甲巯丙脯酸在高血压病中的临床应用

甲巯丙脯酸(Captopril,SQ_(14226))的化学名称是D—2一甲基—3巯基丙酰—L—脯氨酸,1976年人工合成,是第一个口服有效的血管紧张素转换酶抑制剂(ACEI)。从1978年首次用于临床治疗高血压病至今已十年。本文就甲巯丙脯酸在高血压病临床应用的目前概况作一综述。一、药理作用 (一)对肾素—血管紧张素—醛固酮系统(RAAS)的作用甲巯丙脯酸的主要药理作用是抑制血管紧张素转换酶(ACE),使无活性的十肽血管紧张素Ⅰ(ATⅠ)转化为有高度血管收缩活性的八肽血管紧张素Ⅱ(ATⅡ)减少。这是甲巯丙脯酸的主要降压机理。由于血浆ATⅡ浓度     

小剂量甲巯丙脯酸,利尿剂治疗重度原发性高血压的探讨

102例重度原发性高血压患者随机分为4组:A 组为甲巯丙脯酸(CPT)75mg/日;B 组为CPT150mg/日;C 组为CPT75mg/日+利尿剂;D 组为CPT150mg/日+利尿剂。治疗4周总有效率分别为50.0%,56.0%,85.7%及82.6%,C 组和D 组明显高于A 组和B 组(P 均<0.05)。部分病例尿蛋白缓解。1例发生可逆性肾功能恶化,无高钾血症。提示这类患者CPT75mg/日+利尿剂治疗一般是安全而有效的,但宜监测血压和血钾。     

甲巯丙脯酸对难治性心力衰竭的治疗作用及其不良反应

本文报告40例狄戈辛、利尿剂联合治疗无效的难治慢性心衰患者,加用甲巯丙脯酸后总有效率为70%,未发现有洋地黄心脏中毒者。但肾功能恶化和高钾血症比较明显,主要见于老年患者。血钾升高及肾功能损害与并用滞钾利尿剂或氯化钾有关,而肾功能恶化可能是由于肾脏血流动力学改变所致。     

不同类型Goldblatt高血压大鼠对MK-421的降压反应

MK-421, a new angiotensin-Ⅰ converting enzyme inhibitor, was found to reduce the blood pressure in one-kidney, one-clip hypertensive rats at 30 mg/kg po (n=12). On the 5 th day and the 5 th week after renal artery constriction the blood pressure decreased from 196±14 and 250±5 mmHg pretreatment to 159±28 and 225±3 mmHg respectively (p<0.001 and 0.05 respectively) and maintained the level about 8 hours. After treatment with MK-421,angiotensin-Ⅰ converting enzyme activity was significantly inhibited. Similarly, MK-421 (30 mg/kg po) also decreased the blood pressure in two-kidney, one-clip hypertensive rats (n=18) on the 5th day and the 5th week after operation. The blood pressure decreased from 162±20 and 217±20 mmHg to 117±24 and 120±28 mmHg respectively and reduced to preoperation normortensive level(113±5 mmHg). These results indicate that renin-angiotensin systemmightplay an important role in the pathogenesis of two-kidney one-clip hypertensive rats. However, besides renin-angiotensive system, there are other mechanisms involved in the pathogenesis of one-kidney,one-clip hypertensive rats.     

不同类型Goldblatt高血压大鼠对MK-421的降压反应

肾素—血管紧张素系统(RAS)与高血压发病机理密切相关。然而在不同高血压模型以及同一模型不同时期RAS在其发病中所起的作用大小不一。我们曾经报道血管紧张素Ⅰ转换酶(ACE)抑制剂巯甲丙脯酸灌胃能明显降低二肾一夹(2 K1C)型高血压大鼠的血压,但不降低一肾一夹(IK1C)型高血压大鼠的血压,MK-421是一种新的ACE抑制剂,化学名:N     

巯甲丙辅酸和硫酸镁佐治顽固性心衰

巯甲丙辅酸和硫酸镁佐治顽固性心衰０５０３００井陉县医院段群录我院于１９９１年２月～１９９３年６月，收治顽固性心衰４９例，其中２５例在常规方法治疗基础上，给予巯甲丙辅酸和硫酸镁治疗为观查组，２４例用常规方法治疗为对照组，经统计学处理，观查组疗效优于对照...     

