动态血压监测观察苯那普利的降压疗效

目的观察苯那普利的降压效果及对肝、肾功能的影响。方法４４例高血压患者用药前进行２４ｈ动态血压监测，并检查肝、肾功能及血糖，然后口服苯那普利１０～２０ｍｇ／ｄ，４周后再行动态血压监测并复查肝、肾功能及血糖，比较治疗前后各项指标的变化。结果Ⅰ、Ⅱ期高血压患者血压呈白天高、夜间低的变化规律；Ⅲ期患者舒张压失去昼夜变化规律；苯那普利对昼夜血压均显示良好的降压效果，对肝、肾功能无不良影响。结论苯那普利具有良好的降压效果，对肝肾功能及血糖无不良影响。     

寒冷应激和高盐饮食复合环境因素对大鼠血压的影响

目的　应用寒冷刺激及高盐饮食复制大鼠高血压模型 ,探讨环境因素在高血压发病中的作用。方法　 10 0只3月龄的雄性大鼠 ,随机分成 4组 :1.寒冷组 (n =2 8) ,动物置于 4± 2℃的冷环境 ,每天 4小时 ;2 .高盐组 (n =2 8) ,每天给予 8%的盐饲料 ;3.复合组 (n =2 8) ,动物在暴露于冷环境的基础上每天还给予 8%的高盐饮食 ;4.正常对照组 (n=16 ) ,不给任何刺激因素。四组总的实验时间为 8周。每周测一次尾压、心率。结果　第一周末 ,寒冷、高盐、复合组的尾压、心率比对照组均明显升高 (P· <0 0 1) ,三周末血压达到最高 ,分别为 (12 7.0± 6 .0 ,12 5 .9± 5 .5 ,131± 6 .0 )mmHg。 结论　应用复合环境因素成功地复制了大鼠高血压模型 ;环境因素对血压有明显影响。     

不同人群降压目标值的探讨

高血压是严重威胁人类健康的疾病,同时作为心脑血管疾病的高危因素,高血压患者往往合并有一种或多种慢性疾病,由此引起的病死率已升至所有疾病病死率的首位,因此合理的控制血压显得至关重要。近来,关于高血压人群降压目标值的问题引起广泛争议,现将对缺血性心脏病患者、糖尿病患者、脑血管疾病患者、慢性肾病患者和老年人高血压的降压目标值做一综述。     

下丘脑内血管升压素在紧张应激引起大鼠血压升高反应中的作用

目的观察下丘脑血管升压素（ｖａｓｏｐｒｅｓｓｉｎ,ＡＶＰ）在慢性紧张应激引起大鼠血压升高过程中的作用。方法实验在给予慢性应激刺激后,引起动物血压出现显著升高的雄性Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ大鼠中进行。在通过侧脑室（ｉｃｖ．）及外周静脉（ｉｖ．）给予大鼠注射血管升压素Ｖ１受体拮抗剂ｄ（ＣＨ２）５Ｔｙｒ（Ｍｅ）ＡＶＰ后,观察其对动物平均动脉压（ＭＢＰ）的影响。结果在正常大鼠中ｉｃｖ．或ｉｖ．注射ｄ（ＣＨ２）５Ｔｙｒ（Ｍｅ）ＡＶＰ后,动物ＭＢＰ无显著改变,但在慢性应激引起血压出现显著升高的大鼠中,ｉｃｖ．ｄ（ＣＨ２）５Ｔｙｒ（Ｍｅ）ＡＶＰ后,动物血压出现显著降低,降压反应持续约２ｈ,最大效应出现在给药后约４５ｍｉｎ,大鼠ＭＢＰ从给药前的１３４±１１．９ｍｍＨｇ的基础上,平均下降３５．６±１２．６ｍｍＨｇ,而通过ｉｖ．ｄ（ＣＨ２）５Ｔｙｒ（Ｍｅ）ＡＶＰ后,却未观察到ＭＢＰ有显著改变。结论由下丘脑合成并释放的ＡＶＰ参与慢性应激引起的大鼠血压升高反应,其作用可能主要通过中枢Ｖ１受体实现     

Psychosocial Stress Elevates Blood Pressure Via an Opioid Dependent Mechanism in Normotensive Rats

Stress is an important risk factor in cardiovascular diseases, including hypertension. Endogenous opioids are known to be elevated in stress and in various models of hypertension with differing etiologies. Blockade of endogenous opioids with naloxone has been demonstrated to attenuate or reverse the elevation in blood pressure in both renovascular and spontaneous hypertension. In the current study, increased blood pressure was induced using a model of psychosocial stress. During the first week of stress, systolic blood pressure rose rapidly to reach a level that was sustained throughout the remaining period of stress. Chronic infusion of the opiate antagonist, naloxone, both prevented and completely reversed the elevated blood pressure due to psychosocial stress. These data demonstrate that elevated endogenous opioids are important factors in cardiovascular regulation and are likely to influence both the development and maintenance of stress-induced hypertension.     

