拉西地平对高血压大鼠的降压作用

目的：观察新的钙拮抗剂拉西地平的降压作用。方法：急性降压实验：将５个月龄雄性卒中型自发性高血压大鼠（ＳＨＲｓｐ）随机分为Ａ、Ｂ、Ｃ（分别经管饲给药１次，拉西地平剂量１ｍｇ／ｋｇ，０．５ｍｇ／ｋｇ，０．２５ｍｇ／ｋｇ）、Ｄ（尼群地平１０ｍｇ／ｋｇ）、Ｅ（溶媒对照）组，每组１１只，于用药后１、３、５、９、１２、２４小时各测１次收缩压及心率（尾套法）。慢性降压实验：将３个月龄ＳＨＲｓｐ分为Ａ、Ｂ、Ｄ、Ｅ组（剂量同急性降压实验），每组１０只，治疗１４天，于治疗后第２、４、６、８、１０、１２、１４天各测１次收缩压及心率。结果：拉西地平１ｍｇ／ｋｇ和０．５ｍｇ／ｋｇ均可显著降低ＳＨＲｓｐ血压，降压作用分别持续１２～２４小时和９～１２小时，降压作用均强于尼群地平１０ｍｇ／ｋｇ，仅轻度增加了心率。结论：拉西地平对ＳＨＲｓｐ降压作用明确，持续时间长。     

氨氯地平与苯那普利对高血压脑梗塞患者脑血流动力学的影响

目的研究氨氯地平和苯那普利对高血压脑梗塞患者脑血流动力学的影响。方法４５例高血压脑梗塞患者随机与为氨氯地平组２５例（５ｍｇ，１／ｄ），苯那普利组２０例（５ｍｇ，１／ｄ），疗程４周。治疗前后１３３Ｘｅ吸入法测定脑血流量及经颅三维多普勒检查，２０例健康人作为正常对照组。结果氨氯地平组及苯那普利组降血压总有效率分别为８８．０％和８５．０％（χ２＝０．０２，Ｐ＞０．０５），治疗后两组脑血流量及脑血流速度均比治疗前增加（Ｐ＜０．０５～０．０１），氨氯地平组比苯那普利组稍明显，但两组差异无统计学意义。结论氨氯地平和苯那普利均能良好控制高血压脑梗塞患者血压。     

中国老年收缩期高血压临床试验总结报告

目的研究降压治疗能否降低老年收缩期高血压患者的脑卒中和其它心血管并发症的发生和死亡率。方法采用随机、安慰剂对照的研究方法。入选病例总数为２３９４例。１２５３例患者分入尼群地平组，尼群地平的用量为１０～４０ｍｇ／ｄ，必要时加用卡托普利１２．５～５０ｍｇ／ｄ和（或）双氢克尿噻１２．５～５０ｍｇ／ｄ。１１４１例患者分入对照组，给予相应的安慰剂治疗。结果入选时坐位血压的平均值为１７０．５／８６．０ｍｍＨｇ（１ｍｍＨｇ＝０．１３３ｋＰａ），平均年龄６６．５岁，总胆固醇５．１ｍｍｏｌ／ｌ，经过４年的随访，治疗组和对照组血压均明显下降，两组间坐位收缩压和舒张压差异分别为８．０ｍｍＨｇ和３．２ｍｍＨｇ。经过降压治疗脑卒中降低了３８％（Ｐ＝０．０１），全病因死亡率降低了３９％（Ｐ＝０．００３），心血管病死亡率降低了３９％（Ｐ＝０．０３），致死性脑卒中降低了５８％（Ｐ＝０．０２），所有的致死和非致死性心血管事件降低了３７％（Ｐ＝０．００４）。结论每治疗１０００例老年收缩期高血压患者５年可减少５５例死亡，３９例脑卒中或５９例主要的心血管事件的发生。     

尼群地平伍用倍他乐克对高血压病的治疗及随访

目的：探讨尼群地平伍用倍他乐克治疗高血压病的医疗效果。方法：１３４例高血压病患分为两组：观察组与对照组。观察组８６例,服用尼群地平,１０～２０ｍｇ／次,２～３次／日,伍用倍他乐克１２．５～５０ｍｇ／次,２次／日;对照组４８例,用开搏通片,１２．５～２５ｍｇ／次,２～３次／日,疗程４周。测血压,１次／日。根据血压、心率变化调整用药方案,直到血压正常或接近正常。之后,每月监测血压１～２次,坚持长期随     

