硝苯地平联合卡托普利治疗原发性高血压的疗效研究

目的研究硝苯地平联合卡托普利治疗原发性高血压的疗效。方法收集本院收治的原发性高血压患者临床资料,在给予硝苯地平联合卡托普利治疗后,监测患者的血压、蛋白尿以及高血压引起的心绞痛缓解情况。结果用药后,2组平均血压值均发生明显下降,治疗组疗效明显好于对照组。对照组心绞痛的缓解情况明显好于治疗组,而治疗组治疗后24 h尿蛋白明显下降,低于对照组。结论硝苯地平和卡托普利对于原发性高血压有较好疗效,总体有效率达到95%,尤其对于伴有蛋白尿的高血压患者能够显著改善蛋白尿的状况。     

Dose response in captopril therapy of hypertension

Dose-response curves of blood pressure and of the biochemical components of the renin-angiotensin-aldosterone system were determined during long-term treatment with captopril in 21 hypertensive patients. Captopril was given in biweekly, doubling doses starting with 25 mg 3 times a day until control of blood pressure was achieved or a total daily dosage of 600 mg was reached. Recumbent and standing systolic and diastolic blood pressure fell on 75 mg captopril daily. Increasing the captopril dose did not induce further significant hypotensive effects. The pretreatment level of plasma renin activity (PRA) was a poor predictor of the hypotensive effect of captopril. The rises in PRA and plasma angiotensin I level (PA I) and the decrease in plasma angiotensin II level (PA II) and plasma aldosterone level (PAC) provide biochemical evidence for angiotensin-converting enzyme (ACE) inhibition in vivo. These effects were present on daily doses of 75 to 150 mg captopril.     

Prehospital use of nifedipine for severe hypertension

The prehospital management of severe hypertension is limited by a paucity of pharmacologic agents suitable for field use. This prospective study was designed to test the safety and efficacy of intraoral nifedipine therapy in 50 patients with severe hypertension being transported by an urban emergency medical service system. Ten milligrams of nifedipine were administered. Serial blood pressure determinations were obtained at 3, 5, 10, and 15 minutes and patients were observed for possible side effects. A marked effect on systolic blood pressure (SP), diastolic blood pressure (DP), and mean arterial pressure (MAP) was evident and was statistically significant in all three categories by 3 minutes. MAP decreased from 169 to 129 mm Hg (delta MAP of 40 mm Hg) at 15 minutes with parallel changes in the SP (55 mm Hg) and delta DP (32 mm Hg). These changes were highly significant (P less than .01) when compared with those of 50 historical controls. No evidence of severe adverse effects were noted. Nifedipine appears to be a promising agent for the prehospital treatment of severe hypertension, but its proper role is not yet defined.     

Therapy comparison between the combination hydergine/nifedipine and nifedipine alone in patients with isolated systolic hypertension

The effect of Hydergine/Nifedipine (Pontuc) on blood pressure in supine or exercise blood pressure as well as subjective well-being was evaluated in a randomized, double-blind interindividual comparison with Nifedipine in 50 elderly out-patients (34 females, 16 males) with mostly pretreated isolated systolic hypertension. In addition to a nearly unchanged diastolic blood pressure during treatment the results prove that the drop in systolic blood pressure was statistically significant greater after treatment with Hydergine/Nifedipine and the normalization rate of the blood pressure was 81% in comparison to 69% after Nifedipine. Both drugs comparatively improved the subjective well-being of these geriatric patients. As drug specific adverse events flush symptoms were more frequent in the Nifedipine group, whereas in the Hydergine/Nifedipine group gastrointestinal symptoms occurred more often.     

