卡托普利早期治疗自发性高血压大鼠阻止遗传性高血压形成的机理

本文探讨早期卡托普利治疗阻止高血压形成的机制。自发性高血压大鼠（ＳＨＲ）宫内期给药（１００ｍｇ·ｋｇ－１·ｄ－１）到１６周龄，４０ｗｋ处死。测定收缩压，血管壁／腔面积比（Ｍ／Ｌ），血管收缩（后肢灌注Ｆｏｌｋｏｗ模型）和舒张（动脉环体外实验）功能。卡托普利治疗显著降低血压，停药后２４ｗｋ，血压仍维持在相对低的水平（２１．１±１．１ｋＰａ，对照２８．５±１．１ｋＰａ。Ｐ＜０．０１）．治疗能明显减少Ｍ／Ｌ并接近正常ＷＫＹ大鼠水平。治疗组ＳＨＲ大鼠主动脉对硝普钠舒张敏感性及最大舒张反应明显比８ＨＲ增高，后肢阻力血管苯福林灌注显示ＳＨＲ最小灌注压，最大灌注压，曲线最大斜率都明显比ＷＫＹ大，ＥＣ５０明显较小，治疗的ＳＨＲ以上四个指标几乎达到与ＷＫＹ相同水平。结论：卡托普利持久地阻止高血压形成，持久降压的机理可能是在抑制血管肥厚基础上，减弱末梢血管阻力，改善血管舒张功能。关键词     

卡托普利对老年肺心病患者肺血流动力学的影响

对肺心病缓解期患１５例给予卡托普利２５ｍｇ，ｔｉｄ，ｐｏ，共１０ｄ。对照组２０例给予维生素Ｂ１与谷维素各１０ｍｇ，ｔｉｄ，ｐｏ，共１０ｄ。治疗前后比较２组肺血流动力学。结果：卡托普利组肺动脉平均压由３．６±ｓ０．３ｋＰａ降至２．６±０．９ｋＰａ，肺血管阻力由２３±８ｋＰａ／（ｓ．Ｌ）降至１８±７ｋＰａ／（ｓ．Ｌ），心脏指数由２．２±０．６Ｌ／（ｍｉｎ．ｍ＾２）上升至２．８±０．９Ｌ／（ｍｉｎ．ｍ     

卡托普利对老年肺心病患者肺血流动力学的影响

对肺心病缓解期患者１５例给予卡托普利２５ｍｇ，ｔｉｄ，ｐｏ，共１０ｄ。对照组２０例给予维生素Ｂ１与谷维素各１０ｍｇ，ｔｉｄ，ｐｏ，共１０ｄ。治疗前后比较２组肺血流动力学。结果：卡托普利组肺动脉平均压由３．６±ｓ０．３ｋＰａ降至２．６±０．９ｋＰａ，肺血管阻力由２３±８ｋＰａ／（ｓ·Ｌ）降至１８±７ｋＰａ／（ｓ·Ｌ），心脏指数由２．２±０．６Ｌ／（ｍｉｎ·ｍ２）上升至２．８±０．９Ｌ／（ｍｉｎ·ｍ２），Ｐ值均＜０．０５。对照组无上述作用，组间比较，Ｐ值均＜０．０５。     

拉西地平治疗糖尿病并发高血压及单纯高血压的疗效

目的：观察拉西地平对糖尿病并发高血压和单纯高血压的治疗效果。方法：单纯高血压和糖尿病并发高血压各２５例,服安慰剂 ２ ｗｋ后服用拉西地平２ ｍｇ,如血压未降至正常,则渐增到４,６ ｍｇ或 ８ ｍｇ,ｐｏ, ｑｍ, ｐｃ,共 ６ ｗｋ。结果： ２组治疗 ２ｗｋ后收缩压分别下降达（３．４±０．６）ｋＰａ或（３．５±０．６）ｋＰａ,（Ｐ＜０．０１）;舒张压分别下降达（２．０±０． ３） ｋＰａ或（２． ２± ０． ４） ｋＰａ（ Ｐ＜ ０． ０５）。治疗 ４ ｗｋ及６ｗｋ,均显示收缩压进一步下降;舒张压均维持原疗效;治疗６ｗｋ期间对心率、血糖、血脂均无显著影响。结论：拉西地平治疗单纯性或糖尿病并发高血压均有较好疗效。     