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（ｃａｎｔｏｐｒｉｌ）对高血压肥大心肌缺血－丙灌注的影响,本实验以造成大鼠腹主动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大鼠肉体心脏缺血－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,而预先应用巯甲丙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,避免了钙在心肌内过多积聚。表明巯甲丙脯酸具有抗高血压肥大心肌缺血－再灌注损伤的作用。     

血管紧张素转化酶抑制剂简介

血管紧张素转化酶(ACE)抑制剂阻滞血管紧张素Ⅰ转化为Ⅱ,使循环中血管紧张素Ⅱ水平下降,是一类较为理想的血管扩张剂。在高血压和充血性心力衰竭(CHF) 治疗中的应用日益增多。作为抗高血压药时,降压效果显著,不影响血脂代谢;对于高血压伴有左室肥厚的患者,在血压控制后左室肥厚也隋之消退。CHF患者经ACE抑制剂治疗后,运动耐量增大;甲巯丙脯酸的优点是不损害脑循环,依纳普利则使室性心律失常明显减轻,猝死人数减少。     

福辛普利对非糖尿病高血压伴有胰岛素抵抗的影响

目的研究福辛普利对非糖尿病高血压伴有胰岛素抵抗的影响。方法福辛普利治疗非糖尿病高血压伴有胰岛素抵抗的患者46例,治疗前后测定基础血压、空腹血糖(FBG)、空腹胰岛素(FINS)水平,以稳态模型(Homamodel)公式计算胰岛素抵抗(IR),并行超声心动图检查。结果治疗后基础均值收缩压由治疗前的(178±49)mmHg,降至(130±40)mmHg;空腹胰岛素水平、胰岛素抵抗指数均较治疗前下降(P<0.05),室间隔厚度、左心室后壁厚度、左心室心肌重量和左心室重量指数均改善(P<0.05)。结论福辛普利对伴有胰岛素抵抗的高血压有良好的治疗作用。     

EFFECT OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS CAPTOPRIL AND ENALAPRIL ON cAMP CONTENT OF SPECIFIC BRAIN AREAS IN SPONTANEOUSLY HYPERTENSIVE RATS

1. The influence of two angiotensin-converting enzyme inhibitors, captopril and enalapril, on the cAMP content of microdissected brain areas was examined in spontaneously hypertensive rats. Both drugs depleted systolic arterial blood pressure significantly. 2. Captopril and enalapril increased the level of cAMP in catecholaminergic cell groups in the lower brain-stem. Captopril was more effective in the substantia nigra, while enalapril treatment resulted in high cAMP levels in the ventrolateral medulla oblongata (A1 catecholaminergic cell group). 3. Both drugs, especially captopril, depleted cAMP content in the cingulate cortex. 4. No changes in cAMP levels were measured in the primary baroreceptor centre (nucleus of the solitary tract) following either captopril or enalapril treatment.     

FAILURE OF CAPTOPRIL TO LOWER BLOOD PRESSURE IN SPONTANEOUSLY HYPERTENSIVE RATS OFFERED WATER AND SALINE TO DRINK

The hypotensive action of chronic oral captopril treatment (50 mg/kg per day) was examined in two groups of male spontaneously hypertensive rats (SHR) of the Okamoto strain, one group offered a choice of water and 0.9% saline as drinking fluid, the other offered water alone, a third group of SHR, offered a choice of water and 0.9% saline, were treated with vehicle (0.9% saline, 2 ml/kg per day). Captopril treatment, over ten days, significantly lowered blood pressure in the group drinking water only but failed to significantly alter the blood pressure of SHR drinking a choice of water and 0.9% saline. Vehicle treatment did not alter the blood pressure of SHR drinking a choice of saline and water. In an identical experiment using male, genetically hypertensive rats (GHR) of the Smirk strain, captopril lowered blood pressure to the same extent in GHR drinking either a choice of water and 0.9% saline or water alone. In conclusion, the reported exaggerated saline preference of the spontaneously hypertensive rat appears to antagonize the hypotensive action of captopril.     

