van den Meiracker A H, Admiraal P J, Man in 't Veld A J, Derkx F H, Ritsema van Eck H J, Mulder P, van Brummelen P, Schalekamp M A
Department of Internal Medicine I, University Hospital Dijkzigt, Rotterdam, The Netherlands.
BMJ. 1990 Jul 28;301(6745):205-10. doi: 10.1136/bmj.301.6745.205.
To investigate the effects of a novel specific renin inhibitor, RO 42-5892, with high affinity for human renin (Ki = 0.5 x 10(-9) mol/l), on plasma renin activity and angiotensin II concentration and on 24 hour ambulatory blood pressure in essential hypertension.
Exploratory study in which active treatment was preceded by placebo.
Inpatient unit of teaching hospital.
Nine men with uncomplicated essential hypertension who had a normal sodium intake.
Two single intravenous doses of RO 42-5892 (100 and 1,000 micrograms/kg in 10 minutes) given to six patients and one single oral dose (600 mg) given to the three others as well as to three of the patients who also received the two intravenous doses.
With both intravenous and oral doses renin activity fell in 10 minutes to undetectably low values, while angiotensin II concentration fell overall by 80-90% with intravenous dosing and by 30-40% after the oral dose. Angiotensin II concentration was back to baseline four hours after the low and six hours after the high intravenous dose and remained low for at least eight hours after the oral dose. Blood pressure fell rapidly both after low and high intravenous doses and after the oral dose and remained low for hours. With the high intravenous dose the daytime (0900-2230), night time (2300-0600), and next morning (0630-0830) systolic blood pressures were significantly (p less than 0.05) lowered by 12.5 (95% confidence interval 5.6 to 19.7), 12.2 (5.4 to 19.3), and 10.7 (3.2 to 18.5) mm Hg respectively, and daytime diastolic pressure was lowered by 9.3 (2.2 to 16.8) mmHg. With the oral dose daytime, night time, and next morning systolic blood pressures were lowered by 10.3 (5.5 to 15.4), 10.5 (4.2 to 17.2), and 9.7 (4.0 to 15.6) mm Hg, and daytime and night time diastolic pressures were lowered by 5.8 (0.9 to 11.0) and 6.0 (0.3-12) mm Hg respectively.
The effect of the inhibitor on blood pressure was maintained over a longer period than its effect on angiotensin II. RO 42-5892 is orally active and has a prolonged antihypertensive effect in patients who did not have sodium depletion. This prolonged effect seems to be independent, at least in part, of the suppression of circulating angiotensin II.
研究一种对人肾素具有高亲和力（Ki = 0.5×10⁻⁹ mol/l）的新型特异性肾素抑制剂RO 42 - 5892对原发性高血压患者血浆肾素活性、血管紧张素II浓度及24小时动态血压的影响。
探索性研究，在积极治疗前先给予安慰剂。
教学医院的住院部。
9名无并发症的原发性高血压男性患者，钠摄入正常。
6名患者接受两次静脉注射RO 42 - 5892（10分钟内分别为100和1000微克/千克），另外3名患者及其中3名也接受两次静脉注射的患者口服一次剂量（600毫克）。
静脉注射和口服剂量后，肾素活性在10分钟内降至检测不到的低水平，静脉给药后血管紧张素II浓度总体下降80 - 90%，口服给药后下降30 - 40%。低剂量静脉注射后4小时和高剂量静脉注射后6小时，血管紧张素II浓度恢复至基线水平，口服给药后至少8小时保持低水平。静脉注射低剂量和高剂量后以及口服给药后血压迅速下降，并持续数小时保持低水平。高剂量静脉注射后，白天（09:00 - 22:30）、夜间（23:00 - 06:00）和次日早晨（06:30 - 08:30）收缩压分别显著降低（p < 0.05）12.5（95%置信区间5.6至19.7）、12.2（5.4至19.3）和10.7（3.2至18.5）mmHg，白天舒张压降低9.3（2.2至16.8）mmHg。口服给药后，白天、夜间和次日早晨收缩压分别降低10.3（5.5至15.4）、10.5（4.2至17.2）和9.7（4.0至15.6）mmHg，白天和夜间舒张压分别降低5.8（0.9至11.0）和6.0（0.3至12）mmHg。
该抑制剂对血压的影响比其对血管紧张素II的影响持续时间更长。RO 42 - 5892具有口服活性，对无钠缺乏的患者有持久的降压作用。这种持久作用似乎至少部分独立于循环血管紧张素II的抑制作用。