Depletion of Resistance Vessel Polyamines Attenuates Angiotensin II Induced Blood Pressure Rise in Rats

Vascular structural changes in hypertension are proposed to contribute to raised peripheral resistance. Endogenous polyamines (putrescine, spermidine and spermine) have an essential role in cellular growth and may be required in vascular restructuring. We have previously shown raised polyamines in resistance vessels in response to angiotensin I1 (angII) infusion in the rat and here we examined whether polyamine depletion influences the hypertensive process. Wistar-Kyoto rats were infused with either angII or saline by osmotic minipump, and maintained on either 2% difluoromethylornithine (DFMO; polyamine synthesis inhibitor) or water for 12days. AngII significantly increased tail-cuff blood pressure (bp), resistance vessel spermidine and spermine concentration, and media:lumen ratios. DFMO attenuated both the rse in bp (p<0.05) and vascular spermidine (p<0.05) in the angII infused rats but vascular structure was apparently unaffected on day 12. In conclusion, raised concentration of resistance vessel spermidine may be a necessary component of the ang II pressor effect.     

动态血压监测分析缓释维拉帕米和培哚普利的降压特点

采用3种血压测量方法［偶测血压（CBP），自测血压（SMBP），动态血压（ABPM）］对两组高血压病人进行2种缓释降压药比较（A组，缓释维拉帕米n=20；B组，培哚普利n=20）。结果提示，（1）治疗前，CBP与SMBP方法对血压的判断无差异，与ABPM方法比较有差别，治疗后，血压下降用3种方法比较，ABPM测量方法能明显区别夜间及白天血压变化，而CBP及SMBP方法则否。（2）用ABPM方法监测降压药物的效果，发现B组降低DBP强于A组，对SBP的降压两组药差异无显著性。     

Increased Collagen Synthesis in Blood Vessels of Hypertensive Rats and Its Reversal by Antihypertensive Agents

Collagen synthesis is increased in the aortas, mesenteric arteries, and to a lesser extent, in the hearts of rats either made hypertensive with desoxycorticosterone acetate-salt or that are spontaneously hypertensive. Several markers of collagen biosynthesis were shown to be increased, including prolyl hydroxylase (EC 1.14.11.2; proline, 2-oxoglutarate dioxygenase), prolyl hydroxylase-related antigen, total collagen content, and the incorporation of [(3)H]proline into total protein and into collagen. The antihypertensive agents chlorothiazide and reserpine, when administered before the onset of hypertension in the rats treated with desoxycorticosterone acetate-salt, prevented or diminished the increase in collagen biosynthesis. When reserpine was given after the onset of hypertension, prolyl hydroxylase activity was decreased concomitant with the decrease in blood pressure. Treatment with reserpine is particularly effective in diminishing arterial prolyl hydroxylase activity.     

应用动态血压监测评价氯沙坦治疗原发性高血压的降压疗效

目的：应用动态血压监测（ＡＢＰＭ）评估氯沙坦（ｌｏｓａｒｔａｎ）５０～１００ ｍｇ,每日１次,对轻、中度原发性高血压（ＥＨ）患者的２４小时降压效果。 方法：轻、中度ＥＨ患者 ３３例,服用 ２周安慰剂,坐位舒张压仍在 ９５～１１４ ｍｍＨｇ（１ ｍｍＨｇ＝０．１３３ ｋＰａ）者予氯沙坦５０ ｍｇ／ｄ,服药 ２周末血压下降未达有效标准者氯沙坦增加至 １００ ｍｇ／ｄ,氯沙坦治疗疗程共 ６周。于服安慰剂末及治疗２、４、６周末测诊室血压,于服安慰剂末及治疗６周末应用ＡＢＰＭ。 结果;氯沙坦治疗６周,降压总有效率为８７．５％;２４小时各时点血压均较治疗前显著下降（Ｐ＜０．０５、Ｐ＜０．０１）,不伴有心率及血压昼夜节律的改变;降低收缩压和舒张压的谷／峰值分别为５２．９％和６３．６％。能明显降低血尿酸（Ｐ＜０．０５）。除１例因头晕中途退出研究外,余不良反应轻微。 结论：氯沙坦 ５０～１００ ｍｇ,每日１次能平稳、有效地控制 ＥＨ患者 ２４小时血压,且患者总体耐受良好。     

