巯甲丙脯酸对实验性高血压大鼠心肌缺血—再灌注损伤的保护作用

为探讨巯甲丙脯酸（ｃａｐｔｏｐｒｉｌ）对高血压肥大心肌缺血－再灌注的影响，本实验以造成大鼠腹主脉狭窄的方法复制高血压模型，观察了应用巯甲丙脯酸的高血压下大鼠离体心脏缺血－再灌注的变化，结果显示未用药的高血压大鼠，离体心脏在缺血－再灌注后出现心肌细胞乳酸脱氢酶的漏出和丙二醛生成增加及组织钙含量增加等损伤性变化，而预先应用巯甲脯酸处理的高血压大鼠，乳酸脱氢酶和丙二醛增高的情况明显减轻，避免了钙在心肌内     

尼可地尔对Langendorff大鼠心脏缺血再灌注损伤的保护作用

观察尼可地尔对Ｌａｎｇｅｎｄｏｒｆｆ大鼠心脏缺血再灌注损伤的保护作用，结果发现尼可地尔（２００μｍｏｌ·Ｌ－１）明显降低再灌注室颤发生率．抑制心肌缺血再灌注时乳酸脱氢酶的释放，减少丙二醛生成．提高超氧化物歧化酶活性，减轻细胞超微结构的损伤．提示尼可地尔对心肌缺血再灌注损伤有保护作用，其作用机理可能与抗脂质过氧化作用有关。     

蒙古黄芪总黄酮对大鼠心肌缺血再灌注损伤的保护作用

目的研究蒙古黄芪总黄酮对大鼠心肌缺血再灌注损伤的保护作用及其机制。方法采用结扎大鼠左冠状动脉前降支法,缺血90 min,再灌注24 h,建立心肌缺血再灌注损伤模型。观察大鼠心电图S-T段变化,用氯化三苯基四氮唑(TTC)对心肌染色,观察心肌梗死面积及测定血清乳酸脱氢酶、肌酸激酶、心肌组织超氧化物歧化酶、丙二醛含量,探讨蒙古黄芪总黄酮对心肌缺血再灌注损伤的保护作用。结果蒙古黄芪总黄酮90、270 mg·kg-1可以使心肌缺血再灌注损伤大鼠心电图S-T段降低及降低大鼠血清中乳酸脱氢酶、肌酸激酶的释放;30、90、270 mg·kg-1剂量可减少大鼠心肌梗死面积;270 mg·kg-1剂量减少大鼠心肌组织丙二醛的产生,提高心肌组织超氧化物歧化酶活力。结论蒙古黄芪总黄酮可以使缺血再灌注损伤大鼠心肌缺血程度降低,减少心肌梗死面积,对缺血再灌注损伤具有一定的保护作用,其作用机制可能通过抑制乳酸脱氢酶、肌酸激酶的释放,降低心肌组织氧化产物丙二醛含量、提高内源性氧自由基清除剂超氧化物歧化酶的活力,减轻缺血再灌注损伤后氧自由基对心肌细胞膜脂质过氧化损伤有关。     

7-氯苄基四氢巴马汀对离体大鼠心肌缺血再灌损伤的保护作用

目的：研究７－氯苄基四氢巴马汀对离体大鼠心肌缺血再灌损伤的影响。方法：利用Ｌａｎｇｅｎｄｏｒｆ大鼠心脏，结扎冠状动脉前降支（ＬＡＤ），缺血１０ｍｉｎ后，再灌注２０ｍｉｎ，造成缺血再灌损伤模型。结果：７－氯苄基四氢巴马汀（７－ｃｈｌｏｒＢＴＨＰ）可明显减慢心率，消除再灌注引起的心室纤颤，明显缩短心律失常持续时间，并能抑制离体大鼠心肌缺血、复灌时磷酸肌酸激酶（ＣＰＫ）及乳酸脱氢酶（ＬＤＨ）释放增加。结论：７－ｃｈｌｏｒＢＴＨＰ具有抗离体大鼠再灌注心律失常作用，对缺血再灌注损伤心肌有保护作用，其作用机制可能与其减慢心率，减少缺血复灌时心肌酶释放有关。     