Assessment of the efficacy and tolerance of delayed-action nifedipine as the monotherapy or in combination with metoprolol in patients with arterial hypertension

AIM: To compare efficacy and safety of nifedipin-retard (cordaflex-retard, Egis, Hungary) used in monotherapy and in combination with metoprolol (egilok, Egis, Hungary) in patients with arterial hypertension (AH). MATERIAL AND METHODS: The study included 20 patients with AH stage I-II (12 males, 8 females, mean age 57.3 years, mean duration of the disease 8.6 years). Nifedipin-retard was given in a daily dose 40 mg/day (20 mg twice a day) in monotherapy and 20 mg/day in combination with metoprolol which was administered 50 mg twice a day (a daily dose 100 mg/day). The control examination consisted of a physical examination, measurement of arterial pressure (AP) by Korotkov, registration of heart rate, ECG, 24-h AP monitoring, echocardiography. RESULTS: By 24-h AP monitoring, a 4-week treatment with nifedipin-retard alone resulted in lowering of systolic arterial pressure. The combined treatment produced a more pronounced fall both in systolic and diastolic pressure. Diastolic left-ventricular function improved in combined therapy. Side effects observed in nifedipin-retard monotherapy got much more weaker when this drug combined with metoprolol. CONCLUSION: Combination of nifedipin-retard with metoprolol provides better clinical response and tolerance than monotherapy with nifedipin-retard.     

奈比洛尔联用卡托普利对原发性高血压大鼠动脉舒血管效应的影响

目的 观察奈比洛尔对原发性高血压大鼠(SHR)血压以及不同动脉对血管紧张素转换酶抑制剂卡托普利舒血管效应的影响.方法 将16只SHR随机分成奈比洛尔治疗组(奈比洛尔8 mg·kg-1·d-1灌胃,n=8)和SHR组(灌胃等量蒸馏水,n=8).以同周龄的雄性正常血压Wistar-Kyoto(WKY)大鼠作为对照(n=8).给药8周后,无创法测定尾动脉收缩压;处死动物后取胸主动脉、颈动脉、肾动脉、股动脉,观察卡托普利(1×10-8～3×10-4 mol/L)舒血管效应的变化.结果 与SHR组相比,奈比洛尔可明显抑制SHR血压升高[(152±27)mm Hg比(203±36)mm Hg,1 mm Hg=0.133 kPa,P<0.05).SHR组颈动脉对卡托普利的最大舒张效应(Emax)小于WKY对照组,使预收缩张力舒张50%所需浓度(EC50)大于WKY对照组(均P<0.05);主动脉、肾动脉、股动脉的Emax和EC50在SHR组与WKY对照组间比较差异无统计学意义.奈比洛尔可增加SHR组主动脉、颈动脉、肾动脉、股动脉对卡托普利的Emax,并降低主动脉、股动脉EC50(均P<0.05),而对颈动脉和肾动脉EC50则无影响.结论 奈比洛尔可增加SHR血管对卡托普利的舒张效应.     

拜新同与北京降压0号或海捷亚合用治疗老年性单纯性收缩期高血压疗效观察

目的：观察和分析拜新同分别联合北京降压0号或海捷亚治疗老年性单纯性收缩期高血压（ISH）的疗效及对代谢的影响。方法：选择83例老年ISH患者随机分为3组，拜新同组（A组，n=28，拜新同30mg，1次／d），拜新同与北京降压0号合用组（B组，n=28，拜新同30mg，1次／d，北京降压0号1片，1次／d），拜新同与海捷亚合用组（C组，n=27，拜新同30mg，1次／d，海捷亚50mg，1次／d）。3组治疗疗程均为12周，观察3组治疗前后的血压及肝肾功能、血糖、血脂、电解质等指标的变化。结果：B、C组降压总有效率相当，其对随测血压、24h动态血压的控制疗效接近；B、C组血压控制效果明显优于A组；3组治疗前后心率及生化指标无明显改变。结论：拜新同与北京降压0号或海捷亚合用降低老年ISH均有较显著且相似的疗效．与单用拜新同比较效果更好。     

The renin-angiotensin system during converting enzyme inhibition with captopril in patients with severe treatment-resistant hypertension

Abstract. The effect of captopril on blood pressure (BP) and various components of the renin-angiotensin system was assessed in ten severely hypertensive patients. Captopril acutely reduced the BP with a maximum decrease of 23% at 90–120 min.
Maintenance treatment with captopril alone could not control the BP in any of the patients. Addition of hydrochlorothiazide markedly reduced the BP, while supplementation with propranolol caused no consistent changes.
Three patients attained a supine diastolic blood pressure (SDBP) ≤90 mmHg. Only two patients had a fall in SDBP less than 10 mmHg. One patient stopped because of taste disturbances.
Monitoring the renin-angiotensin system showed suppressed plasma concentrations of angiotensin II and increased levels of angiotensin I and renin, indicating the inhibition of converting enzyme activity. Plasma concentration of renin substrate decreased significantly. This observation has important implications for the methodology of renin assays.
Captropril is an effective alternative in the treatment of hypertensive patients not readily controlled with conventional therapy.     