静脉地尔硫治疗快速房颤、房扑的疗效分析

为检验静脉地尔硫艹卓控制房颤、房扑心室率的有效性和安全性，对４７例快速房颤、房扑患者一次静脉注射０．２５ｍｇ／ｋｇ地尔硫艹卓后以５ｍｇ／ｈ～１０ｍｇ／ｈ微泵维持，平均起效时间５．２±２．７ｍｉｎ，总有效率９３．６％，心功能较用药前明显改善（Ｐ＜０．０５），对血压无明显影响，副作用发生率为１０．６％，均不严重。结果提示地尔硫艹卓是一种能迅速、安全、有效控制房颤、房扑患者心室率的药物     

高血压家族遗传因素与心血管病危险因素聚集关系的研究

目的：探讨高血压遗传因素与心血管病危险因素聚集的关系。方法：采用家系调查方法，对比分析高血压家系和对照家系直系亲属的危险因素个体聚集性。共调查高血压家系２５个，含直系亲属１５８例，其中包括高血压患者５４例，血压正常者１０４例；对照家系１５个，含直系亲属６５人。结果：超重（体重指数＞２５ｋｇ／ｍ２），高甘油三酯（甘油三酯＞２．０ｍｍｏｌ／Ｌ），高尿酸血症（男：尿酸＞３７４．９ｍｍｏｌ／Ｌ；女：尿酸＞３１５．４ｍｍｏｌ／Ｌ），高胰岛素血症（胰岛素＞１２．２μｍｏｌ）及低高密度脂蛋白胆固醇（低高密度脂蛋白胆固醇＜０．９１ｍｍｏｌ／Ｌ）５个危险因素中，具有１个以上至５个以上上述危险者的年龄标化百分比在高血压家系明显高于对照家系，将高血压家系中高血压患者剔除后比较，这种规律依然存在。结论：高血压家族遗传因素可能对心血管病危险因素聚集起着重要的作用     

舌下含服硝酸甘油加口服降压药对高血压急诊降压时程的影响

４５例急诊高血压患者，舌下含服硝酸甘油２ｍｉｎ后，血压开始下降，１５ｍｉｎ后下降幅度最大（５０±１０／２８±７ｍｍＨｇ）。０．５，１ｈ后各组血压均较治疗前明显下降（Ｐ＜０．００１），２，５．１０ｈ后，没有口服降压药组（对照组），血压逐渐升高，与口服降压药组（用药组）比较差异显著（Ｐ＜０．０５）．５，１０ｈ后，对照组血压明显升高与其用药前比较无显著差异（Ｐ＞０．０５）．用药组血压仍无明显升高，与其用药前比较差异显著（Ｐ＜０．０５）。研究表明，两药合用对降低急诊高血压的降压时程有显著相加作用。     

不同术前药的冠心病病人术中冠脉搭桥术入液量对血流动力学的 …

将８０例冠脉搭桥病人随机双盲分为：Ａ组（对照组,ｎ＝４０）;Ｂ组（试验组,ｎ＝４０）。Ａ组术前１ｈ口服安定１０ｍｇ、术前３０ｍｉｎ肌注吗啡０．１５～０．２ｍｇ／ｋｇ和东莨菪碱０．３ｍｇ。Ｂ组术前药增加口服氨酰心安６．２５～１２．５ｍｇ及硫氮唑酮３０ｍｇ。分别观察体外循环（ＣＰＢ）前２组病人在不同入液量下的各项血流动力学指标。Ａ组与Ｂ组病人诱导后静脉入液量分别为６５２．５ｍｌ及６５７．５;开胸前分别     