双乙酰香茶菜甲素抗离体大鼠工作心脏缺血再灌注损伤的作用

目的：观察双乙酰香茶菜甲素（ＤＡＡ－Ａ）对心肌缺血再灌注损伤的作用，方法：离体大鼠心脏停灌４０ｍｉｎ，再灌２５ｍｉｎ，造成心肌缺血再灌注损伤模型，结果：ＤＡＡ－Ａ０．１３，０．２５，０．５０ｍｍｏｌ．Ｌ＾－１对再灌注所致心功能低下有心脏保护作用，降低室颤发生率及乳酸脱氢酶（ＬＤＨ），丙二醛（ＭＤＡ）的生成量，ＤＡＡ－Ａ０．２５ｍｍｏｌ．Ｌ＾－１改善心肌超微结构，结论：ＤＡＡ－Ａ抗心肌缺血再灌注损伤     

丹酚酸A对大鼠心肌缺血再灌注性损伤的保护作用

用Langendorff离体大鼠心脏缺血再灌注模型,研究了丹酚酸A(SalA)对心肌缺血再灌注性损伤的保护作用。结果显示,SalA可以降低由于心肌缺血再灌注引起的室颤发生率,减少乳酸脱氢酶(LDH)从胞体中的漏出,降低缺血心肌组织中脂质过氧化产物MDA的含量,从而证明SalA对离体大鼠心肌缺血再灌注性损伤具有一定的保护作用。     

智聪宝对离体大鼠心肌缺血———再灌注损伤的保护作用

本工作在离体灌流大鼠心肌缺血／再灌注损伤模型（Ｉ／Ｒ）上观察智聪宝的保护作用。结果发现，智聪宝灌流心脏，能显著抑制心肌缺血再灌注时心肌细胞蛋白和乳酸脱氢酶的漏出，显著减少心肌ＭＤＡ和钙聚集，显著增加冠脉流量。结果表明，智聪宝具有较好的心肌保护作用。     

双乙酰香茶菜甲素抗离体大鼠工作心脏缺血再灌注损伤的作用

目的：观察双乙酰香茶菜甲素（ＤＡＡＡ）对心肌缺血再灌注损伤的作用．方法：离体大鼠心脏停灌４０ｍｉｎ，再灌２５ｍｉｎ，造成心肌缺血再灌注损伤模型．结果：ＤＡＡＡ０１３，０２５，０５０ｍｍｏｌ·Ｌ－１对再灌注所致心功能低下有心脏保护作用，降低室颤发生率及乳酸脱氢酶（ＬＤＨ），丙二醛（ＭＤＡ）的生成量．ＤＡＡＡ０２５ｍｍｏｌ·Ｌ－１改善心肌超微结构．结论：ＤＡＡＡ抗心肌缺血再灌注损伤的作用与其抗脂质过氧化损伤有关．     

玉郎伞黄酮类化合物对大鼠离体心脏缺血再灌注损伤的作用

目的 研究玉郎伞黄酮类化合物(YLSF)对大鼠离体心脏缺血再灌注损伤的作用及其作用机制.方法 采用Langendorff法灌流离体大鼠心脏,停灌30min后再灌30min,造成心肌缺血-再灌注损伤模型.于大鼠左心室插入水囊导管,记录YLSF对血流动力学指标的影响,测定冠脉流量(CF)和冠脉流出液中肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、乳酸脱氧酶同工酶-1(LDH-1)的活性及心肌组织中超氧化物歧化酶(SOD)、丙二醛(MDA)的含量.结果 YLSF高剂量可显著改善缺血-再灌注所致大鼠的心功能损伤,减少CK、CK-MB、LDH、LDH-1的释放和MDA的产生,增加SOD的活性.结论 YLSF对心肌缺血-再灌注损伤具有保护作用,其机制可能与清除氧自由基、减少脂质过氧化反应有关.     

