噻吗洛尔和氢氯噻嗪对血压、心率及血浆肾素活性的定量影响：原发性高血压患者双盲析因试验结果

Quantitative effects of timolol and hydrochlorothiazide on blood pressure, heart rate and plasma renin activity: results of a double-blind factorial trial in patients with essential hypertension.

Chalmers J P, Horvath J S, Korner P I, Tiller D J, Bune A J, England J D, Fletcher P J

Clin Sci Mol Med Suppl. 1976 Dec;3:517s-519s. doi: 10.1042/cs051517s.

Abstract

The anti-hypertensive actions of timolol and hydrochlorothiazide were analysed in a double-blind 2 x 2 factorial trial in twenty patients with essential hypertension. Each patient went through four phases of 8 weeks in randomized order, receiving timolol alone, hydrochlorothiazide alone, timolol plus hydrochlorothiazide, and placebo. 2. Supine mean arterial pressure fell from 119 mmHg in the placebo phase, to 110 mmHg during the thiazide phase, 106 mmHg during the timolol phase, and to 101 mmHg during the combined timolol plus hydrochlorothiazide phase. 3. Factorial analysis revealed that the hypotensive actions of the beta-receptor-blocking drug and the diuretic were additive, without any synergism or antagonism. 4. Plasma renin activity measured in ng 3 h-1 ml-1 rose from 5-02 in the placebo phase to 9-54 in the diuretic phase, but fell to 1-79 in the beta-receptor blockade. It was unchanged in the combined therapy phase, despite the greater drop in blood pressure. These results suggest that the fall in plasma renin activity during beta-receptor blockade is of little importance in the hypotensive action of beta-receptor-blocking drugs.

摘要

在一项针对20例原发性高血压患者的双盲2×2析因试验中，分析了噻吗洛尔和氢氯噻嗪的降压作用。每位患者按随机顺序经历四个为期8周的阶段，分别单独服用噻吗洛尔、单独服用氢氯噻嗪、噻吗洛尔加氢氯噻嗪以及服用安慰剂。2. 仰卧位平均动脉压从安慰剂阶段的119 mmHg降至噻嗪类药物阶段的110 mmHg、噻吗洛尔阶段的106 mmHg以及噻吗洛尔加氢氯噻嗪联合阶段的101 mmHg。3. 析因分析显示，β受体阻滞剂和利尿剂的降压作用是相加的，没有任何协同或拮抗作用。4. 以ng 3 h⁻¹ ml⁻¹为单位测量的血浆肾素活性从安慰剂阶段的5.02升至利尿剂阶段的9.54，但在β受体阻滞时降至1.79。在联合治疗阶段，尽管血压下降幅度更大，但血浆肾素活性并未改变。这些结果表明，β受体阻滞期间血浆肾素活性的下降在β受体阻滞剂的降压作用中不太重要。