亚剂量吡喹酮对慢性血吸虫病患者循环抗原水平的影响

目的观察不同亚治疗剂量吡喹酮对慢性血吸虫病患者血清血吸虫肠相关趋阴极抗原（ＧＡＣＡ）水平的影响。方法ＫａｔｏＫａｔｚ法粪检确定１０８例慢性血吸虫病患者，随机分成４组，分别给予口服５ｍｇ／ｋｇ、１０ｍｇ／ｋｇ、２０ｍｇ／ｋｇ剂量吡喹酮和安慰剂。采用单克隆抗体酶联免疫吸附试验（ＭｃＡｂＤｏｔＥＬＩＳＡ）分别检测服药前、后２、８、２４和４８小时患者血清ＧＡＣＡ水平。服药前、后检出率变化采用χ２检验。结果３个实验组服药后２小时检测血清ＧＡＣＡ水平，平均较服药前上升３个滴度，后渐下降；至服药后４８小时，血清ＧＡＣＡ水平仍高于服药前１个滴度。血清ＧＡＣＡ检测敏感性，可由服药前的８２．７％提高到服药后２小时的１００．０％（Ｐ＜０．０５）。对照组４８小时观察期内，血清ＧＡＣＡ水平波动在１个滴度范围内，检测敏感性无明显变化（Ｐ＞０．０５）。结论口服不同亚治疗剂量吡喹酮均能有效升高慢性血吸虫病患者血清血吸虫ＧＡＣＡ水平，并显著提高血清ＧＡＣＡ检测敏感性。     

RU486对正常人和库欣综合征患者垂体—肾上腺轴的影响及…

本文观察了１０例正常人和１４例库欣综合征患者垂体－肾上腺轴在单次口服ＲＵ４８６ ４ｍｇ／ｋｇ后的反应。正常人在８ｐｍ口服ＲＵ４８６后连续２天８Ａｍ的血促肾上腺皮质激素（ＡＣＴＨ）和皮质醇（Ｆ）均明显升高（Ｐ〈０．０１，Ｐ〈０．００１），服药后第一天２４ｈ尿Ｆ亦明显升高（Ｐ〈０．００１）。库欣综合征组服药后连续观察２天上述激素水平无明显改变。正常组服药后连续２天的血Ｆ，ＡＣＴＨ及２４ｈ尿Ｆ较服药前所     

Ketanserin and hydrochlorothiazide in the treatment of arterial hypertension

The chronic antihypertensive effect of the combination of ketanserin (KET) 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg was evaluated in 20 patients with arterial hypertension of mild to moderate degree. After a 2-week wash-out period, patients were prescribed a single oral dose of KET 40 mg or HCTZ 25 mg in a randomized order at 2-day intervals and blood pressure and heart rate were measured during the following 24 hrs by an automatic recorder. Thereafter patients were given the combination of KET 40 mg + HCTZ 12.5 mg for 6 weeks and 24 hrs blood pressure was recorded after the first dose of the combination and at the end of treatment. Ketanserin induced a significant fall in systolic and diastolic pressures for up to 8 hrs; thiazide did not induce any change in these parameters. The combination of KET + HCTZ in the acute study reduced significantly systolic (SBP) and diastolic (DBP) blood pressures for up to 10 hrs. After 6 weeks of treatment with KET + HCTZ, blood pressure showed a further fall at each time period and was normalized (BP greater than 160/80 mmHg) for 8 hrs after dosing. The results of this study indicate that once daily oral administration of the combination of KET 40 mg + HCTZ 12.5 mg in mild to moderate primary hypertensives significantly reduces blood pressure over 24 hrs. Fairly good control of BP, i.e. BP less than 160/90 mmHg, was, however, achieved only up to 8 hrs after drug administration, indicating that this combination given once daily is not able to normalize BP over the following 24 hrs.     

Impact of body mass index on platelet aggregation after administration of a high loading dose of 600 mg of clopidogrel before percutaneous coronary intervention

This study assessed the effect of body mass index (BMI) on platelet aggregation after administration of a high loading dose of clopidogrel 600 mg. Blood samples of 402 patients before percutaneous coronary intervention were collected >or=2 hours after administration of clopidogrel 600 mg. Platelet aggregation was measured in response to adenosine diphosphate (ADP; 5 and 20 microM). Patients were categorized as normal weight (BMI <25 kg/m(2)) or overweight (BMI >or=25 kg/m(2)). ADP-induced platelet aggregation was significantly higher in overweight patients than in normal-weight patients (46.0 +/- 21.8% vs 38.2 +/- 19.3% for ADP 5 microM, p = 0.0007; 55.1 +/- 22.7% vs 45.2 +/- 21.7% for ADP 20 microM, p <0.0001). Multivariate analyses demonstrated high BMI as the only independent predictor for increased ADP-induced platelet aggregation (p 相似文献   

Synergism of atenolol and nitrendipine on hemodynamic amelioration and organ protection in hypertensive rats