红景天苷对实验性心肌缺血再灌注损伤的保护作用

目的探讨红景天苷对心肌缺血再灌注损伤的影响。方法采用冠状动脉结扎法制备大鼠急性心肌缺血模型,观察红景天苷对其心电图、心肌梗死范围以及血清中酶活性的影响。结果红景天苷可以改变缺血再灌注损伤大鼠心电图S-T段的变化幅度,降低大鼠急性心肌梗死面积,抑制血清中肌酸激酶(CK)、乳酸脱氢酶(LDH)的活性,提高超氧化物歧化酶(SOD)的活力,同时降低丙二醛(MDA)的含量。结论红景天苷对心肌缺血再灌注损伤具有较好的保护作用。     

高原高血压患者血清一氧化氮的含量变化及卡托普利的干预作用

目的：观察高原高血压患者血清一氧化氮(NO)的含量及卡托普利的干预作用。方法：高原高血压患者39例在应用卡托普利(25 mg，tid，po，疗程4周)治疗前后进行NO含量的测定，并与高原健康志愿者20例进行比较。结果：高原高血压患者血清NO水平较正常对照组明显降低(P＜0.01)，经卡托普利治疗4周后血清NO水平明显升高(P＜0.05)。结论：高原高血压患者体内NO水平显著降低，卡托普利治疗后NO水平明显升高，表明NO水平的改变可能参与了高原高血压的发病过程。     

Effects of two angiotensin converting enzyme inhibitors on the mechanical function and energy metabolism of isolated rat hearts. A nuclear magnetic resonance study with an active form of benazeprilat and captopril

The effects of angiotensin converting enzyme inhibitors (ACEIs), CGS 14831 (CAS 86541-78-8) and captopril, on the mechanical function and energy metabolism were studied in isolated rat hearts using global ischemia-reperfusion model. The myocardial tissue levels of ATP, creatine phosphate (CP) and pH were determined with 31P-nuclear magnetic resonance (31P-NMR). Global ischemia was induced by cross-clamping of the inflow line for 40 min. While thiol containing ACEI, captopril, significantly inhibited the ATP depletion and pH fall produced by ischemia, non-thiol compound, CGS 14831, did not have any influence on the ATP degradation and pH fall during ischemia. Both CGS 14831 (20 micrograms/ml) and captopril (80 micrograms/ml) have little influence on the mechanical function during the ischemia-reperfusion period. L-Cysteine (44.6 micrograms/ml) inhibited the pH fall significantly during the ischemia without exerting influence on the ATP degradation. These data suggest that local renin-angiotensin-aldosterone system does not play an important role in maintenance of the myocardial mechanical function during ischemia-reperfusion. The thiol residue of captopril is not responsible for the inhibitory effect of this compound on ischemia-induced ATP degradation. Some specific effect of captopril may play a role in the protective effect.     

Captopril: pharmacology, metabolism and disposition

By inhibiting ACE, captopril blocks the conversion of AI or AII and augments the effects of bradykinin both in vitro and in vivo. In rats, dogs, and monkeys with 2-kidney renal hypertension, orally administered captopril rapidly and markedly reduces blood pressure; this antihypertensive effect apparently occurs via a renin-dependent mechanism; that is, the inhibition of ACE. In 1-kidney renal hypertension studies in rats and dogs, it was determined that oral doses of captopril markedly lowered blood pressure, but only after several days of dosing; the mechanism is thought to be non-renin dependent. In SHR, daily oral doses of captopril progressively lowered blood pressure; normal levels were attained by the sixth month. In all species studied, the reduction in blood pressure resulted from a reduction in total peripheral resistance; cardiac output remained unchanged or increased. In humans, captopril reduces blood pressure in patients with essential hypertension with low, normal, and high renin levels, and in patients with renovascular hypertension and hypertension associated with chronic renal failure. In hypertensive patients with high plasma renin activity, captopril apparently exerts most of its pharmacologic effects through inhibition of ACE. The means by which captopril reduces high blood pressure associated with low or normal PRA is not known, but it is clear that captopril does not act on an overactive plasma renin-angiotensin system in these cases. The antihypertensive effect of captopril is enhanced when it is given in combination with a diuretic or after salt depletion. Captopril was rapidly and well absorbed in all species tested, including man. Studies in rodents indicated that ingestion of food caused a reduction in the extent of absorption and bioavailability of captopril. Captopril and/or its metabolites were distributed extensively and rapidly throughout most tissues of normal rats; no radioactivity was detected in the brain. In vitro and in vivo, captopril formed disulfide bonds with albumin and other proteins. This binding was reversible in nature. In vitro studies in blood indicates that the disulfide dimer of captopril and mixed disulfides of captopril with L-cysteine and glutathione were formed. In intact blood cells, captopril remained in the reduced form (sulfhydryl), whereas in whole blood or plasma, captopril was converted to its disulfide dimer and other oxidative products. Biotransformation of captopril may involve both enzymatic and nonenzymatic processes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Study of renovascular hypertension in rats. III. Effects of converting enzyme inhibitor (captopril) on the plasma and renal renin activity in two-kidney goldblatt hypertension in rats

