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     

福辛普利钠对糖尿病大鼠血管反应性的影响

目的观察福辛普利钠对糖尿病大鼠血管反应性的影响。方法建立链脲左菌素所致的糖尿病大鼠血管体外灌注模型,以八导生理记录仪检测大鼠肠系膜血管反应持续时间及灌注压的变化。结果糖尿病大鼠肠系膜血管对去甲肾上腺素的反应持续时间分别为(9.50±3.1)与(5.1±2.1)s(P<0.01),最高灌压显著降低由(5.15±0.82)kPa降至(7.52±0.90)kPa(P<0.01);口服福辛普利钠8周的糖尿病组大鼠血管反应性无明显改变。结论福辛普利钠为血管紧张素转换酶(ACE)抑制剂,有保护内皮细胞依赖性血管舒张作用,使糖尿病大鼠血管反应性异常减轻。     

福辛普利对大鼠血管球囊损伤后血管紧张肽Ⅱ1型受体表达的影响

目的 :研究血管紧张肽转换酶 (ACE)抑制剂福辛普利 (fosinopril)对血管球囊损伤后血管紧张肽Ⅱ 1型受体 (AT1R)表达的影响。方法 :采用免疫组织化学技术SP法检测在大鼠髂动脉球囊损伤模型 (Clowes法[1] )中福辛普利干预后局部AT1R表达的变化。结果 :球囊损伤后d 1 4,血管中层AT1R表达 (0 .1 2 0±0 .0 1 0 )比假手术组 (0 .1 0 2± 0 .0 2 1 )显著增多 (P <0 .0 5 ) ,而此时内膜层AT1R(0 .2 82±0 .0 1 6)为中层的 2倍以上 ,福辛普利使球囊损伤后d 1 4血管AT1R(中层 0 .0 86± 0 .0 2 2 ,内膜层 0 .1 74±0 .0 1 8)表达显著减少 (P <0 .0 1 )。结论 :福辛普利能降低血管球囊损伤后AT1R表达     

去窦弓神经大鼠肥厚心室和主动脉的血管紧张素Ⅱ和AT1受体水平

AIM: Angiotensin II and AT1 receptor are the major effector components of renin-angiotensin system (RAS), andalso the main growth-stimulating factors in cardiovascular system. The present study was to observe these twofactors in the hypertrophied ventricles and aortas of sinoaortic-denervated rats. METHODS: Rats were examinedat 2, 10, and 16 weeks after sinoaortic denervation (SAD). The hypertrophy was evaluated by the ratio of organweight to body weight. Angiotensin II concentration and AT1 receptor mRNA expression were measured byradioimmunoassay and RT-PCR respectively, using a positive control of candesartan treatment. RESULTS: Aortichypertrophy existed in 2-, 10-, and 16-week SAD rats, left ventricular hypertrophy in 10- and 16-week SAD rats,and right ventricular hypertrophy in 16-week SAD rats. In all three kinds of examined SAD rats, plasma angiotensinII levels remained unchanged, indicating circulating RAS is at normal level in the chronic phase of SAD. However,cardiovascular tissue RAS was activated, as evidenced by increase of aortic angiotensin II concentrations at 10 and16 weeks after SAD, and up-regulation of aortic and left ventricular AT1 receptor mRNA expressions at 16 weeksafter SAD. CONCLUSION: The activated tissue RAS is secondary to the hypertrophy, and probably involved inthe maintenance of cardiovascular hypertrophy following SAD.     