OBJECTIVE: This study was designed to investigate the possible synergism of atenolol and nitrendipine on blood pressure (BP) and blood pressure variability (BPV) reductions, baroreflex sensitivity (BRS) amelioration, and organ protection in hypertensive rats. METHOD: The dose was 20 mg/kg for atenolol, 10 mg/kg for nitrendipine and 20 + 10 mg/kg for the combination of these two drugs. In an acute study, a single dose was given via a catheter previously inserted into the stomach in spontaneously hypertensive rats (SHR). In a subacute study, SHR, deoxycorticosterone acetate (DOCA)-salt rats, and two-kidney, one-clip (2K1C) rats were used. They received the same dose by gavage daily for 10 days. BP was measured 24 h after drug administration. In chronic studies, these drugs at the aforementioned dose were mixed into rat chow. SHR were treated for 4 months. BP was then continuously recorded for 24 h. After the determination of BRS, rats were killed for organ-damage evaluation. RESULTS: In the acute study, it was found that the combination of atenolol and nitrendipine had an obviously greater and longer BP reduction than treatment with each of these two drugs separately. In the subacute study, an effective decrease in BP 24 h after administration was found only in the rats treated with the combination. In chronic studies, it was found that the combination possessed the obvious synergism on BP and BPV reduction, BRS amelioration and organ protection in SHR. Multiple-regression analysis showed that the decrease in left ventricular hypertrophy was most significantly related to the decrease in systolic BPV and BP, the decrease in aortic hypertrophy was most significantly related to the increase in BRS and the decrease in systolic BPV, and amelioration in the renal lesion was most significantly associated with the restoration of BRS. CONCLUSION: Treatment with a combination of atenolol and nitrendipine exhibited a rapid and persistent antihypertensive effect and possessed an obvious synergism on BP and BPV reduction, BRS restoration and organ protection in hypertensive rats. The decrease in BPV and the restoration of BRS may importantly contribute to organ protection in SHR with chronic treatment.     

Aliskiren, a novel, orally effective renin inhibitor, lowers blood pressure in marmosets and spontaneously hypertensive rats

OBJECTIVES: Aliskiren is a new renin inhibitor of a novel structural class that has recently been shown to be efficacious in hypertensive patients after once-daily oral dosing. We report the results of animal experiments performed in marmosets and rats in order to characterize aliskiren before its recent investigation in humans. METHODS: The effects of aliskiren were investigated in sodium-depleted marmosets (oral dosing) and in spontaneously hypertensive rats (dosing via subcutaneous osmotic minipumps). Blood pressure (BP) and heart rate were measured by radiotelemetry. RESULTS: In sodium-depleted marmosets, single oral doses of aliskiren (1-30 mg/kg) dose-dependently lowered BP. At a dose of 3 mg/kg, peak effects were observed 1 h after dosing (-30 +/- 4 mmHg, n = 6) and the response persisted for more than 12 h. A single oral dose of 3 mg/kg aliskiren was more effective than the same dose of either remikiren or zankiren, two orally active renin inhibitors previously tested in humans. Aliskiren (10 mg/kg) was at least as effective as equal doses of the AT1-receptor blocker valsartan or the angiotensin-converting enzyme inhibitor benazepril. In spontaneously hypertensive rats, aliskiren dose-dependently (10-100 mg/kg per day) decreased BP. Aliskiren also potentiated the antihypertensive effects of low doses of valsartan or benazeprilat (1 or 3 mg/kg per day). CONCLUSIONS: Aliskiren is an orally effective, long-lasting renin inhibitor that shows antihypertensive efficacy in animals superior to previous renin inhibitors and at least equivalent to angiotensin-converting enzyme inhibitors and AT1-receptor blockers. Aliskiren may therefore represent an effective, novel approach to the treatment of hypertension and related disorders, alone or in combination with other antihypertensive agents.     

Systolic Hypertension in Europe (Syst-Eur) trial phase 2: objectives, protocol, and initial progress. Systolic Hypertension in Europe Investigators

The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (> or = 60 years) patients with isolated systolic hypertension (systolic BP > or = 160 mm Hg and diastolic BP < 95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial. This open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. To lower the sitting systolic BP below 150 mm Hg (target BP), the first-line agent nitrendipine (10-40 mg/day) may be associated with enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. On 1 November 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. The median follow-up in Syst-Eur 2 was 14.3 months. At the last available visit, systolic/diastolic BP in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Ci: 0.8 to 2.6 mm Hg; P < 0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P < 0.001). At the beginning of Syst-Eur 2, the goal BP was reached by 25.4% and 50.6% of the former placebo and active-treatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. At that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. Until the end of 2001, BP control of the Syst-Eur 2 patients will be further improved. Cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, will be monitored and validated by blinded experts.     

