重要作用。本文就RAS中的血管紧张素转化酶和血管紧张素Ⅱ对某些精子功能,主要包括精子活动力、精子顶体反应和精-卵相互作用等方面的影响作一文献综述。     

甘草次酸对血管平滑肌细胞c-fos mRNA表达及细胞增殖的影响

目的　研究甘草次酸 (GA)对大鼠血管平滑肌细胞(VSMC)原癌基因c fosmRNA表达及细胞增殖的影响 ,探讨GA与血管紧张素Ⅱ (AⅡ )受体结合的可能机制。方法　原代培养大鼠血管平滑肌细胞 ,[3H]TdR参入DNA、MTT分析法、Northernblot。结果　①低浓度GA( 1× 10 -9mol·L-1)及高浓度GA( 1× 10 -5mol·L-1)均能导致c fosmRNA迅速表达 ;1× 10 -5mol·L-1Sar AⅡ能够阻断AⅡ、GA诱导的VSMCc fos表达 ;低浓度和高浓度GA都能促进AⅡ ( 1× 10 -5mol·L-1)诱导的VSMCc fos表达 ;②低浓度GA对细胞的增殖有促进作用 ;随着浓度的升高 ,促增殖作用减弱 ;高浓度GA抑制细胞的增殖。Sar AⅡ单独作用于VSMC ,不影响细胞增殖 ;Sar AⅡ能够阻断AⅡ对细胞增殖的促进作用 ;Sar AⅡ既抑制低浓度GA促细胞增殖作用 ,也消除高浓度GA抑制细胞增殖作用 ;低浓度GA与AⅡ联合作用 ,对细胞增殖的促进作用更加显著 ;高浓度GA与AⅡ联合作用于VSMC ,则可减轻高浓度GA对细胞增殖的抑制作用。结论　GA能激活c fos转录因子 ,从而产生对VSMC的增殖作用 ,因此 ,GA具有AT1受体的激动剂2 0 0 2 0 4 0 3收稿 ,2 0 0 2 0 7 2 3修回作者简介 :张凤云 ,女 ,33岁 ,硕士 ;贺师鹏 ,男 ,67岁 ,教授。研究方向 :酶和受体的拮抗剂样作用     

血管紧张素Ⅱ和氯沙坦对大鼠小动脉平滑肌细胞的基质金属蛋白酶2和9表达的影响

目的　为研究血管紧张素Ⅱ导致血管重构的机制是否与其影响平滑肌细胞的基质金属蛋白酶 2和 9的表达及活性有关。方法　应用RT PCR、Westernblot、明胶酶谱分析等方法观察不同浓度的血管紧张素Ⅱ对体外培养的大鼠肠系膜小动脉平滑肌细胞的金属蛋白酶 2和 9的表达及活性的影响。结果　高浓度的血管紧张素Ⅱ作用VSMC 48h时 ,可以诱导金属蛋白酶 2和 9的表达及活性增加。不同浓度影响程度不同 ,1× 10 - 8mol·L- 1和 1× 10 - 7mol·L- 1的血管紧张素Ⅱ影响最强。 1× 10 - 6 mol·L- 1氯沙坦可以部分阻断血管紧张素Ⅱ对金属蛋白酶 2和 9的诱导作用。结论　血管紧张素Ⅱ可以诱导小动脉VSMC的金属蛋白酶 2和 9的表达及活性增加 ;AT1受体参与介导此过程     

血管紧张素Ⅱ诱导培养的牛脑微血管内皮细胞凋亡及其机制

目的　研究AngⅡ对牛脑微血管内皮细胞(BCMEC)有无诱导凋亡的作用。方法　利用流式细胞仪和透射电子显微镜检测体外培养的BCMEC凋亡。结果　流式细胞术显示AngⅡ (0 .0 1～ 10 μmol·L- 1)呈浓度依赖性诱导BCMEC凋亡。 10 μmol·L- 1AngⅡ诱导的BCMEC凋亡不能被 10 0 μmol·L- 1AT1受体拮抗剂氯沙坦所抑制 ,而能被 15 0kU·L- 1超氧化物歧化酶所部分抑制。BCMEC经 10 μmol·L- 1AngⅡ刺激 18h后 ,呈现胞浆浓缩、染色质凝集、核碎裂和凋亡小体形成等凋亡的超微结构变化。结论AngⅡ能诱导BCMEC凋亡 ,其机制可能与其刺激BCMEC产生的氧自由基有关。AngⅡ诱导脑血管内皮细胞凋亡可能是其参与脑血管疾病的机制之一