福辛普利、替米沙坦单用或联用对糖尿病模型大鼠颈动脉内膜球囊损伤后血管紧张素转换酶2的影响研究

目的:考察福辛普利、替米沙坦单用或联用对糖尿病模型大鼠颈动脉内膜球囊损伤后血管紧张素转换酶2(ACE2)的影响及其作用机制。方法:取大鼠36只,均分为正常对照组、糖尿病模型组(蒸馏水)、球囊损伤组(蒸馏水)、福辛普利组(10mg·kg-1·d-1)、替米沙坦组(0.8mg·kg-1·d-1)和联用组(福辛普利10mg·kg-1·d-1、替米沙坦0.8mg·kg-1·d-1),每组6只,除正常对照组外,其余各组大鼠腹腔注射链脲佐菌素(35mg·kg-1)建立2型糖尿病模型。建模成功后,除糖尿病模型组外,其余各组大鼠行颈动脉内膜球囊损伤手术,手术前、后分别灌服给予相应药物1、2周,正常对照组相同时间给予蒸馏水,检测各组大鼠颈动脉中ACE2mRNA及其蛋白表达。结果:与正常对照组比较,球囊损伤组大鼠ACE2 mRNA及其蛋白表达均明显降低(P<0.05);与球囊损伤组比较,福辛普利组大鼠ACE2 mRNA及其蛋白表达没有明显差异(P>0.05),替米沙坦组和联用组大鼠ACE2mRNA及其蛋白表达明显增加(P<0.05),但2组间无显著差异(P>0.05)。结论:福辛普利并不能促进替米沙坦增强ACE2的表达;替米沙坦可能是通过增加动脉内膜局部ACE2的表达来发挥血管保护作用。     

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。     

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     

Fosinopril treatment of pregnant rats: developmental toxicity, fetal angiotensin-converting enzyme inhibition, and fetal angiotensin II receptor regulation

Pregnant women are advised against using angiotensin-converting enzyme (ACE) inhibitors due to reports of adverse effects on human fetuses. This study examined ACE binding and angiotensin II (Ang II) receptor binding in fetuses of rats treated with the ACE inhibitor fosinopril (16 mg/kg/day fosinopril, p.o. in 4 divided doses, from gestational day (gd) 13 to gd 18). Binding of the potent radiolabeled ACE inhibitor ¹²⁵I-351A to ACE in the lung and aorta of gd 19 fetuses of fosinopril-treated dams was reduced by 56 and 44%, respectively, compared to fetuses from vehicle-treated dams, indicating that fosinopril or its active metabolite, fosinoprilat, crosses the placental barrier and inhibits fetal ACE. Fetal Ang II receptor binding of ¹²⁵I-Sar¹,Ile⁸ Ang II was not altered in most of the tissues examined, although reductions in binding in the adrenal of fetuses of fosinopril-treated dams approached statistical significance.     

Effects of angiotensin I and angiotensin II in blood vessels: greater influence of converting enzyme activity in the rabbit basilar artery

We investigated the constrictor effects of Angiotensin I (Ang I) and Angiotensin II (Ang II) on rabbit peripheral (aorta, carotid artery, mesenteric artery, saphenous artery) and cerebral (basilar artery) vessels and in rat aorta in functional organ bath studies. The effect of angiotensin converting enzyme (ACE) inhibition by captopril was also assessed in these preparations. Ang II elicited concentration-dependent contractions with comparable potency in rabbit and rat endothelium-free vascular rings (pD₂ about 8.5) which indicates a lack of species and regional variation in the contractile responses to Ang II. The responses to Ang II were reduced by the presence of a functional endothelium in rabbit mesenteric artery and in rat aorta. Since ACE determines the plasma and tissue conversion of Ang I to active Ang II, we calculated the ratio R (EC₅₀ Ang I-induced contraction: EC₅₀ Ang II-induced contraction) as an indicator of the tissue ACE effectiveness. In the aorta without endothelium, Ang I was found to be much less potent than Ang II in the rabbit (R = 44) compared with the rat (R = 3.5). This species difference in the aortic conversion of Ang I to Ang II was confirmed by the use of captopril. Captopril (10^–6M) shifted the Ang I concentration/response curve by 2- and 14-fold to the right in rabbit and rat respectively. In other rabbit blood vessels, the rank order of potency to Ang I in endothelium denuded rings was basilar artery carotid artery aorta saphenous artery. In addition, the R value was the lowest for the basilar artery (R = 2.5). This is in agreement with the highest rightward shift (78-fold) of the Ang I concentration/response curve by captopril for basilar artery in comparison with only 3-, 8- and 3-fold shifts observed in carotid artery, saphenous artery and aorta respectively. In conclusion, our data provide evidence for a greater influence of ACE in rabbit basilar artery than in peripheral vessels.     