Effectiveness of reloading to overcome clopidogrel nonresponsiveness in patients with acute myocardial infarction

Whether increasing doses of clopidogrel can overcome nonresponsiveness was evaluated. Clopidogrel nonresponsiveness was found in up to 25% of treated patients and was associated with worse prognosis in patients with acute coronary syndrome and patients undergoing coronary intervention. Adenosine diphosphate (ADP)-induced platelet aggregation was prospectively determined on day 4 of acute myocardial infarction in 200 consecutive patients, who received clopidogrel 300 mg as a loading dose and 75 mg/day thereafter. Thirty patients (15%) had ADP-induced platelet aggregation >or=80% using light transmittance aggregometry and were considered clopidogrel nonresponders. Nonresponders were reloaded with clopidogrel 600 mg, followed by 150 mg/day for 4 weeks. A 75-mg/day dose was resumed thereafter. ADP-induced platelet aggregation was reassessed 4 hours after reloading and biweekly for 10 weeks. Flow cytometry was used to determine platelet P-selectin expression and fibrinogen binding before and 4 hours after reloading. ADP-induced platelet aggregation significantly decreased 4 hours after reloading (from 83 +/- 6% to 56 +/- 14%; p <0.01). The decrease in platelet aggregation was maintained throughout the 4-week doubled maintenance dose. After resuming a maintenance dose of 75 mg/day, ADP-induced platelet aggregation returned to 66 +/- 12% (p <0.001), and 5 patients (17%) had ADP-induced platelet aggregation >or=80%. Flow cytometry showed a significant decrease in P-selectin expression (from 37 +/- 16% to 26 +/- 13%; p <0.01) and fibrinogen binding (from 84 +/- 7% to 70 +/- 13%; p <0.01) in ADP-stimulated platelets 4 hours after reloading. In conclusion, clopidogrel reloading and increased maintenance dose may overcome clopidogrel nonresponsiveness in patients with acute myocardial infarction.     

Amiloride compared with nitrendipine in treatment of essential hypertension

The antihypertensive effect of amiloride was compared to that of the calcium antagonist nitrendipine in 12 patients (8 males), aged 34-62 years, with essential hypertension WHO grade I-II (mean supine blood pressure 158/103, standing 155/106 mmHg) in a double-blind placebo-controlled cross-over study design. Amiloride was given 5 mg once daily for one month followed by 20 mg twice daily for another month. Amiloride 5 mg once daily significantly reduced supine and standing DBP but not SBP (supine 151/94, standing 149/97 mmHg), whereas 10 mg once daily decreased SBP as well as DBP (supine 145/98, standing 145/101 mmHg). Nitrendipine 20 mg once daily significantly reduced supine and standing SBP and standing DBP (supine 150/97, standing 148/98 mmHg), but on 20 mg twice daily only supine SBP was significantly reduced (supine 150/99, standing 151/106 mmHg). Heart rate was transiently increased by nitrendipine 20 mg once daily and unchanged following amiloride. Plasma noradrenaline was unaltered following amiloride 10 mg once daily as well as nitrendipine 20 mg twice daily, whereas plasma renin activity and aldosterone were elevated following amiloride. Serum electrolytes, blood glucose, plasma lipids and body weight were not altered by any of the drugs. Amiloride 5-10 mg daily has a mild to moderate BP lowering effect in patients with essential hypertension. The BP reduction following nitrendipine 20 mg once daily was comparable to that of amiloride 5 mg daily. Nitrendipine 20 mg twice daily gave no additional BP decrease.     

