缬沙坦与硝苯地平控释片对高血压伴左心室肥厚逆转作用的比较

目的：评价缬沙坦与硝苯地平控释片对高血压伴左心室肥厚的逆转作用并加以比较,以便临床更好用药。方法：将60例原发性高血压伴左心室肥厚患者随机分为缬沙坦组（80mg,qd）及硝苯地平控释片组（30mg,qd）。每组30例。两组均于服药前和服药后6个月时检测血压及超声心动图。结果：两组治疗后血压较治疗前均显著降低（P〈0．01）,组间比较差异无统计学意义;治疗后超声心动图指标LVPWT、IVST、LVDd及LVMI较治疗前均明显下降（P〈0．05）,而LVMI下降尤以缬沙坦组效果更佳（P〈0．05）。结论：缬沙坦与硝苯地平控释片均具有降压和逆转左心室肥厚的作用,但缬沙坦对左心室肥厚的逆转作用相对更强,更利于临床应用。     

多沙唑嗪对映体对麻醉猫心血管功能的选择性作用

目的研究多沙唑嗪对映体对麻醉猫心血管功能的影响。方法采用八道生理仪记录麻醉猫股动脉血压、心率以及左心室收缩压、左心室舒张末期压和左心室内压最大变化率(±dp/dtmax)。结果十二指肠给予右旋多沙唑嗪[(+)doxazosin,(+)DOX]0.03～1.0 mg.kg-1剂量依赖性降低麻醉猫收缩压、舒张压、平均动脉压和左心室收缩压(P<0.05)。十二指肠给予同等剂量的左旋多沙唑嗪[(-)doxazosin,(-)DOX]和消旋多沙唑嗪[(±)doxazosin,(±)DOX]对麻醉猫收缩压、舒张压、平均动脉压和左心室收缩压无影响(P>0.05)。3种药物对左心室舒张末期压、左心室-dp/dt、左心室+dp/dt和心率无影响(P>0.05)。结论麻醉猫十二指肠给药时,(+)DOX降低动脉血压并抑制心室收缩功能,相同剂量的(-)DOX无作用;提示DOX的手性结构对药物的心血管效应具有明显的影响。     

Chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats

AIM: To study chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats. METHODS: In anesthetized rats, the carotid blood pressure, left ventricular pressure of the heart and the urinary bladder pressure were recorded. RESULTS: Administration of S-doxazosin at 0.25, 2.5, 25, and 250 nmol/kg iv produced a dose-dependent decrease in blood pressure, but its depressor effect was significantly weaker than that induced by R-doxazosin and racemic-doxazosin (rac-doxazosin), and the ED(30) values (producing a 30% decrease in mean arterial pressure) of R-doxazosin, rac-doxazosin and S-doxazosin were 15.64, 45.93, and 128.81, respectively. Rac-doxazosin and its enantiomers administered cumulatively in anesthetized rats induced a dose-dependent decrease in the left ventricular systolic pressure and +/-dp/dt(max), and the potency order of the 3 agents was R-doxazosin > rac-doxazosin > S-doxazosin. Rac-doxazosin and its enantiomers decreased the vesical micturition pressure dose-dependently at 2.5, 25, and 250 nmol/kg, and the inhibitory potency among the 3 agents was not significantly different. CONCLUSION: S-doxazosin decreases the carotid blood pressure and left ventricular pressure of the heart less than R-doxazosin and rac-doxazosin, but its effect on the vesical micturition pressure is similar to R-doxazosin and rac-doxazosin, indicating that S-doxazosin has chiral selectivity between cardiovascular system and urinary system in anesthetized rats.     

