Floras J S, Jones J V, Hassan M O, Sleight P
Br Med J (Clin Res Ed). 1982 Nov 13;285(6352):1387-92. doi: 10.1136/bmj.285.6352.1387.
Intra-arterial ambulatory blood pressure was measured over 24 hours, in 34 patients with newly diagnosed hypertension, both before and after double-blind randomisation to treatment with atenolol (n=9), metoprolol (n=9), pindolol (n=9), or propranolol in its slow-release form (n=7). The dosage of each drug was adjusted at monthly clinic visits until satisfactory control of blood pressure was achieved (140/90 mm Hg or less by cuff) or the maximum dose in the study protocol was reached. A second intra-arterial recording was made after these drugs had been taken once daily at 0800 for three to eight months (mean 5.0+/-SD 1.4) and was started four hours after the last dose.At the end of the 24-hour recordings blood pressure was significantly lower with all four drugs. The extent to which the drugs reduced blood pressure, however, differed over the 24 hours. Atenolol lowered mean arterial pressure significantly throughout all 24 recorded hours, metoprolol for 12 hours, pindolol for 15 hours, and slow-release propranolol for 22 hours. Neither metoprolol nor pindolol lowered blood pressure during sleep. A significant reduction in heart rate was observed over 20 hours with atenolol, 20 hours with metoprolol, 10 hours with pindolol, and 24 hours with slow-release propranolol. Atenolol, metoprolol, and slow-release propranolol continued to slow the heart rate 24 hours after the last tablet was taken; this effect on heart rate, however, was not sustained throughout the second morning in those patients taking atenolol. Pindolol, the only drug studied that has intrinsic sympathomimetic activity, increased heart rate and did not lower blood pressure during sleep.Atenolol and slow-release propranolol are effective as antihypertensive agents over 24 hours when taken once daily, whereas metoprolol and pindolol may need to be taken more frequently. At times of low sympathetic tone, however, such as during sleep, beta-blockers with intrinsic sympathomimetic activity may raise heart rate and attenuate the fall in blood pressure with treatment.
对34例新诊断的高血压患者在双盲随机分组接受阿替洛尔（n = 9）、美托洛尔（n = 9）、吲哚洛尔（n = 9）或缓释普萘洛尔（n = 7）治疗之前和之后，均进行了24小时动态动脉血压测量。每种药物的剂量在每月的门诊就诊时进行调整，直到血压得到满意控制（袖带测量为140/90 mmHg或更低）或达到研究方案中的最大剂量。在这些药物每天08:00服用三至八个月（平均5.0±标准差1.4）且在最后一剂后4小时开始进行第二次动脉内记录。在24小时记录结束时，所有四种药物的血压均显著降低。然而，这些药物在24小时内降低血压的程度有所不同。阿替洛尔在所有24个记录小时内均显著降低平均动脉压，美托洛尔降低12小时，吲哚洛尔降低15小时，缓释普萘洛尔降低22小时。美托洛尔和吲哚洛尔在睡眠期间均未降低血压。阿替洛尔在20小时内、美托洛尔在20小时内、吲哚洛尔在10小时内以及缓释普萘洛尔在24小时内观察到心率显著降低。在服用最后一片药24小时后，阿替洛尔、美托洛尔和缓释普萘洛尔仍继续使心率减慢；然而，在服用阿替洛尔的患者中，这种对心率的影响在第二个早晨并未持续。吲哚洛尔是唯一研究的具有内在拟交感活性的药物，它会增加心率且在睡眠期间不降低血压。阿替洛尔和缓释普萘洛尔每天服用一次时作为抗高血压药物在24小时内有效，而美托洛尔和吲哚洛尔可能需要更频繁地服用。然而，在交感神经张力较低时，如睡眠期间，具有内在拟交感活性的β受体阻滞剂可能会增加心率并减弱治疗时血压的下降。