西拉普利与依那普利治疗原发性高血压的比较

原发性高血压４１例，其中２１例（男性１２例，女性９例；年龄５４±ｓ８ａ采用西拉普利平均每天口服３．６±１．３ｍｇ，共４ｗｋ。另２０例（男性６例，女性１４例；年龄５４±７ａ）采用依那普利平均每天口服１１±３ｍｇ，共４ｗｋ。结果：２组均于１ｗｋ即开始有显降压作用，随疗程增加，疗效日益显（Ｐ＜０．０１）。下降幅度２组间相似（Ｐ＞０．０５）。西拉普利尚有对体重及血清钠，氯减低的作用，且无明显不良反应。     

自发性高血压大鼠血小板神经肽Y释放增多

比较自发性高血压大鼠（ＳＨＲ）和ＷＫＲ大鼠血浆和血小板中神经肽Ｙ（ＮＰＹ）的含量，以及ＡＤＰ、凝血酶和胶原引起血小板聚集和ＮＰＹ释放的差别。方法：应用放射免疫分析法测定血小板及血浆ＮＰＹ听含量。结果：ＳＨＲ和ＷＫＲ大鼠血浆ＮＰＹ含量无明显差别，分别为２．１±１．０和１．８±１．０μｇ．Ｌ＾－１，而ＳＨＲ血小板ＮＰＹ含量（３２±６μｇ．Ｌ＾－１）显高于ＷＫＹ大鼠（２２±９μｇ．Ｌ＾－１）。凝血酶和     

普伐他汀用序贯设计及期中分析法治疗高脂血症

目的：了解普伐他汀降血脂疗效。方法：用最小序贯设计及期中分析法将１０２例ＩＩａ,ＩＩｂ型高脂血症病人采用双盲法分为普伐他汀组５３例,给普代他汀 １０ ｍｇ,ｐｏ, ｑｎ×８ ｗｋ;对照组 ４９例,给服外观相同的淀粉片,服法疗程相同。结果：治疗４ｗｋ与 ８ ｗｋ普伐他汀组ＴＣ下降差值分别为（１．７±０．８）ｍｍｏｌ·Ｌ－１与（２．６±０．９）ｍｍｏｌ·Ｌ－１;ＴＧ下降差值为（０．６±０．６）ｍｍｏｌ·Ｌ－１与（１．０±０．５）ｍｍｏｌ·Ｌ－１,治疗８ｗｋ后ＴＣ,ＴＧ下降差值２组组问比较Ｐ＜０．０１;普伐他汀组治疗２ ｗｋ开始ＨＤ Ｌ－Ｃ开始升高（ Ｐ＜ ０． ０５）,对照组治疗 ２～ ８ ｗｋ均未见显著升高。结论：普伐他汀组有显著降低ＴＣ,ＴＧ及升高ＨＤＬＣ作用。     

美西律抑制频发室性早搏的疗效及其对心率变异的影响

目的：评价美西律治疗频发室性早搏（ 简称室早） 的疗效及其对心率变异（ＨＲＶ） 的影响。方法：２４ ｈ 动态心电图记录室早＞ ５ 次／ｍｉｎ 的病人３１例,男性１４ 例,女性１７ 例,年龄（４２ ±ｓ １６） ａ,用美西律０ ．１ ～０ ．２ ｇ , ｐｏ,ｔｉｄ, 疗程２ ｗｋ 以上。治疗后复查动态心电图,观察室早和ＨＲＶ 的变化。结果：治疗前后２４ ｈ 室早的自然对数分别为（８ ．９ ±０ ．９）次和（６ ±３） 次,下降（２ ．５ ±２ ．９） 次（ Ｐ＜ ０ ．０１） , 成对室早对数由（２ ．１ ±２ ．３） 次下降至（１ ．０ ±１ ．９） 次（ Ｐ＜ ０ ．０１） ,２４ ｈ 室性心动过速的对数由（ ０ ．９ ±１ ．６） 次降至（０ ．４ ±１ ．１） 次（ Ｐ＜ ０ ．０１） 。但５ 个ＨＲＶ 时域指标在治疗前后无明显变化。结论：美西律对室性早搏有显著的抑制作用,未发现其对心率变异时域指标有明显影响。     