高血压脑出血的显微外科治疗体会

目的：研究高血压脑出血手术的微创化和减少周围神经组织的继发性损伤。方法：利用小骨窗开颅和显微外科技术治疗２０例高血压脑出血，比较术后患者的生存质量和预后。结果：２０例患者的重残率，死亡率明显下降，术后２４ｈＧＣＳ计分较常规手术组明显提高。讨论：采用显微外科技术可以有效的保护血肿周围组织和重要的豆纹动态穿通支，减少因手术引起的继发性血管损害和血肿周围脑组织梗死。     

Clinical pharmacokinetics of doxazosin in a controlled-release gastrointestinal therapeutic system (GITS) formulation

AIMS: A controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin mesylate, a long-acting selective alpha1-adrenoceptor antagonist, was developed to enhance the pharmacokinetic profile and simplify the titration schedule by precisely controlling drug delivery rate, permitting an initial dose of 4 mg once daily, compared with standard doxazosin, which is initiated at 1 mg day-1 and titrated to a higher therapeutically effective dose. The aim of the present work was to evaluate the pharmacokinetics and bioavailability of doxazosin GITS with respect to the effect of food, age and gender, and multiple dosing. In addition, in vitro performance was assessed in conditions simulating the gastrointestinal environment. METHODS: A three-way crossover study in 24 subjects assessed the comparative bioavailability of doxazosin GITS under fed and fasting conditions and doxazosin standard under fasting condition. A multiple-dose, two-way crossover study in 35 subjects assessed the comparative pharmacokinetics and bioavailability of doxazosin GITS and doxazosin standard 4 and 8 mg upon multiple dosing. A multiple-dose, four-parallel-group study was conducted to determine the steady-state pharmacokinetics and bioavailability of doxazosin GITS 4 mg in 41 young and elderly male and female subjects. The release-rate profiles of doxazosin GITS were determined in artificial gastric fluid (pH=1.2), intestinal fluid (pH=7.5), and water. The effect of agitation on the dissolution characteristics of doxazosin GITS in artificial gastric fluid was studied at stirring rates of 50, 75, and 100 rev min-1. RESULTS: In vitro studies demonstrated that release rates for the GITS tablet are independent of pH in the range of 1.2 (gastric) to 7. 5 (intestinal), and of stirring rates simulating gastrointestinal motility. Clinical pharmacology studies showed that doxazosin GITS had a lower maximum plasma concentration, prolonged time to reach maximum plasma concentration, and a higher minimum plasma concentration compared with doxazosin standard. Thus, the GITS formulation results in a more gradual absorption of doxazosin, and a reduced plasma doxazosin concentration peak-to-trough fluctuation ratio. The relative bioavailability of doxazosin GITS is approximately 60%. With a high-fat meal, the maximum plasma concentration and area under the concentration-time curve were 31% and 18% higher, respectively (P<0.05). Bioequivalence was established between the dose strengths of two 4 mg doxazosin GITS tablets and one 8 mg doxazosin GITS tablet. For both young adult and elderly subjects, and males and females, the pharmacokinetics of doxazosin GITS once daily for 7 days were comparable. Doxazosin GITS was well tolerated in the subjects studied, including young and elderly males and females. CONCLUSIONS: The GITS formulation of doxazosin enhances the pharmacokinetic profile compared with doxazosin standard, allowing more gradual absorption of doxazosin, and a reduced plasma doxazosin peak-to-trough concentration ratio. Thus, doxazosin GITS therapy can be initiated at a therapeutic dose of 4 mg with reduced haemodynamic side-effects.     