巯甲丙脯酸、酚妥拉明、多巴胺、硝苯地平和山莨菪碱对肾综合征出血热患者肾功能的影响

目的：了解巯甲丙脯酸、酚妥拉明、多巴胺、硝苯地平和山莨菪碱对肾综合征出血热（ＨＦＲＳ）患者肾功能的影响，为临床选择改善肾功能的药物提供依据。方法：选择ＨＦＲＳ患者２１０例，随机分为巯甲丙脯酸组、酚妥拉明组、多巴胺组、硝苯地平组、山莨菪碱组和对照组，每组３５例。对照组仅用综合治疗法，其余各组均在综合治疗的基础上分别加用上述药物。结果：巯甲丙脯酸组、酚妥拉明组、多巴胺组、硝苯地平组、山莨菪碱组在尿蛋白消失时间、尿素氮复常时间、少尿期发生率、少尿期和多尿期持续时间方面均优于对照组，尤以巯甲丙脯酸组和酚妥拉明组最为明显。结论：巯甲丙脯酸、酚妥拉明、硝苯地平、多巴胺和山莨菪碱能促进ＨＦＲＳ患者肾功能的恢复，而以巯甲丙脯酸和酚妥拉明为优。提示ＨＦＲＳ患者可常规应用巯甲丙脯酸、酚妥拉明、硝苯地平、多巴胺和山莨菪碱；对于重症患者，可联合应用２种～３种上述药物。     

Combined use of nifedipine and diltiazem for the treatment of severe hypertension

Calcium channel blockers are a heterogeneous group of drugs that have enhanced our ability to concurrently control blood pressure, treat coronary artery disease, and avoid many of the side effects of previously available antihypertensive agents. Patients with severe hypertension may require multiple agents for adequate control of blood pressure because of either poor control with one agent or side effects from high doses of a single agent. Laboratory investigations have shown a synergistic effect on receptor binding, as well as increased drug levels with the concurrent use of diltiazem and a dihydropyridine calcium channel blocker (nifedipine or nicardipine). It is as yet unknown whether these effects on receptor binding and increased drug levels translate into greater clinical efficacy in blood pressure control. We have reported what we believe to be the first case in which this interaction was used successfully to control previously poorly controlled hypertension, while minimizing side effects.     

高原地区以卡托普利缓释片为基础的联合降压治疗对高危高血压住院患者血压控制的影响

目的 探讨高海拔地区高危高血压住院患者以卡托普利缓释片为基础的联合降压治疗效果.方法 331例住院高血压患者依据血压值、危险因素和合并靶器官损害分为高危组(229例)和低危组(102例),高危组给予以卡托普利缓释片为基础的联合降血压治疗,低危组给予单一降压治疗,比较2组出院血压水平以及住院期间的降压幅度和出院血压达标率.结果 高危组患者收缩压、舒张压降压幅度均显著大于低危组[收缩压降幅分别为(36.83 ±22.23)、(28.74±18.71)mm Hg,舒张压降幅分别为(22.04±13.57)、(17.98±13.63)mm Hg,t值分别为-3.207、-2.509,P均<0.05),出院时平均收缩压[(125.62±14.74)、(122.28±13.13)mm Hg,t=-1.962]、舒张压[(80.67±9.82)、(78.40±9.97)mm Hg,t=-1.910]均达标且2组间比较差异无统计学意义(P均>0.05).住院期间血压治疗控制率高危组为72.06%(165/229),低危组为71.57%(73/102),2组间比较差异无统计学意义(x2=0.928,P>O.05).结论 在高海拔地区以卡托普利缓释片为基础的联合降压治疗是适合高危高血压患者降压治疗方案,能取得较满意的血压治疗控制率.