卡托普利对血管平滑肌细胞结构和钙的影响

为调查卡托普利（Ｃａｐ）的特殊血管效应和探讨其机制，用电镜和图象技术观察口服Ｃａｐ对自发性高血压大鼠（ＳＨＲ）主动脉平滑肌细胞（ＡＳＭＣ）超微结构和Ｃａ２＋的影响。用Ｃａｐ治疗ＳＨＲ１６ｗｋ，降低主动脉中膜厚度（１０４．７±６．６μｍｖｓ１３５．７±８．１μｍ）和改善ＡＳＭＣ的异常超微结构征象如异形核、线粒体肿胀和管状结构扩张以及降低ＡＳＭＣＣａ２＋浓度。故Ｃａｐ有阻止ＳＨＲ主动脉中膜肥厚和改善ＳＨＲＡＳＭＣ异常性超微结构的特殊血管效应。而降ＡＳＭＣＣａ２＋可能部分与它的特殊效应有关。     

细胞外钙离子对培养大鼠交感神经元烟碱受体失敏的影响

以培养的新生大鼠颈上交感节神经元为标本，使用膜片钳全细胞记录技术，观察了细胞外Ｃａ２＋对烟碱受体失敏的影响．发现向神经元喷射１００μｍｏｌ·Ｌ－１ＡＣｈ，可即刻诱发迅速上升的内向电流（ＡＣｈ电流）．随着胞外Ｃａ２＋浓度的上升，ＡＣｈ电流衰减明显加快（Ｐ＜０．０１）．而ＡＣｈ诱发电流的幅度和上升速率则随胞外Ｃａ２＋浓度的上升而显著增加（Ｐ＜０．０１）．当胞外Ｃａ２＋为０，２和６ｍｍｏｌ·Ｌ－１时，ＡＣｈ电流衰减的时间常数分别为８．０±４．３ｓ（ｎ＝９），４．２±０．９ｓ（ｎ＝８）和２．６±０．７ｓ（ｎ＝８）．诱发电流的幅度（ｎＡ）分别为２．０±０．９（ｎ＝９），３．３±１．０（ｎ＝８）和５．１±１．６（ｎ＝８）．其上升速率（ｐＡ／ｍｓ）分别为２．６±０．８和９．３±１．６（ｎ＝８）．以上结果说明，胞外Ｃａ２＋浓度的增加，可加速ＡＣｈ电流的衰减，即加速烟碱受体的失敏，同时提高ＡＣｈ电流幅度，加快烟碱受体离子孔道的开放速率．提示交感神经元烟碱受体上可能存在着不同的Ｃａ２＋结合位点．通过对这些不同位点的作用，Ｃａ２＋可以从两方面影响烟碱受体的功能，进而调制胆碱能神经元的突触传递效率．     

Binding of [3H]nitrendipine to cardiac and cerebral membranes from normotensive and renal, deoxycorticosterone/NaCl and spontaneously hypertensive rats

The properties of [3H]nitrendipine binding to cardiac and cerebral membranes from normotensive Wistar-Kyoto (WKY) and renal (RHR), deoxycorticosterone/NaCl (DOCA-HR) and spontaneously hypertensive (SHR) rats were investigated. The maximal numbers of binding sites (Bmax) in the striatum, thalamus and hippocampus for SHR increased by 21.4-40.0, 28.1-40.4 and 21.4-34.1% of the numbers in WKY, but the apparent dissociation constants (KD) in the cerebral membranes differed very little between WKY and SHR. In the cardiac membranes, KD and Bmax values differed very little between WKY and SHR. In the RHR and DOCA-HR, the Bmax values in the striatum, thalamus and hippocampus were similar to those of WKY. These findings suggest that the increase in Bmax of [3H]nitrendipine in the striatum, thalamus and hippocampus of SHR may play a part in the development and maintenance of high blood pressure in SHR.     

The symptoms of unilateral inflammation in spontaneously hypertensive,renal hypertensive and normotensive wistar kyoto and wistar rats

Widy-Tyszkiewicz E, Kohutnicka M, Mierzejewski P, Czlonkowski A. The symptoms of unilateral inflammation in spontaneously hypertensive, renal hypertensive and normotensive Wistar Kyoto and Wistar rats. Inflammopharmacology. 1994;2:337-343. Spontaneously hypertensive (SHR) and renal hypertensive (RHR), Wistar (NR) and Sham or Wistar Kyoto (WKY) rats were tested for clinical symptoms following inoculation with Freund’s adjuvant in the unilateral hind paw. In the present study, body weight change (during weeks 1–11) was examined once a week and inflammatory score of hindpaw twice a week. The body weight gain was increased in the WKY compared with NR/Sham, SHR and RHR groups. Inflammatory changes were also most profoundly exhibited in the NR/Sham, the SHR and the RHR, compared with the WKY rats. The data may reflect a genetic difference not necessarily related to elevated blood pressure.     