Two-kidney, one-clip Goldblatt models were created in Wistar rats by placing a stenotic clip around the left renal artery. A converting enzyme inhibitor, captopril was started just after operation (group 1), 4 weeks (group 2) or 12 weeks after operation (group 3). The plasma and renal renin activity (PRA and RRA) were measured by radioimmunoassay. Group 1 rats, being normotensive during captopril treatment, developed hypertension after cessation of captopril. The PRA was normal, while the RRA of ischemic kidneys was higher than that of the opposite kidneys. In group 3 rats captopril corrected hypertension in 4 of 6 rats. Although after 3 months their PRA was elevated, no difference was found in the renin content of kidneys. Group 2 rats sustained hypertension despite continued captopril treatment. These data suggest that in the early and chronic stage of this type of renovascular hypertension the renin-angiotensin system may play a major role in initiating and maintaining hypertension. In the intermediate stage (group 2), another mechanism may be involved since captopril had no effect while the pattern of the PRA and RRA of group 2 was almost the same as that of group 1.     

Dissociation of the effect of captopril on blood pressure and angiotensin converting enzyme in serum and lungs of spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain (n = 40) were treated with captopril (SQ 14,225; D-3-mercapto-2-methylpropanoyl-L-proline) orally, dose 0.2 mg/ml in drinking water. The treatment was initiated early and later during the course of developing hypertension. Continuously treated rats did not develop hypertension. Rats receiving captopril for 12 weeks remained normotensive, whereas withdrawal of the drug resulted in hypertension. Captopril treatment was effective in the rats with established hypertension and decreased the blood pressures to nearly normal values. Serum angiotensin converting enzyme (ACE) activity rose 3-fold in captopril treated rats. ACE in lung plasma membranes increased during captopril treatment, indicating that captopril induced biosynthesis of pulmonary ACE. No qualitative differences were found in the ACE from treated and not treated animals. The dissociation of the antihypertensive effect of captopril and of increased ACE activity in serum and lungs reduce the value of relating blood pressure effects of the drug to measured enzyme activity in the SHR.     

SYSTEMIC AND REGIONAL HAEMODYNAMIC PROFILE OF CAPTOPRIL IN CONSCIOUS RABBITS WITH BILATERAL CELLOPHANE PERINEPHRITIS HYPERTENSION

The radioactive microsphere technique was used to study the systemic and regional haemodynamic effects of the converting enzyme inhibitor captopril (0.1, 0.3 and 1.0 mg/kg) 10 min after intravenous administration in conscious rabbits with bilateral cellophane perinephritis hypertension, an experimental model of hypertension associated with normal plasma renin levels. Captopril lowered arterial blood pressure as a result of a dose-dependent decrease in total peripheral resistance. The fall in blood pressure was accompanied by an increase in cardiac output after the second and third dose of captopril; heart rate was not significantly altered. Captopril produced a generalized peripheral vasodilatation; the changes in vascular conductance being most pronounced in the kidneys, intestines and skin which resulted in a significant increase in blood flow to these vascular beds. The effective antihypertensive properties of captopril in this 'low plasma renin' model of hypertension and the uniform increase in vascular conductances produced by captopril, which antagonizes the generalized increase in vascular resistances that characterizes cellophane perinephritis hypertension, may indicate the involvement of an increased activity of the renin-angiotensin system, possibly in tissues, such as the vascular wall and brain, in the maintenance of the elevated blood pressure in this hypertensive form.     