多沙唑嗪对映体对大鼠血压和排尿功能的影响

目的观察十二指肠给予多沙唑嗪(rac-DOX)及其对映体(S-DOX、R-DOX)对麻醉大鼠血压和膀胱排尿功能的影响。方法采用八道生理仪记录麻醉大鼠颈总动脉血压、心率以及膀胱排尿压、排尿间隔,并测量排尿量。结果十二指肠给予S-DOX、R-DOX和rac-DOX均可剂量依赖性降低颈总动脉收缩压、舒张压和平均动脉压,1.0mg.kg-1时3者对平均动脉压的降低幅度分别达到23.5%±4.6%、38.5%±8.9%和42.6%±7.5%,3者降低平均动脉压的ED30值依次为(2.0±0.8)、(0.6±0.7)、(0.6±0.5)mg.kg-1。S-DOX降低收缩压、舒张压和平均动脉压的作用均弱于rac-DOX和R-DOX(P<0.05),rac-DOX与R-DOX的降压作用差异无显著性(P>0.05)。rac-DOX在0.1～3.0mg.kg-1剂量范围内剂量依赖性抑制麻醉大鼠心率,而S-DOX和R-DOX仅在3.0mg.kg-1剂量时对心率有抑制作用。十二指肠给予S-DOX、R-DOX和rac-DOX均剂量依赖性降低麻醉大鼠膀胱排尿压,3种药物对排尿压的最大降低幅度分别为13.4%±5.7%、14.5%±11.0%和10.9%±7.6%,3者降低排尿压的作用差异无显著性(P>0.05)。与S-DOX相比,R-DOX可缩短排尿间隔并减少排尿量(P<0.05),而S-DOX和rac-DOX对排尿间隔和排尿量无影响。结论与R-DOX和rac-DOX相比,S-DOX保留了对麻醉大鼠膀胱排尿压的有利作用,减轻了对血压、心率和膀胱排尿间隔的不良影响。     

Effects of preweaning doxazosin treatment on adult pressure in the spontaneously hypertensive rat

1. The neonatal/preweaning period appears to represent a critical period of involvement of the sympathetic nervous system in the development of hypertension in spontaneously hypertensive rats (SHR). 2. We tested whether alpha1-adrenoceptor-mediated effects during the preweaning period are involved in the development of hypertension in the adult SHR. 3. Male SHR were treated with the alpha1-adrenoceptor antagonist doxazosin (10 mg/kg per day, s.c.) from postnatal day 1 to 21 inclusive. Direct conscious blood pressure and heart rate were measured via the caudal artery at 12 weeks of age. 4. Preweaning treatment with doxazosin had no significant effect on mean arterial blood pressure or heart rate in male SHR at 12 weeks of age. 5. These findings do not support the involvement of alpha1-adrenoceptor-mediated effects during the preweaning period in the development of hypertension in adult SHR.     

硝苯地平控释片与普通片治疗老年高血压病比较

目的 比较硝苯地平控释片与普通片对老年高血压患者的降压疗效。方法 采用随机、单盲的方法，对８４例老年高血压患者进行２４ｈ动态血压监测，比较其疗效及副反应。结果 两药均能显著降低老年高血压患者的偶测血压及２４ｈ平均血压（Ｐ〈０．０１）。两药在降低偶测压缩压、２４ｈ平均收缩压及白天平均血压幅度方面差异无显著性（Ｐ〉０．０５），硝苯地平控释片能明显降低患者的偶测舒张压（Ｐ〈０．０５）、２４ｈ平均舒张压（     

Alpha-1 adrenoceptor blockade with doxazosin in hypertension: effects on blood pressure and lipoproteins

The effects of doxazosin, a long-acting alpha-1 adrenoreceptor blocking drug, were observed upon blood pressure and serum lipoproteins. Thirty patients with supine diastolic blood pressure between 90 and 114 mm Hg during single-blind placebo therapy were randomized to double-blind treatment with either doxazosin or further placebo in a parallel-design protocol. Starting at one mg, dosage was doubled every 2 weeks during a 10-week treatment period to a maximum dose of 16 mg once daily. Blood was sampled in the fasting state before and during double-blind therapy for measurement of total cholesterol and triglycerides, cholesterol in the lipoprotein fractions, and apolipoproteins A and B. At the end of 10 weeks of titration, systolic and diastolic blood pressure were each reduced by 14 mm Hg in the standing position when measured 24 hours following the previous dose. Supine pressure was lowered by 6 mm Hg systolic and by 5 mm Hg diastolic at the same time point. Measured hourly for 12 hours following the ingestion of doxazosin, blood pressure was lowered maximally at 4-5 hours when an additional decline of 14/6 mm Hg (systolic/diastolic) was observed in the standing position and 13/6 in the supine posture. Postural dizziness, the most frequent symptomatic complaint, was reported in 4 patients during doxazosin treatment. After brief interruption of treatment in one and dosage adjustment in another, titration was continued in all four and no patient was withdrawn because of side effects. Concerning lipoproteins, the ratio of total cholesterol to HDL cholesterol and of LDL to HDL cholesterol both improved during treatment with doxazosin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of doxazosin on blood pressure and renal haemodynamics of hypertensive patients with renal failure