Abstract：

Objective To investigate the blood pressure control effect of captopril sustained-releasetablets based combination, antihypertensive therapy on hospitalized high-risk patients with hypertension in high altitude region. Methods According to the blood pressure,risk factors and combined target organ damage,331 hospitalized patients with essential hypertension were divided into 2 groups and accepted different treatment:low-risk group had monotherapy (n=102) , and night-risk group had captopril sustained-release-tablets based combination antihypertensive therapy (n =229). The discharge blood pressure,extent of SBP/DBP decrease and the compliance rate of discharge blood pressure of two groups were compared. Results The extent of SBP/DBP decrease in hight-risk group was significantly greater than low-risk group (SBP [36. 83 ± 22. 23] mm Hg vs.[28. 74 ±18.71] mm Hg,t=-3. 207,P <0. 05;DBP[22. 04±13. 57]mm Hg vs. [17. 98 ± 13.63] mm Hg,t =-2. 509, P < 0.05). The average discharge blood pressure in both groups reach the standard criterion, but no significant difference was observed between the two groups (SBP [125. 62 ± 14. 74] mm Hg vs. [122. 28 ±13.13]mmHg,t=-1. 962,P>0. 05;DBP[80. 67 ±9. 82]mm Hg vs. [78. 40 ±9. 97]mm Hg,t =-1.910,P > 0. 05). Furthermore we found no significant difference in the control rate of blood pressure between high-risk and low-risk group (72. 06% vs. 71. 57% , x2 = 0.928, P > 0. 05). Conclusion The captopril sustainedrelease-tablets based combination antihypertensive therapy is a reliable treatment in high-risk patients with hypertension from high altitude region,which shows satisfying blood pressure control rate.     

Treatment of arterial hypertension with ketanserin in mono- and combination therapy

We evaluated the long-term antihypertensive effects of ketanserin, a selective serotonin2-receptor blocker with weak adrenergic receptor blocker properties. Ketanserin was given alone, 40 mg o.d. or b.i.d., for 2 years to 12 patients with essential hypertension. Systolic and diastolic blood pressures (BPs) were significantly reduced 14 days after the start of therapy and remained lowered during the 2-year follow-up period. In a larger group of patients who received ketanserin monotherapy for 2 to 3 months, the response to therapy varied considerably between subjects, with an overall response rate (BP less than 165/95 mm Hg) of 60% to 75%. During steady-state conditions, the maximum and minimum ketanserin plasma concentrations varied from threefold to fourfold between subjects and did not correlate with individual reductions in BP, but for each individual there was a positive correlation between BP reduction and ketanserin plasma concentration throughout a study day. In combination with beta-blockers, ketanserin effectively reduced BP in the supine and standing positions. The plasma concentration profile was not altered as much during combination therapy as when ketanserin was given alone. Side effects were few and tolerable. Ketanserin effectively reduces BP both alone and in combination with beta-blockers and may be still another drug useful in the treatment of essential hypertension.     

Managing hypertension using combination therapy

Combination therapy of hypertension with separate agents or a fixed-dose combination pill offers the potential to lower blood pressure more quickly, obtain target blood pressure, and decrease adverse effects. Antihypertensive agents from different classes may offset adverse reactions from each other, such as a diuretic decreasing edema occurring secondary to treatment with a calcium channel blocker. Most patients with hypertension require more than a single antihypertensive agent, particularly if they have comorbid conditions. Although the Joint National Committee guidelines recommend diuretic therapy as the initial pharmacologic agent for most patients with hypertension, the presence of "compelling indications" may prompt treatment with antihypertensive agents that demonstrate a particular benefit in primary or secondary prevention. Specific recommendations include treatment with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics, beta blockers, or aldosterone antagonists for hypertensive patients with heart failure. For hypertensive patients with diabetes, recommended treatment includes diuretics, beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and/or calcium channel blockers. Recommended treatment for hypertensive patients with increased risk of coronary disease includes a diuretic, beta blockers, angiotensin-converting enzyme inhibitors, and/or calcium channel blocker. The Joint National Committee guidelines recommend beta blockers, angiotensin-converting enzyme inhibitors, and aldosterone antagonists for hypertensive patients who are postmyocardial infarction; angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for hypertensive patients with chronic kidney disease; and diuretic and angiotensin-converting enzyme inhibitors for recurrent stroke prevention in patients with hypertension.     