ANGIOTENSIN CONVERTING ENZYME INHIBITOR, CAPTOPRIL, INHIBITS CARDIAC HYPERTROPHY WITHOUT CHANGING COLLAGEN TYPES AND CONCENTRATION IN SPONTANEOUSLY HYPERTENSIVE RATS

1. The effects of the ACE inhibitor, captopril, on collagen metabolism in spontaneously hypertensive rats (SHR) with cardiac hypertrophy was examined. Captopril (100 mg/kg per day) was administered in drinking water to 20 week old male SHR for 12 weeks. Collagen concentration was calculated from hydroxyproline content, and relative proportions of types I, III and V collagen were determined by non-interrupted SDS-polyacrylamide gel electrophoresis (SDS-PAGE). These parameters were examined in age and sex matched Wistar-Kyoto (WKY) rats, as well as in non-treated SHR, and compared with those of captopril-treated SHR. 2. Captopril significantly reduced both blood pressure (191 ± 12.1 vs 146 ± 11.2 mmHg, P < 0.01), and the ratio of left ventricular (LV) weight to bodyweight (BW; 2.38 ± 0.17 vs 2.05 ± 0.12 mg/g, P < 0.01). There were no significant differences in collagen concentration among WKY rats, captopril-treated SHR and non-treated 32 week old SHR. However, total collagen content in captopril-treated SHR reduced significantly compared with non-treated 32 week old SHR (16.8 ± 2.0 vs 21.3 ± 0.8 mg, P < 0.01). The relative proportion of type V collagen was significantly higher in both captopril-treated (58.6 ± 3.4 vs 46.8 ± 1.3%, P < 0.01) and non-treated 32 week old SHR (59.9 ± 3.1 vs 46.8 ± 1.3%, P < 0.01) compared with WKY rats. However, there were no significant differences between captopril-treated SHR and non-treated 32 week old SHR. 3. The data from this study showed that captopril reduced cardiac hypertrophy, as reported previously, but did not change collagen types and concentration of the hypertrophied myocardium in SHR.     

EFFECT OF DIETARY UREA ON BLOOD PRESSURE IN SPONTANEOUSLY HYPERTENSIVE RATS

The feeding of a normal diet containing 13.5% urea (in place of protein in a high protein diet) attenuated the development of severe hypertension and decreased the incidence of stroke in spontaneously hypertensive rats (SHR), when 1% NaCl solution was given to them. The urea not only increased urine volume, but also increased urinary sodium excretion in SHR given 1% NaCl for drinking. Although there was no obvious difference in erythrocyte size between the urea and the control groups, there was a significant inverse correlation between plasma urea level and erythrocyte size. These results suggest that a high protein diet reduced blood pressure partly through the diuretic effect of urea, the common metabolite of various proteins.     

EFFECTS OF CAPTOPRIL ON THE SLEEP EEG OF SPONTANEOUSLY HYPERTENSIVE RATS

Intracerebroventricular captopril produces significantly different effects on the sleep electroencephalogram (EEG) of normotensive Wistar-Kyoto (WK) and spontaneously hypertensive rats (SHR). The compound produces a definite pattern of decrease in the percentage and power of the lower frequency EEG of the SHR. Corresponding action on the WK was confined to a general decrease in the power of the EEG. These findings suggest that certain components of the central renin-angiotensin system in the SHR are abnormal.     