Doxazosin, a quinazoline derivative, has alpha 1- adrenoreceptor antagonist properties similar to those of prazosin. This antihypertensive agent has a longer elimination half-life than prazosin. The pharmacokinetic properties of doxazosin are not significantly different in patients with renal insufficiency compared with healthy controls. In this study eight hypertensive patients with renal insufficiency were studied during a two week washout period, followed by a two week single blind placebo phase and an eight week open doxazosin treatment period. Doxazosin was commenced in a dose of 1 mg daily and titrated if necessary, with the dose being doubled every two weeks. In all but one patient doxazosin was successful in controlling the blood pressure. Treatment with doxazosin for eight weeks had no adverse effects on the effective renal plasma flow or glomerular filtration rate of these patients. Six of the eight patients suffered side effects attributable to doxazosin.     

代谢综合征的高血压患者收缩压变异性及血压晨峰的研究

目的 探讨代谢综合征的高血压患者收缩压变异性、血压晨峰的临床特征,并分析其与代谢综合征的心血管危险因素之间的相关性。方法 收集门诊高血压患者68例,分成合并有代谢综合征组(A组,n=33)和单纯高血压组(B组,n=35),对两组患者进行24 h动态血压监测(ABPM),连续记录24 h、白天及夜间每半个小时收缩压数值,通过SPSS软件计算24 h、白天及夜间每半小时收缩压均值的标准差,即为24 h收缩压变异性(24 h SBPV),白天收缩压变异性(白天SBPV),夜间收缩压变异性(夜间SBPV);计算起床后2 h内收缩压平均值与夜间睡眠时的收缩压最低值(包括最低值在内的1 h的平均值)的差值即为血压晨峰值。结果 通过对A、B两组收缩压变异性、血压晨峰值进行对比分析,了解合并代谢综合征的高血压患者收缩压变异性、血压晨峰值与单纯高血压患者的区别。同时将代谢综合征定义中包括的多个心血管危险因素与24 h SBPV,白天SBPV,夜间SBPV及血压晨峰值进行相关性分析,探讨与收缩压变异性、血压晨峰相关的影响因素。结论 合并有代谢综合征的高血压患者血压变异性增加。     

Combination of lisinopril and nifedipine GITS increases blood pressure control compared with single drugs in essential hypertensive patients

The present study was designed to evaluate the effect of combination therapy using the angiotensin-converting enzyme-inhibitor lisinopril and the dihydropyridine calcium antagonist nifedipine GITS on the degree and homogeneity of 24-hour blood pressure reduction in essential hypertensive patients. After a 4-week placebo run-in period, 51 patients (mean age, 54.4 +/- 9.4 years) with essential hypertension and clinic diastolic blood pressure between 105 and 115 mm Hg were randomized to 4-week treatment with lisinopril (20 mg), nifedipine GITS (30 mg), or their combination according to a multicenter, randomized, double-blind, crossover study. Trough clinic blood pressure and 24-hour ambulatory blood pressure were measured at the end of the run-in period and after 4 weeks of treatment. In addition to clinic and 24-hour average blood pressure reduction, the trough-to-peak ratio and the smoothness index, a new measure for the homogeneity of blood pressure reduction, were also calculated. Although both lisinopril and nifedipine GITS produced a significant reduction in clinic and 24-hour average blood pressure values, the reduction obtained with the combination was significantly (P < 0.001) greater. Moreover, the combination therapy increased (P < 0.01) the smoothness index as compared with each single drug for both systolic (lisinopril, 1.02; nifedipine GITS, 1.1; combination, 1.76) and diastolic (lisinopril, 0.98; nifedipine GITS, 0.87; combination, 1.54) blood pressure values, whereas trough-to-peak ratio values (expressed as median) for systolic (lisinopril, 0.41; nifedipine GITS, 0.52; combination, 0.55) and diastolic (lisinopril, 0.35; nifedipine GITS, 0.40; combination, 0.49) blood pressure values were not significantly increased by the combination therapy. Thus, antihypertensive treatment with the combination of lisinopril and nifedipine GITS is more effective and balanced over the 24 hours than the combination components administered alone, confirming that the smoothness index is superior to the trough-to-peak ratio in assessing homogeneity of pharmacologic blood pressure reduction.     

