Amery A, Billiet L, Boel A, Fagard R, Reybrouck T, Willems J
Am Heart J. 1976 May;91(5):634-42. doi: 10.1016/s0002-8703(76)80149-4.
The mechanism of the hypotensive effect during beta-adrenergic blockade in hypertension was studied in 38 patients with renal or essential hypertension using the new cardioselective beta blocker, Tenormin. During 5 weeks hospitalization the patients received first a placebo for 5 to 12 days, then a 75 mg. dose of Tenormin was given daily for 1 week, and thereafter the dose was doubled weekly as necessary up to 600 mg. daily. The blood pressure decreased from 180 +/- 26.2/118. "/- 13.6 mm. Hg on placebo to 151 +/-25.5/96 +/-13.8 mm. Hg during the final hospitalization period on Tenormin (600 mg. daily). Six patients developed fluid retention and as this occurred blood pressure control was lost. A subsequent follow-up on an outpatient basis of 15 of the patients showed that when the active drug was replaced by a placebo blood pressure rose again, confirming that the initial fall in blood pressure was a genuine effect. Multistage bicycle ergometer exercise tests were performed at weekly intervals to test the degree of beta blockade and indicated that this was nearly complete when a dose of 600 mg. per day was used. A significant correlation between the hypotensive effect and the degree of beta blockade, assessed by exercise tachycardia, was observed. A slight but statistically significant decrease (26 per cent) was observed in the plasma renin concentration, measured recumbent in the morning. This decrease was, however, not correlated with the hypotensive effect of the drug. Although the cardiac output decreased significantly (from 5.5 +/-1.7 to 4.3 +/- 1.1 L per minute, p less than 0.001), no correlation was found in individual patients between the cardiac output and the blood pressure decrease. On the other hand, for the total group of catheterized patients (n = 28) the calculated total peripheral resistance did not change significantly. Yet a significant correlation was found between the changes in total resistance and the hypotensive effect. This suggests that the reaction of the peripheral vessels rather than the cardiac output decrease determines whether the drug will produce a major decrease of blood pressure in patients with hypertension.
采用新型心脏选择性β受体阻滞剂氨酰心安，对38例肾性或原发性高血压患者进行了β肾上腺素能阻滞剂降压作用机制的研究。在为期5周的住院期间，患者首先服用5至12天的安慰剂，然后每天给予75毫克氨酰心安，持续1周，此后根据需要每周将剂量加倍，直至每天600毫克。血压从服用安慰剂时的180±26.2/118±13.6毫米汞柱降至住院末期服用氨酰心安（每天600毫克）时的151±25.5/96±13.8毫米汞柱。6例患者出现液体潴留，出现这种情况时血压控制丧失。随后对15例患者进行门诊随访，结果显示当活性药物被安慰剂替代时血压再次升高，证实最初的血压下降是真实效应。每周进行一次多级自行车测力计运动试验，以检测β受体阻滞程度，结果表明，每天使用600毫克剂量时，β受体阻滞几乎完全。观察到通过运动性心动过速评估的降压作用与β受体阻滞程度之间存在显著相关性。早晨卧位测量的血浆肾素浓度略有下降，但具有统计学意义（26%）。然而，这种下降与药物的降压作用无关。虽然心输出量显著下降（从每分钟5.5±1.7升降至4.3±1.1升；p＜0.001），但在个体患者中未发现心输出量与血压下降之间存在相关性。另一方面，对于全部行导管插入术的患者（n = 28），计算得出的总外周阻力没有显著变化。然而，在总阻力变化与降压作用之间发现了显著相关性。这表明外周血管的反应而非心输出量的下降决定了该药物是否会使高血压患者的血压大幅下降。