Antihypertensive effect of naftopidil (KT-611), a novel alpha 1-adrenoceptor antagonist, in freely moving experimental hypertensive rats and dogs

The antihypertensive effect of naftopidil (KT-611) following single oral administration was investigated in normotensive Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR), DOCA-Salt hypertensive rats (DHR), 2-kidney 1-clip renal hypertensive rats (RHR) and Grollman type renal hypertensive dogs with 1-kidney (RHD); and it was compared with that of the selective alpha 1-adrenoceptor antagonist prazosin. The blood pressure and heart rate were measured under the unanesthetized, unrestrained state through an arterial catheter that was chronically implanted into the abdominal aorta. In SHR and WKY, both KT-611 (10 and 30 mg/kg, p.o.) and prazosin (1 and 3 mg/kg, p.o.) markedly inhibited the pressor response to the alpha 1-adrenoceptor agonist phenylephrine (3 micrograms/kg, i.v.). KT-611 (10 to 100 mg/kg, p.o.) showed a dose-dependent hypotensive effect in SHR, DHR and RHR but not in WKY. The hypotensive effect of KT-611 reached maximum at 0.5-1 hr, lasted for 4-6 hr and was more potent in DHR and RHR than in SHR. The potency of KT-611 was 1/10-1/30 weaker than that of prazosin. In RHD, single oral administration of KT-611 (1 to 10 mg/kg) caused a dose-dependent and long-lasting hypotensive effect. These results suggest that KT-611 has a long-lasting hypotensive effect in experimental hypertensive animal models.     

Nitric oxide-dependent hypotensive effects of adrenomedullin in rats

The association of nitric oxide (NO) with the hypotensive effects of adrenomedullin (AM) was investigated in anesthetized rats. Spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were used at 11–13 weeks of age. Blood pressure and heart rate were measured from the femoral artery under mild anesthesia using pentobarbital. AM, over the dose range of 0.3–3 nmol/kg iv, produced dose-dependent sustained hypotension and compensatory tachycardia. These effects of AM at 0.3, 1, and 3 nmol/kg iv were significantly stronger in SHR (−9 ±4, −53 ±9, and −62 ±7 mmHg) than in WKY (−4 ±1, −16 ±2, and −22 ±2 mmHg). Those at 1 nmol/kg iv were markedly inhibited in SHR (−53 to −19 mmHg) and in WKY (−16 to −12 mmHg) by treatment with the nitric oxide synthase (NOS) inhibitor N^G-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg iv). On the other hand, the difference of hypotensive effects in WKY and SHR by calcitonin gene-related peptide (CGRP) and the inhibitory effect by the treatment with L-NAME were smaller than seen with AM. These effects of CGRP at 0.03, 0.1, 0.3, and 1 nmol/kg iv were in SHR (−7 ±2, −18 ±3, −42 ±4, and −74 ±3 mmHg) and in WKY (−7 ±1, −16 ±1, −26 ±3, and −41 ±2 mmHg), respectively. Those at 0.3 nmol/kg iv were not significantly inhibited in SHR (−42 to −43 mmHg) and in WKY (−26 to −20 mmHg) by treatment with L-NAME, 10 mg/kg iv. These results indicate that the AM hypotensive effect was more pronounced in the hypertensive state and strongly depends on NO synthesis. © 1996 Wiley-Liss, Inc.     