拜新同与依苏治疗原发性高血压的疗效比较

目的:观察拜新同与依苏治疗原发性高血压的临床疗效。方法:54例原性高血压患者随机分为依苏组(27例),口服依苏每次10~20mg,每日1次;拜新同组(27例),口服拜新同30~60mg,每日1次,共服用4周。结果:两组治疗一个疗程后收缩压(SBP)、舒张压(DBP)均明显下降(P<0.05),两组血压下降幅度差异无显著性(P>0.05)。结论:拜新同与低苏均可控制原发性高血压,不良反应少。     

Effects of doxazosin in the gastrointestinal therapeutic system formulation versus doxazosin standard and placebo in mild-to-moderate hypertension. Doxazosin Investigators' Study Group

The alpha 1-blocker doxazosin is a well-established therapy for hypertension and benign prostatic hyperplasia; however, in its standard form, a multiple-step titration regimen is usually required. The new gastrointestinal therapeutic system (GITS) formulation of doxazosin greatly minimizes the need for titration by changing drug-delivery rate and the pharmaco-kinetic profile. To demonstrate this in hypertensive patients, we assessed the effects of doxazosin GITS 4 or 8 mg once daily versus doxazosin standard 1-8 mg once daily, and placebo, in an integrated analysis of two multicenter, double-blind, randomized, parallel-group trials. Each trial included a 2-week washout period and 12 weeks of therapy. One study compared doxazosin GITS, doxazosin standard, and placebo in 392 patients with mild hypertension [blood pressure (BP) 95-105/ < or = 180 mm Hg]; the other study compared doxazosin GITS with doxazosin standard in 315 patients with mild-to-moderate hypertension (BP 95-115/ < or = 220 mm Hg). The primary outcome measure was the proportion of responders (sitting diastolic BP < 90 mm Hg or 10-mm Hg decrease from baseline 24 h after the dose) at the final visit for the per-protocol population. Mean baseline BP and heart rate were well matched in each group. Approximately 64% of patients with doxazosin GITS (198 of 309 patients) and 68% with doxazosin standard (207 of 304 patients) achieved goal BP response at the final visit versus 36% with placebo (25 of 70 patients; p < 0.05). The majority with doxazosin GITS (60%) remained at the initial 4-mg starting dose. Doxazosin GITS was as effective as doxazosin standard, and both were more effective than placebo in controlling BP in mild-to-moderate hypertension. Doxazosin GITS was well tolerated, and fewer patients with the GITS formulation discontinued therapy because of side effects compared with doxazosin standard or placebo. Syncope was not reported with doxazosin GITS. Whereas the efficacy of doxazosin GITS at 4 or 8 mg is equivalent to that of the standard regimen in this combined analysis, the GITS formulation appears to eliminate the need for titration in most patients.     