HYPOTENSIVE EFFECTS OF CAPTOPRIL ADMINISTERED CENTRALLY IN INTACT CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS AND PERIPHERALLY IN ANEPHRIC ANAESTHETIZED SPONTANEOUSLY HYPERTENSIVE RATS

1. The hypotensive response to captopril in anaesthetized spontaneously hypertensive rats (SHR) is not modified by bilateral nephrectomy performed 1 or 24 h previously. 2. Intracerebroventricular injection (i.c.v.) of captopril (2 mg kg^?1) significantly lowered blood pressure of conscious SHR over a 7-h period of observation but there was no significant blood pressure response to i.c.v. vehicle, or to intravenous captopril (2 mg kg^?1) in SHR. 3. There was no significant blood pressure response to captopril (2 mg kg”') i.c.v. in the normotensive Wistar Kyoto controls (NT-WK). 4. These results indicate that captopril can lower the blood pressure of SHR by mechanisms independent of the kidneys or the circulating renin-angiotensin system. 5. The hypotensive effect of central captopril in SHR but not in the NT-WK suggests biochemical differences between the brains of the two rat strains.     

EFFECTS OF CENTRAL SEROTONIN NERVE LESIONS ON BLOOD PRESSURE IN NORMOTENSIVE AND HYPERTENSIVE RATS

1 Separate ascending and descending pathways of serotonin (5-hy-droxytryptamine, 5-HT) nerves in the rat central nervous system have been selectively lesioned by Idealized intracerebral administration of 5,7-dihydroxytryptamine (5,7-DHT) after pretreatment with desipramine (DMI). 2 Bilateral injections of 5,7-DHT into the medial forebrain bundle or the cervical spinal cord caused extensive losses of 5-HT and tryptophan hydroxylase in the anterior hypothalamus and thoracic spinal cord, respectively, without affecting noradrenaline (NA) levels. 3 The hypothalamic lesions caused only a slight, transient reduction of systolic blood pressure in normotensive rats. 4 A more pronounced and sustained hypotension occurred in normotensive rats but not in hypertensive rats after the spinal lesions.     

前胡丙素对高血压大鼠血压及犬血管阻力的影响

目的　观察前胡丙素(pra C)的降压及对外周血管阻力的影响。方法　在肾型高血压大鼠模型与正常血压大鼠用尾容积法测血压。用RDB III型输液泵连接于麻醉杂种犬,以控制血流量与压力法直接测定锥动脉、冠脉左旋支、股动脉的阻力。结果　pra-C 20 mg·kg^-1·d^-1 ig给药3 0d对肾性高血压大鼠(RHR)降压峰值时间为6h ,从(213±10 )mmHg降至(144.0±1.5)mmHg,降低原水平30% ,持续至20h。pra-C分别以100 μg·kg^-1 及20 μg·kg^-1与pra-E 20 μg·kg^-1iv可降低上述血管的阻力,减慢心率,降低阻力呈剂量相关。结论　pra-C有降压作用,降低犬外周动脉阻力,增加小鼠耐缺氧时间。     

ANGIOTENSIN CONVERTING ENZYME IN THE BRAIN OF SPONTANEOUSLY HYPERTENSIVE RATS

1. Angiotensin converting enzyme (ACE) was measured in homogenates of regions of rat brain using the substrate Hip-His-Leu. 2. The enzyme resembled classical ACE in its marked CI” dependence and inhibition by both SQ 20,881 (25 μmol/1) and EDTA (1 mmol/1). 3. Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto controls (NT-WK) were killed at 20-22 weeks of age and their brains dissected into eight regions. 4. There were marked region variations of ACE with highest levels in striatum, hippocampus, cerebellum and pituitary and lower levels in hypothalamus and cerebral cortex. 5. In three brain regions ACE was significantly lower in SHR compared to NT-WK: medulla oblongata (P<0.05), hypothalamus (P<0-02) and cerebral cortex (P < 005). In the other sites the levels were not different. 6. These region-specific differences of ACE in the SHR could lead to altered production or metabolism of central neuropeptides postulated to be involved in the control of blood pressure.