缬沙坦联合卡托普利治疗尿毒症顽固性高血压

目的： 探讨治疗尿毒症顽固性高血压的有效方法。方法：尿毒症顽固性高血压病患者30例，随机分为3组，每组10例，分别服用缬沙坦(缬沙坦组)、卡托普利缓释片(卡托普利组)、缬沙坦＋卡托普利缓释片(联合组)，实验前3组均服用硝苯地平、美托洛尔。药物剂量分别为：卡托普利缓释片37.5 mg，qd；缬沙坦80 mg，qd；硝苯地平10 mg，tid；美托洛尔50 mg，tid。比较各组治疗前及治疗4周后早晨6时血压、血浆内皮素水平以及超声心动图的变化。结果：3组治疗4周后早晨6时血压、血浆内皮素水平、舒张晚期最大血流速度和舒张早期最大血流速度比值(A/E值)较治疗前均有显著下降(P＜0.01)，其中联合组较卡托普利组和缬沙坦组更显著(P＜0.01)。结论：缬沙坦、卡托普利缓释片是治疗高血压的有效药物，二者联合应用是治疗尿毒症顽固性高血压的较好方法。     

Captopril and enalapril improve cognition and depressed mood in hypertensive patients

In this study, we evaluate the effects of two angiotensin converting enzyme inhibitors (ACEIs), captopril and enalapril given chronically as antihypertensive treatment, on certain cognitive and emotional processes in humans. Thirty-nine subjects with mild to moderate hypertension and fifteen normotensive controls were divided into four groups consisting of normotensive and hypertensive subjects taking captopril, enalapril, or no medication at all. The Rey Auditory Verbal Learning Test and the Wechsler Memory Scale were used to evaluate their cognitive functioning. Mood changes in all subjects were assessed using the Beck Depression Inventory and the Hopkins Symptom Check- list (HSC). Results: Untreated hypertensive patients scored lower than normotensive controls in cognitive tests and significantly worse in cumulative recall (P < 0.05) and paired words association (P < 0.01). When compared with normotensive subjects, untreated hypertensive patients also scored significantly higher on the depression with anxiety subscale in HSC (P < 0.05). No significant influence of hypertension was found in any other examined aspect of cognition and mood. In most cases captopril improved and enalapril reversed the adverse memory effects of hypertension. High arterial blood pressure is significantly associated with an impairment of cognition and the occurrence of depression with anxiety in humans. Enalapril and, to a lesser extent, captopril reversed these deficits.     

Study of renovascular hypertension in rat. II. Effects of converting enzyme inhibitor (captopril) in the acute and chronic stages of two-kidney one-clip Goldblatt hypertension in rat

Two-kidney, one-clip Goldblatt models were produced in Wistar rats by placing a stenotic clip around the left renal artery. The animals were classified into three groups according to the time when captopril was started. In group 1 rats captopril was begun on the day following the operation and was continued for 6 weeks. During this period hypertension did not develop. In group 2 in which captopril was started 4 weeks after placement of the renal arterial clip, the blood pressure remained high as late as 12 weeks despite of continued administration of the drug. However, in group 3, captopril which was started 12 weeks postoperatively was very effective in correcting high blood pressure. In the sham operated group the blood pressure was unchanged by captopril administration. These results suggest that the role of renin-angiotensin system seems to vary according to the stages of experimental hypertension and that at least in the acute and chronic stage of two-kidney one-clip Goldblatt hypertension angiotensin II may play a major role in initiation and maintenance of high blood pressure.     

比较联合用药与单一用药治疗原发性高血压病的临床研究

目的通过观察卡托普利配合硝苯地平治疗原发性高血压病的临床疗效,研究原发性高血压病的临床用药。方法选择近期某院收治185例原发性高血压病患者为研究对象,随机分成3组。卡托普利组（A组60例）使用卡托普利,硝苯地平组（B组60例）服硝苯地平缓释片,卡托普利配合硝苯地平组（C组65例）应用卡托普利配合硝苯地平缓释片医治。结果 A组与B组疗效差异无统计学意义,C组与A,B两组疗效比较,差异有统计学意义（P〈0.05）。结论治疗原发性高血压病,联合用药优势明显,值得临床推广。