Clonidine Antagonizes Pressor Effect of N-Methyl-D-Aspartate in the Rostral Ventrolateral Medulla of Rats

The purpose of the present study was to investigate the modulatory actions of adrenoreceptor agonists on N-methyl-D-aspartate (NMDA)-induced pressor effect in rostral ventrolateral medulla (RVLM). These drugs were locally applied into RVLM of urethane-anesthetized Sprague-Dawley rats through multibarrel pipettes. Microinjection of NMDA increased the arterial pressure, an effect which was abolished by pretreatment with clonidine, whereas neither the β-adrenergic agonist isoproterenol nor the α₁-adrenergic agonist phenylephrine did alter this pressor response. Previous experiments demonstrated that clonidine binds to noradrenergic α₂ and imidazoline receptors in the RVLM. Norepinephrine, which has high affinity for the α₂ receptor and low affinity to the imidazoline receptor, partially antagonized NMDA-induced hypertension. On the other hand, administration of selective imidazoline receptor antagonist idazoxan partially reversed clonidine-mediated antagonism of NMDA. Taken together, these results suggest that clonidine may modulate the excitatory amino acid -induced pressor response through noradrenergic α₂ and imidazoline receptors in the RVLM.     

Blood Pressure and Metabolic Effect of a Combination of Lercanidipine with Different Antihypertensive Drugs in Clinical Practice

The aim of this study is to assess the blood pressure (BP) and metabolic effects of lercanidipine when combined with other classes of first-line antihypertensive drugs in day-to-day clinical practice. For this study, we consecutively enrolled 162 patients with uncomplicated primary hypertension, who are partial responders to the treatment with lercanidipine over a period of 24 months. Patients were then allocated to the combination of lercanidipine (10–20 mg/day) with β-blockers, diuretics, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor blockers according to compelling indications (if any) and/or suggestions of European Society of Hypertension–European Society of Cardiology (ESH–ESC) guidelines. All the enrolled patients completed the study and no adverse drug reaction was registered during the research period. The association of a second drug with lercanidipine determined an additional BP decrease of either systolic BP or diastolic BP independently from the type of drug added (P always <.05). The additional effect of lercanidipine appears widely distributed with no significant differences in the size of BP decrease. From the metabolic point of view, the addition of a second drug did not determine a significant variation in the serum levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (P always >.05). Conversely, a significant decrease in fasting plasma glucose and serum levels of triglycerides has been observed in patients where lercanidipine has been combined with an angiotensin-converting enzyme inhibitor or an angiotensin-II receptor blocker. In conclusion, in our study we observed that lercanidipine-based protocols are well tolerated and efficacious in reducing BP. Moreover, the association of lercanidipine with renin–angiotensin system blockers is also associated with significant improvements in triglycerides and fasting plasma glucose.     

动态血压监测评价贝尼地平治疗原发性高血压的疗效观察

目的　应用动态血压监测 (ABPM )的方法评价贝尼地平治疗原发性高血压的降压疗效、谷 /峰比值及不良反应。方法　采用开放的方法 ,2 0例研究对象经 2周洗脱期 ,服用贝尼地平 4mg/d一次 ,2周末坐位舒张压 (SeDBP)≥ 90mmHg者加量至贝尼地平 8mg/d一次 ,继续服用 6周。于洗脱期末及治疗 8周末各行ABPM和实验室检查一次。结果　ABPM显示 8周末 2 4h、日间、夜间收缩压 (SBP/DBP)较洗脱期末分别下降 (9.4± 5 .4 / 6 .2± 4 .1)mmHg、(10 7± 6 .7/ 6 8± 3 8)mmHg、(6 9± 9 0 / 5 1± 7 7)mmHg。降压T/P值SBP为 5 8% ,DBP为 5 9%。无严重不良反应。 结论　贝尼地平 4～ 8mg/d一次为疗效确切的降压药物。     

Effect of Hydralazine on Serial Measurements of Exchangeable Sodium and Blood Pressure in Spontaneously Hypertensive Rats

Hydralazine was dissolved in 0.5% drinking saline (40 mg/1000 ml) labelled with isotope ²²Na and given to spontaneously hypertensive rats for four weeks. Another group of rats were given isotope labelled saline only and served as control. Measurements of total exchangeable sodium, blood pressure, pulse rate and weight were performed before and repeatedly during treatment. Before treatment exchangeable sodium, blood pressure, pulse rate, and weight were no different between the groups. The antihypertensive effect of hydralazine was marked and maintained throughout the experiment. No significant changes were found in pulse rate. Both groups gained weight similarly. Exchangeable sodium increased at the same rate in both groups along with the weight increase. Thus, chronic hydralazine treatment effectively reduces blood pressure in spontaneously hypertensive rats without causing measurable sodium or fluid retention.     