血管紧张素转换酶抑制剂治疗慢性充血性心力衰竭有效剂量探讨

目的探讨不同剂量血管紧张素转换酶抑制剂（ACEI）卡托普利治疗慢性充血性心力衰竭（CHF）疗效。方法CHF患者56例，随机分为卡托普利高剂量组n=28，150mg／d，低剂量组n=28，25mg／d，疗程24周。观察治疗前后两组临床症状、超声心动图心功能指标并记录不良反应发生情况。结果高剂量组总有效率89．3％，明显优于低剂量组60．7％（P〈0．01），左心室功能指标每搏量（SV）、心排出量（CO）、射血分数（EF）、左室短轴缩短率（FS）治疗后与治疗前比较，高剂量组有显著改善（P〈0．01），低剂量组变化不大（P〉0．05）。结论大剂量（目标剂量）ACEI较小剂量更有效改善心功能。     

AngⅡ受体阻断剂与ACEI对肾性高血压大鼠血以及血浆和组织AngⅡ含量变化的影响

目的明确血管紧张素转换酶抑制剂(ACEI)卡托普利与血管紧张素Ⅱ(AngⅡ)受体阻断剂洛沙坦二类药物的药效和作用特点。方法本实验采用①离体血管环微量生物反应测定法检测AngⅡ引起的血管收缩反应;②建立两肾一夹型高血压大鼠模型;利用颈动脉插管法和鼠尾测压计检测血压,观测急性与慢性血压的变化;③用放射免疫法检测高血压大鼠血浆与肾组织中的AngⅡ含量。结果①离体血管环实验:AngⅡ能引起剂量依赖性的血管收缩反应,卡托普利(0.1 mg/kg)对低剂量AngⅡ收缩反应有轻度的抑制效应;随着外源性AngⅡ量增多,其抑制血管收缩作用明显减弱。同样条件下洛沙坦却能完全抑制AngⅡ所引起的血管收缩反应。②在体急性降压实验:最大有效剂量的卡托普利使模型鼠的平均动脉压由(18.4±3.9)kPa降为(8.7±1.2)kPa,降压幅度达到9.6 kPa,之后给洛沙坦最大降压有效剂量(2 mg/kg),血压未再下降;改变给药顺序,平均动脉压由(16.8±1.1)kPa降为(11.4±2.4)kPa,降压幅度为5.30 kPa,然后给最大有效降压剂量的卡托普利,血压持续降为(9.3±1.8)kPa,幅度达2.12 kPa,差异具有明显的统计学意义(P<0.05)。③慢性降压实验:高血压大鼠模型给予实验因素干预后,卡托普利组平均动脉压由(18.9±2.5)kPa降为(11.8±1.6)kPa,洛沙坦平均动脉压由(19.7±2.4)kPa降为(11.7±2.0)kPa,降压幅度分别为7.19 kPa和7.93 kPa,与对照组比较差异无统计学意义。④放射免疫实验:血浆中AngⅡ含量卡托普利组为(376±72)ng/L,明显低于对照组的(526±77)ng/L,而洛沙坦组为(1 036±159)ng/L,明显高于对照组(P<0.01),二者差异具有统计学意义。肾组织中AngⅡ含量,卡托普利组(392±81)pg/g,较对照组的(431±80)pg/g降低8.9%,洛沙坦组为(294±86)pg/g,较对照组降低32.4%(P<0.05)。结论①洛沙坦是通过阻断AngⅡ受体而发挥作用,而卡托普利只能够减少内源性AngⅡ的生成,离体状态下药效弱于洛沙坦。②急性在体实验卡托普利的最大降压效应强于洛沙坦;慢性在体实验二者药效差异无统计学意义。③长期作用下,肾组织的AngⅡ水平对调节血管张力起主要的作用,血浆中AngⅡ辅助起作用。     