Cadmium-induced nephropathy in the development of high blood pressure

In recognition of a central role of the kidney in long-term blood pressure control, we undertook an in-depth analysis of the relationship between blood pressure and kidney damage caused by environmental exposure to the common pollutants cadmium and lead. The subjects were 200 healthy Thais, 16 and 60 years of age (100 female non-smokers, 53 male non-smokers, and 47 male smokers). None of these subjects had been exposed to Cd or Pb in the workplace and their urinary Cd concentrations ranged from 0.4 to 37 nM, whereas their urinary Pb concentrations ranged from 0.1 to 30 nM. The prevalence of high blood pressure was 2%, 8% and 19%, respectively in subjects with low, average and high Cd-burden (linear trend chi2=6.4, P=0.01). Multiple regression analysis revealed a significant positive association between Cd-burden and blood pressure in male non-smokers (adjusted beta=0.31, P=0.02) and an inverse association between blood pressure and urinary Pb excretion rate in male smokers (adjusted beta=-0.38, P=0.005). Associations between Cd-burden and nephropathies were evidenced by increases in urinary excretion of beta2-microglobulin (P=0.02) and N-acetyl-beta-d-glucosaminidase (P=0.005) in subjects with high Cd-burden, compared with the subjects with average Cd-burden. In addition, an association between Cd-related nephropathy and high blood pressure was evidenced by a 20% increase in the prevalence of high blood pressure in people with NAG-uria (linear trend chi2=4.3, P=0.04). Our present study provides first evidence for a possible link between renal tubular damage and dysfunction caused by environmental Cd exposure and increased risk of high blood pressure.     

Vaccination against high blood pressure

Despite the attractiveness of a vaccination strategy for the treatment of high blood pressure, and many decades of research, attempts to translate this strategy to hypertension management have been unsuccessful. Immunization against components of the renin angiotensin system offers the prospect of improved long-term control of hypertension because efficacy does not require daily compliance with oral medication. Moreover, such a strategy may provide therapeutic benefits beyond blood pressure control, such as improved prevention and treatment of heart failure, and cardiovascular, cerebrovascular, and renal disease. However, despite these potential advantages, there are a number of concerns about the safety and efficacy of this approach. Renin immunization demonstrated effective blood pressure reduction in animal models of hypertension but was accompanied by autoimmune disease of the kidney. Moreover, there are theoretical arguments that angiotensin immunization may have limited effectiveness and clinical studies confirmed these limitations. Vaccination against the angiotensin II type 1 receptor is another possible approach but has yet to undergo clinical evaluation. Thus, the role of vaccination against renin angiotensin system components in hypertension management remains to be established.     

甲基多巴和拉贝洛尔治疗妊娠高血压综合征的临床效果观察

目的 探讨甲基多巴和拉贝洛尔治疗妊娠高血压综合征的临床效果.方法 选取2011年1月～2013年10月于本院门诊就诊的妊娠高血压综合征患者240例,采用随机数字表法将入选患者分为对照组和观察组各120例,观察组采用甲基多巴片口服,250mg/次,3次/d;对照组给予口服盐酸拉贝洛尔片,100 mg/次,2次/d.2个月内检测各组患者的血压及血浆黏度变化情况.结果 与对照组比较,观察组对血压的控制效果更好,治疗后血压更稳定,两组间比较,差异有统计学意义（P＜0.05）;观察组患者的血浆黏度明显低于对照组,差异有统计学意义（P＜0.05）.结论 甲基多巴在预防和治疗妊娠高血压综合征方面有积极的作用,能有效提高治愈率,降低患者血浆黏度,值得临床推广应用.     

Effects of doxazosin and irbesartan on blood pressure and metabolic control in patients with type 2 diabetes and hypertension

The objective of this trial was to compare the metabolic effects of long-term treatment with doxazosin to those of irbesartan in patients with type 2 diabetes and hypertension. We evaluated 96 hypertensive diabetic patients who were randomized to 12 months of double-blind treatment with doxazosin 4 mg/d or irbesartan 300 mg/d. At the end of the study, systolic and diastolic blood pressure (SBP and DBP) were significantly reduced from 152 to 140 mm Hg and from 97 to 87 mm Hg, respectively, with doxazosin (P < 0.01). SBP and DBP were reduced from 150 to 134 mm Hg and from 94 to 83 mm Hg, respectively, with irbesartan (P < 0.01). Irbesartan had significantly better antihypertensive efficacy than doxazosin (P < 0.05). Doxazosin had the greatest effect on glucose metabolism and lipid parameters, with significant (P 相似文献