Effect of γ-aminobutyric acid and nattokinase-enriched fermented beans on the blood pressure of spontaneously hypertensive and normotensive Wistar–Kyoto rats

In this study we have evaluated the changes in arterial blood pressure in spontaneously hypertensive rats (SHR) caused by the short-term intake of Bacillus subtilis B060-fermented beans with significant γ-aminobutyric acid (GABA) and nattokinase activity. After being weaned, 7-week-old male SHR and 7-week-old male Wistar–Kyoto (WKY) rats were randomized into seven groups. Until the 8^th week of life, the rats in each group were given one of the following: Group 1, high dose of GABA and nattokinase in the SHR (SHD); Group 2, medium dose of GABA and nattokinase in the SHR (SMD); Group 3, low dose of GABA and nattokinase in the SHR (SLD); Group 4, negative control in the SHR (SD); Group 5, positive control in the SHR (SM); Group 6, high dose of GABA and nattokinase in the WKY (WHD); and Group 7, negative control in the WKY (WD). Distilled water served as the negative control, and captopril (50 mg/kg), a known ACE inhibitor, served as the positive control. Systolic blood pressure and diastolic blood pressure values were measured weekly from the 8^th week to the 16^th week of life using the tail-cuff method. A definite decrease in systolic and diastolic blood pressure values could be observed in the rats treated with captopril and in the rats that received GABA and nattokinase. The greatest antihypertensive effect was observed when the pharmacological treatment was administered. The effect of the daily intake of fermented beans containing GABA and nattokinase may be helpful in controlling blood pressure levels in hypertensive model animals. The fermentation of beans with B. subtilis B060 may therefore constitute a successful strategy for producing a functional food with antihypertensive activity.     

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 γ-aminobutyric acid and nattokinase-enriched fermented beans on the blood pressure of spontaneously hypertensive and normotensive Wistar–Kyoto rats

In this study we have evaluated the changes in arterial blood pressure in spontaneously hypertensive rats (SHR) caused by the short-term intake of Bacillus subtilis B060-fermented beans with significant γ-aminobutyric acid (GABA) and nattokinase activity. After being weaned, 7-week-old male SHR and 7-week-old male Wistar–Kyoto (WKY) rats were randomized into seven groups. Until the 8^th week of life, the rats in each group were given one of the following: Group 1, high dose of GABA and nattokinase in the SHR (SHD); Group 2, medium dose of GABA and nattokinase in the SHR (SMD); Group 3, low dose of GABA and nattokinase in the SHR (SLD); Group 4, negative control in the SHR (SD); Group 5, positive control in the SHR (SM); Group 6, high dose of GABA and nattokinase in the WKY (WHD); and Group 7, negative control in the WKY (WD). Distilled water served as the negative control, and captopril (50 mg/kg), a known ACE inhibitor, served as the positive control. Systolic blood pressure and diastolic blood pressure values were measured weekly from the 8^th week to the 16^th week of life using the tail-cuff method. A definite decrease in systolic and diastolic blood pressure values could be observed in the rats treated with captopril and in the rats that received GABA and nattokinase. The greatest antihypertensive effect was observed when the pharmacological treatment was administered. The effect of the daily intake of fermented beans containing GABA and nattokinase may be helpful in controlling blood pressure levels in hypertensive model animals. The fermentation of beans with B. subtilis B060 may therefore constitute a successful strategy for producing a functional food with antihypertensive activity.     

Enhanced thromboxane A2 biosynthesis in the kidney of spontaneously hypertensive rats during development of hypertension

Arachidonic acid (AA)-induced pressor response and production of thromboxane YXB₂, the stable metabolite of TXA₂, prostaglandin (PG)-like substance (PLS) and 6-keto-PGF_1α the stable metabolite of prostacyclin (PGI₂), were studied using isolated, perfused kidneys of 6- and 18-week old spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), two-kidney, one clip hpertensive rats (RHR) and DOCA/salt hypertensive rats (DOCA/salt HR). The AA-induced pressor response and release of TXB₂ were highest in the 6-week old SHR, whereas, the release of PLS and 6-keto-PGF_1α was marked in the 18-week old SHR and the established hypertensive stages of both RHR and DOCA/salt HR. In the kidneys of SHR and WKY, exogenous TXA₂ induced a severe vasoconstriction and there was a positive correlation between the AA-induced pressor response and the release of TXB₂ or PLS. Thus, the initiation of hypertension in SHR may follow an accelerated synthesis of TXA₂ against PGI₂ in response to stimuli which induce a release of AA.     

几种降压药对自发性高血压大鼠微循环的影响

在自发性高血压大鼠中进行实验，将动物分为三组，分别以氨酰心安，疏甲丙脯氨酸及吲达帕胺治疗。另取一组未经治疗的ＳＨＲ和一组正常血压的ＷＫＹ大鼠作对照。实验１２周后检查，所有降压药治疗的三组ＳＨＲ，血压均降到正常范围；但是睾２肌微循环却显示不高的变化。