Antihypertensive Agents Prevent Nephrosclerosis and Left Ventricular Hypertrophy Induced in Rats by Prolonged Inhibition of Nitric Oxide Synthesis

We investigated the ability of the angiotensin converting enzyme (ACE) inhibitor imidapril hydrochloride, and of the calcium channel blocker amlodipine besilate, to prevent nephrosclerosis and left ventricular hypertrophy (LVH) in rats with hypertension induced by chronic inhibition of nitric oxide (NO). Male Wistar rats were given distilled water (control), N^G-nitro- -arginine methyl ester (L-NAME) 500 mg/L, L-NAME plus imidapril 10 mg/L or 100 mg/L, or L-NAME plus amlodipine 50 mg/L or 100 mg/L in the drinking water (n = 10–12). We then collected 24-h urine samples at 2, 4, and 6 weeks, obtained blood samples at 6 weeks, and histologically examined the kidney and heart. L-NAME markedly reduced the levels of NO metabolites in serum and urine while increasing the tail-cuff blood pressure, the urinary albumin level (1.90 + 0.65 v 0.05 + 0.02 mg/day/100 g in control), and the area of the left ventricular wall (83.3 + 3.0 v 69.8 + 1.8 mm² in control). Nephrosclerosis and myocardial interstitial fibrosis were documented histologically. The plasma renin activity was significantly higher in rats treated with L-NAME than in the control rats. The concomitant administration of imidapril (10 mg/L) with L-NAME completely normalized the tail-cuff pressure, the LVH (70.8 + 1.8 mm²), the albuminuria (0.05 + 0.01 mg/day/100 g), and the histologic changes. Amlodipine (50 mg/L) also ameliorated the L-NAME–induced effects, but to a lesser extent. Thus, the chronic inhibition of NO synthesis in rats produced nephrosclerosis and LVH that were effectively prevented by giving imidapril at a dose lower than that of amlodipine. We conclude that ACE inhibitors can prevent nephrosclerosis and LVH even in the presence of a reduction in NO production, implying that in rats the inhibition of the renin-angiotensin system is more effective than the blockade of calcium channels in preventing hypertensive tissue injury.     

Effect of Chronic Alcohol Ingestion on the Heart and Blood Pressure of Spontaneously Hypertensive Rats

The effect on the heart of a combination of high blood pressure and chronic alcohol ingestion was studied in spontaneously hypertensive rats (SHR) fed ethanol in their drinking water in concentrations of O%, 5% and 20% for sixteen weeks. Normotensive Wistar rats were used as controls (NCR). In addition some SHR were given alcohol for a shorter period of eight weeks at the end of which time there were no significant differences in mean arterial blood pressure between the groups. After sixteen weeks of ethanol the mean arterial pressure had fallen in those SHR receiving 20% ethanol to 136 ± 24 mmHg compared to control (180 ± 27 mmHg; P < 0.001). This was associated with a lower left ventricular (LV) dp/dt (control 4800 ± 872 mmHg sec^?1; 20% ethanol group = 3450 ± 1588 mmHg sec^?1; P < 0.025) and a reduced LV weight (corrected for body weight) due to an apparent lack of development of LV hypertrophy between eight and sixteen weeks. Similarly LV volume (corrected for LV weight), did not change from eight weeks to sixteen weeks in those SHR receiving 20% ethanol in contrast to the 0% ethanol SHR group in whom LV volume fell as LV hypertrophy developed. 5% Ethanol had no significant effect on mean arterial pressure, LV peak dp/dt, LV weight or LV volume. In the NCR ethanol had little effect on mean arterial pressure but those receiving 20% ethanol had significantly smaller LV volumes without any increase in LV weight probably reflecting blood volume depletion. Ethanol did not produce any blood pressure elevation in the NCR. No rats (SHR or NCR) develped overt heart failure or a typical cardimyo-pathy. However, this study has shown that a high intake of ethanol reduces the blood pressure of a hypertensinve rat most likely by its direct toxic action on the myocardium. Thus with chronic alcohol ingestion hypertension can be masked but may still contribute significantly to the development of myocardial disease.     