Capozide-50 alone and in combination with melatonin in therapy of hypertension

Monotherapy with caposide-50 (C-50) was compared to combined therapy C-50 + melatonin in 22 patients with essential hypertension stage II (mean age 60 years). The patients were divided into two groups. Group 1 received C-50 at 8.00 a.m., group 2 received C-50 at 8.00 a.m. and melatonin at 10.00 p.m. in a dose 3 mg. Before the treatment and 14 days after it echo-CG was made to assess hemodynamics. Also, 24-h monitoring of arterial pressure was performed. The findings were analysed with variance statistics and cosinor-analysis. Group 1 achieved a moderate hypotensive effect. Circadian rhythm of systolic blood pressure was abnormal. Group 2 patients achieved more pronounced decline of systolic, diastolic and mean arterial pressures. Circadian rhythm of these pressure did not return to normal.     

Bisoprolol alone and in combination with amlodipine or nifedipine in the treatment of chronic stable angina

Beta-blockers and calcium antagonists are both effective monotherapy for stable angina. When symptoms persist, these two agents are commonly co-prescribed in the hope that this combination has added benefit compared with monotherapy alone. We investigated the additional efficacy of the calcium antagonists amlodipine and nifedipine when added to bisoprolol in patients with stable angina. Patients were randomised in a multicentre, single-blind study, with crossover of three treatments consisting of bisoprolol 10 mg once daily, bisoprolol plus nifedipine 20 mg twice daily, and bisoprolol plus amlodipine 5 mg once daily. Exercise tests were performed at the end of each four-week study period and the exercise time to onset of angina was assessed. A total of 198 patients from 17 centres were recruited of whom 147 were evaluable for efficacy. There were no statistically significant differences in exercise duration to onset of angina between any of the groups. The combination of bisoprolol plus nifedipine was least well tolerated. In summary, this study suggests there is little benefit in adding a calcium antagonist to bisoprolol in treating patients with stable angina.     

Reduction of plasma and urinary vasopressin during treatment of severe hypertension by captopril

Abstract. Plasma concentrations and urinary excretion rate of vasopressin (VP) were examined in ten cases of severe hypertension before and during short-term treatment by Captopril (SQ 14 225). Before Captopril, plasma and urinary VP were high (respectively 5.24 pmol/1 and 68 pmol/day) and positively correlated to plasma renin activity (PRA) and plasma aldosterone (PA). The decline in blood pressure (mean —15%) after Captopril was correlated not only to initial PRA and PA values, but also to plasma ( r = 0.89; P < 0.001) and urinary ( r = 0.78; P < 0.01) VP values. The initial dose of Captopril (1 mg/kg) induced a rapid decrease in blood pressure whereas plasma VP did not rise and aldosterone decreased. At the eighth day of Captopril treatment (mean daily dose 6±1.5 mg/kg) the drop in blood pressure (— 12%) and in aldosterone persisted together with a significant reduction in plasma (1.18 pmol/1; P <0.01) and urinary (25 pmol/day; P <0.01) VP. It is suggested that these sustained simultaneous reductions in the rates of secretion of vasopressin and aldosterone are both elements of the antihypertensive effect of Captopril.     

Comparative effect of captopril and nifedipine in normotensive patients with incipient diabetic nephropathy

In these studies, the effect of a 6-wk treatment by placebo, the calcium-channel blocker nifedipine, or the converting-enzyme inhibitor captopril was assessed in normotensive patients with insulin-dependent diabetes and incipient nephropathy. In response to captopril and nifedipine, arterial pressure decreased slightly and to a similar extent. These drugs resulted in opposite effects on urinary excretion of albumin [i.e., increase in urinary albumin excretion (UAE) by 40% during nifedipine treatment and decrease by 40% during captopril treatment]. No change in UAE was observed in the placebo group. This observation of opposite changes in UAE in the presence of a similar fall in arterial pressure suggests that the effects of captopril and nifedipine on UAE result from some difference in their intrarenal action. The data do not present recommendations for the use or disuse of captopril or nifedipine in such a group of patients and do not allow extrapolation to hypertensive diabetic subjects well controlled by other conventional antihypertensive agents.