Glycoprotein IIb/IIIa antagonist eptifibatide in acute coronary syndrome without elevation of ST segment

Clinical effects of glycoprotein (GP) IIb-IIIa antagonist eptifibatide (Integrilin) and its inhibitory effects on platelet aggregation were studied upon administration of eptifibatide for the treatment of acute coronary syndrome (ACS) without ST segment elevation. Eptifibatide was introduced to 25 patients with unstable angina and non-Q-wave myocardial infarction (MI) according to the following scheme: two boluses with 10 min interval at the dose of 180 mg/kg followed by supporting infusion of 2 mg/kg per min for the first 24 hours and of 1.3 mg/kg for the next 48 hours. Comparative group in which GP IIb-IIIa antagonists were not used upon therapeutic treatment also included 25 patients. All patients received standard basic therapy. 11 patients from the control group and 13 patients from the group with administration of eptifibatide underwent coronary angioplasty during in hospital period. Eptifibatide completely inhibited ADP-induced platelet aggregation within the whole infusion period but after that platelet aggregating activity was quickly recovered--for more than 50% within 6 hours, and completely within 12 hours after the end of infusion. Eptifibatide administration in none of patients was accompanied with the development of dangerous side effects. Thrombocytopenia (50,000 platelets per mm3) was registered in one, and minor bleeding events--in 3 patients. The rate of unfavourable outcomes (MI, refractory or recurrent angina) within first 30 days was almost the same in eptifibatide and control group--32% (8 out of 25) and 36% (9 out of 25) respectively. Thus, despite the complete inhibition of platelet aggregation for 72 hours, eptifibatide administration failed to decrease the amount of adverse events upon treatment of patients with ACS without ST segment elevation.     

A double-blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days.

AIMS: We sought to test whether an increase in the clopidogrel maintenance dose results in increased inhibition of platelet aggregation. METHODS AND RESULTS: Sixty patients after pre-treatment with 600 mg of clopidogrel and within 12 h after successful PCI were included in this trial. They were allocated to receive one of two clopidogrel daily maintenance doses (75 or 150 mg) for 30 days in a double-blind randomized manner. Platelet function was evaluated 30 days after the intervention with optical aggregometry and with a new point-of-care test (VerifyNowtrade mark P2Y12 assay). Maximal 5 microM ADP-induced platelet aggregation 30 days after PCI in the group treated with 150 mg/day clopidogrel (45.1 +/- 20.9%) was significantly lower than in the group treated with 75 mg/day (65.3 +/- 12.1%; P < 0.001). The VerifyNowtrade mark P2Y12 assay also indicated a higher degree of platelet function inhibition in the group treated with 150 mg/day (60.0 +/- 72.0 P2Y12 Reaction Units) than in the group treated with 75 mg/day (117.0 +/- 64.3 P2Y12 Reaction Units; P = 0.004). CONCLUSION: Administration of a 150 mg oral maintenance dose of clopidogrel results in more intense inhibition of platelet aggregation than administration of the currently recommended 75 mg maintenance dose.     

Hemodynamic and endocrine responses to guanfacine in normotensive volunteers and hypertensive patients

The centrally acting alphamimetic antihypertensive drug, guanfacine, was studied in normotensive volunteers and patients with essential and renal hypertension. After acute (0.02 mg/kg, intravenously) and short-term (mean dose: 6.7 mg/day orally for 4 weeks) administration of guanfacine, systolic, diastolic and mean blood pressures (BPs), heart rate, cardiac output and right atrial pressure were measured by standard techniques. Cardiac index, stroke volume and total peripheral vascular resistance were calculated. After medium-term therapy (mean dose: 6 mg/day orally for 12 weeks), antihypertensive efficacy, as well as plasma renin activity and catecholamine levels, was determined. After intravenous administration, guanfacine lowered systolic, diastolic and mean arterial BPs after a brief and transient increase. Guanfacine exerted its antihypertensive action primarily by its effect on total peripheral resistance. Reflex tachycardia was not observed. Heart rate was reduced. Stroke volume increased and right atrial pressure decreased. These effects were maintained or enhanced during the 4 weeks of oral therapy that followed. In the 12-week study, significant reductions in systolic, diastolic and mean BPs were observed. With a constant dose of 3 mg/day for 1 week, BP decreased from 197/115/149 (systolic/diastolic/mean) to 166/97/126 mm Hg. After 4 weeks at varying doses, BP decreased to 157/91/118, and after 12 weeks, to 147/83/109. In the 12 patients treated for 4 weeks with 3 mg/day, a significant decrease from 192/111/145 to 151/87/114 mm Hg was observed, while in the 6 patients treated for 12 weeks with the 3 mg/day dose, the final readings showed a decrease of 50 mm Hg in systolic pressure, 30 mm Hg in diastolic pressure and 38.4 mm Hg in mean arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)