Effects of Digoxin on Isolated Human Mesenteric Vessels

Abstract Digoxin had contractant effects on isolated, human mesenteric arteries and veins. Veins were more sensitive to this action of the glycoside than arteries. The contractions were not affected by phentolamine or by washing with a digoxin-free solution. However, they were abolished by the calcium antagonist nifedipine, and by washing with a calcium-free medium. In the presence of digoxin, the maximum response to noradrenaline (1.8 × 10^-5 M) increased markedly in both arteries and veins, and the concentration-response curve for the amine was displaced to the left. Immersion of vein preparations in calcium-free solution for 30 min. abolished the digoxin contracture; an increase in extracellular calcium restored the response. Changes in extracellular potassium concentration caused changes in tension of the mesenteric veins similar to those previously demonstrated in peripheral veins - both in the presence and in the absence of digoxin. It is concluded that digoxin contracts mesenteric vessels by a direct action on the muscle cells, and potentiates the contractant effects of noradrenaline. These effects are dependent on the availability of extracellular calcium. Mesenteric vascular reactions caused by changes in extracellular potassium are influenced by digoxin.     

ACEI及ARB对扩张型心肌病患者生存率及心功能的影响

目的观察ACEI及ARB对扩张型心肌病患者的疗效及其差异。方法73例DCM患者随机分为ACEI组（36例）及ARB组（37例）,随访两年,记录两组出院后1、3、6、12、18及24个月时超声心动图的指标改变。结果在第3个月时,两组的LVEF均已明显升高,且改善幅度随时间持续增加,在第12个月时达到最大值并持续到第24个月。组间心功能改善无统计学差异（P〉0．05）。随访结束时,ACEI组及ARB组心源性死亡率分别为8．3％和5．4％,p=NS。ARB组不良反应更少。结论ACEI及ARB对DCM患者心功能及生存率均有肯定作用,且两者作用相似,ARB耐受性更好。     

2003年～2005年我院血管紧张素转换酶抑制剂用药情况分析

目的:分析我院血管紧张素转换酶抑制剂的用药情况及趋势。方法:用金额排序法对我院2003年~2005年血管紧张素转换酶抑制剂的用药数据进行统计分析。结果:ACE抑制剂的消耗金额逐年上升,卡托普利和贝那普利的消耗金额与用药频度居前2位。结论:合资血管紧张素转换酶抑制剂在我院的使用中占主要地位,长效血管紧张素转换酶抑制剂有良好的前景。     

The effect of the converting enzyme inhibitor HOE 498 on the renin angiotensin system of normal volunteers

Summary The converting enzyme inhibitor HOE 498 was evaluated in 12 normotensive male volunteers aged 21 to 26. The efficacy of single 5, 10 or 20 mg oral doses in blocking the pressor response to exogenous angiotensin I was tested in 3 of the subjects. All 3 doses of HOE 498 reduced the pressor response to exogenous angiotensin I to below 50% of control within 1,5 h following administration of the drug. Plasma renin and converting enzyme activity, blood angiotensin I, as well as plasma angiotensin II and aldosterone were measured serially before and up to 72 h following oral administration of a single dose of 2.5, 5, 10 or 20 mg of HOE 498 to groups of 5 volunteers each. As expected, blood angiotensin I levels and plasma renin activity rose while plasma converting enzyme activity, plasma angiotensin II and aldosterone concentration fell after administration of the drug. While the dose of 2.5 mg did not reduce plasma converting enzyme activity below 20% of control, the higher doses all resulted in plasma converting enzyme inhibition exceeding 90%. No side-effects were observed. It is concluded that in normal volunteers HOE 498 is an effective potent and long-acting converting enzyme inhibitor. Based on these preliminary findings it is expected that 5 mg HOE 948 will turn out to be adequate for therapeutic use.