Effect of Vasopressin Blockade on Blood Pressure in Conscious Rats with Malignant Two-Kidney Goldblatt Hypertension

The role of vasopressin (VP) in maintaining blood pressure in malignant two-kidney one-clip Goldblatt hypertension in chronically catheterized conscious rats was investigated by studying the effect of two structurally different VP pressor antagonists. Injections of either 20 µg/kg of dPTyr(Me)AVP or 10 µg/kg of d(CH₂)₅Tyr(Me)AVP failed to alter mean arterial pressure or heart rate, although both antagonists completely inhibited the pressor response elicited by exogenous VP. These results suggest, that VP is not involved as a pressor hormone in the maintenance of high blood pressure in this type of experimental hypertension.     

Coronary artery thrombosis and thrombolysis in baboons: the effect of atenolol treatment on myocardial infarct size

The effect of the beta-blocker atenolol on experimental infarctsize was studied in a non-human primate model. In 12 baboonsthrombosis of the left anterior descending coronary artery (LAD)was induced and atenolol (0·1 to 0·2 mg . kg^–1intravenously, sufficient to lower the heart rate by 20%) wasadministered 10 mm after the onset of ischaemia in six animals,whereas the others received placebo. Thrombolysis was induced60 mm after the onset of ischaemia by intravenous injectionof rt PA (12 µg. kg^–1. min^–1) in all animals. Heart rate dropped signficantly after atenolol injection (128±9beats . min^–1 versus 163±15 beats . min^–1,P<0001) and was also lower than in the control group (128±9beats. min^–1 versus 158±22 beats.min^–1, p<0·05).Blood pressure remained unchanged after atenolol treatment.As compared to the control group, atenolol limited infarct size,expressed as a percentage of left ventricular mass (4·6±1·9%versus 7·9±1·3%, P<0·05 or asa percentage of the perfusion area (26±8% versus 43%8%,P<0·05).     

罗格列酮对自发性高血压大鼠的降压作用

目的 为了初步了解胰岛素增敏剂罗格列酮对自发性高血压大鼠的降压作用和机理，设计了本项实验。方法 自发性高血压大鼠36只，随机分为3组，罗格列酮和硝苯吡啶分别作为观察药和阳性对照药添加到大鼠饮水中，另有一组空白对照。结果 2种药物均呈现显著的降压作用，但血胰岛素水平测量结果没有达到显著的统计学差异。结论 胰岛素增敏剂—罗格列酮可以显著降低自发性高血压大鼠的血压，其机理有待深入探讨。     

Hypertensive Diabetic Rats: Different Effects of Streptozotocin Treatment on Blood Pressure in Adult SHR and in Neonatal SHR

The effect of streptozotocin (STZ) treatment on blood pressure in adult spontaneously hypertensive rats (SHR) was compared with that in neonatal SHR. Three-month-old SHR were intravenously given 10, 30 or 50 mg/kg of STZ. When STZ was given in adult SHR, weight loss, overt hyperglycemia and the reduction of blood pressure occurred dose dependently. Two-day-old pups from SHR were subcutaneously injected with 100 mg/kg of STZ. Neonatal STZ treatment did not attenuate the development of hypertension in SHR. Since neonatally STZ-treated SHR develop mild diabetic symptom with hypertension and develop mild diabetic glomerulosclerosis, they are a good model for studying vascular complications or other disorder relating to the synergism between hypertension and diabetes mellitus.     

Coronary artery thrombosis and thrombolysis in baboons: the effect of atenolol treatment on myocardial infarct size.

The effect of the beta-blocker atenolol on experimental infarct size was studied in a non-human primate model. In 12 baboons thrombosis of the left anterior descending coronary artery (LAD) was induced and atenolol (0.1 to 0.2 mg.kg-1 intravenously, sufficient to lower the heart rate by 20%) was administered 10 min after the onset of ischaemia in six animals, whereas the others received placebo. Thrombolysis was induced 60 min after the onset of ischaemia by intravenous injection of rtPA (12 micrograms.kg-1.min-1) in all animals. Heart rate dropped significantly after atenolol injection (128 +/- 9 beats.min-1 versus 163 +/- 15 beats.min-1, P less than 0.001) and was also lower than in the control group (128 +/- 9 beats.min-1 versus 158 +/- 22 beats.min-1, P less than 0.05). Blood pressure remained unchanged after atenolol treatment. As compared to the control group, atenolol limited infarct size, expressed as a percentage of left ventricular mass (4.6 +/- 1.9% versus 7.9 +/- 1.3%, P less than 0.05) or as a percentage of the perfusion area (26 +/- 8% versus 43 +/- 8%, P less than 0.05).