原发性高血压患者中肾素抑制剂Ro 42 - 5892与血管紧张素转换酶抑制剂依那普利对血压及血管紧张素反应的比较。

Comparison of blood pressure and angiotensin responses to the renin inhibitor Ro 42-5892 and the angiotensin converting enzyme inhibitor enalapril in essential hypertension.

作者信息

van den Meiracker A H, Admiraal P J, Derkx F H, Kleinbloesem C, Man in 't Veld A J, van Brummelen P, Mulder P, Schalekamp M A

机构信息

Department of Internal Medicine I, University Hospital Dijkzigt, Rotterdam, The Netherlands.

出版信息

J Hypertens. 1993 Aug;11(8):831-8. doi: 10.1097/00004872-199308000-00010.

DOI:10.1097/00004872-199308000-00010

PMID:8228207

Abstract

OBJECTIVE

To compare the responses of angiotensin II (Ang II) and blood pressure to the renin inhibitor Ro 42-5892 and the angiotensin converting enzyme (ACE) inhibitor enalapril.

SUBJECTS

Eight non-sodium-restricted patients with mild-to-moderate essential hypertension.

DESIGN

A single-blind crossover study. Ro 42-5892 (600 mg orally, once a day) and enalapril (20 mg orally, once a day) were given for 8 days before detailed investigations were carried out.

METHODS

Ambulatory blood pressure was measured directly for 24 h by the Oxford technique on three occasions. Off-treatment and on day 8 of treatment with Ro 42-5892 and with enalapril. Ang II was measured by radioimmunoassay after separation by high-performance liquid chromatography.

RESULTS

Plasma renin activity and Ang II were lowered by 83% [95% confidence interval (CI) 61-105] and 68% (95% CI 49-87), respectively, 0.5-1 h after Ro 42-5892, but after only 3 h values had returned to baseline. Unlike this rapid and short-term suppression of Ang II, the maximal antihypertensive response to Ro 42-5892 (fall in blood pressure 12.9/9.0 mmHg) occurred only after 6 h. Blood pressure returned to baseline after 8 h. In response to enalapril, Ang II was maximally suppressed by 63% (95% CI 32-94) after 2 h and by 83% (95% CI 76-90) after 8 h. Despite early maximal Ang II suppression, the maximal antihypertensive response to enalapril occurred only after 12 h (fall in blood pressure 25.3/16.3 mmHg). With this compound a significant antihypertensive effect was still present 24 h after dosing.

CONCLUSIONS

Compared with enalapril at 20 mg once a day, repeated oral administration of a single dose of Ro 42-5892 at 600 mg caused only short-term suppression of Ang II and blood pressure. Suppression of Ang II and reduction in blood pressure were temporally dissociated, both with the ACE inhibitor and the renin inhibitor. This implies that the blood pressure lowering effect of these inhibitors is caused partly by Ang II suppression outside the circulation.

摘要

目的

比较血管紧张素II（Ang II）和血压对肾素抑制剂Ro 42-5892及血管紧张素转换酶（ACE）抑制剂依那普利的反应。

受试者

8例非限钠的轻至中度原发性高血压患者。

设计

单盲交叉研究。在进行详细研究前，给予Ro 42-5892（口服600 mg，每日1次）和依那普利（口服20 mg，每日1次），疗程8天。

方法

采用牛津技术，在三个不同时间点直接测量24小时动态血压。分别在停用治疗药物时、使用Ro 42-5892及依那普利治疗的第8天进行测量。通过高效液相色谱分离后，采用放射免疫分析法测定Ang II。

结果

Ro 42-5892给药后0.5 - 1小时，血浆肾素活性和Ang II分别降低83% [95%置信区间（CI）61 - 105]和68%（95% CI 49 - 87），但仅3小时后数值就恢复至基线水平。与这种对Ang II的快速短期抑制不同，Ro 42-5892的最大降压反应（血压下降12.9/9.0 mmHg）仅在6小时后出现。8小时后血压恢复至基线水平。对于依那普利，2小时后Ang II最大抑制率为63%（95% CI 32 - 94），8小时后为83%（95% CI 76 - 90）。尽管早期Ang II被最大程度抑制，但依那普利的最大降压反应仅在12小时后出现（血压下降25.3/16.3 mmHg）。使用该药物给药24小时后仍有显著的降压效果。