van den Meiracker A H, Man in 't Veld A J, van Eck H J, Boomsma F, Schalekamp M A
Department of Internal Medicine 1, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands.
Circulation. 1988 Oct;78(4):957-68. doi: 10.1161/01.cir.78.4.957.
Comparison of the hemodynamic and hormonal effects of beta-adrenoceptor antagonists with different ancillary properties may help to clarify the antihypertensive mechanism of these drugs. Under strict basal conditions, the effects of acebutolol (400 mg b.i.d.), atenolol (100 mg b.i.d.), pindolol (10 mg b.i.d.), and propranolol (80 mg t.i.d.), were studied for the first 24 hours in 40 hypertensive patients. With pindolol, mean arterial pressure was reduced (p less than 0.05) 1 hour after administration, whereas the cardiac index and the systemic vascular resistance index did not change. With the other three drugs, the fall in mean arterial pressure was delayed 2-3 hours. With these drugs, the fall in mean arterial pressure was preceded by a rise in the resistance index, which compensated for the initial fall in cardiac index. With each drug, the decrements in mean arterial pressure were associated with parallel decrements in the resistance index, and percent changes in mean arterial pressure and the resistance index were always significantly (p less than 0.001) correlated. At the end of the 24-hour period, the four drugs shared an equal antihypertensive effect, which varied 14-17%. This was associated with a return of the cardiac index toward control values by acebutolol, atenolol, and propranolol treatment and a moderately increased cardiac index above pretreatment values (13%, p less than 0.01) with pindolol. The secondary rise in the cardiac index was inversely correlated (p less than 0.001) with the fall in mean arterial pressure with all four drugs. Plasma renin was maximally suppressed 2 hours after treatment, thus before any change in mean arterial pressure had occurred with acebutolol, atenolol, and propranolol. Pretreatment values of active renin and the reduction of mean arterial pressure 24 hours after administration were not correlated in any of the four groups. Despite the "vasodilator" action of the four drugs, plasma norepinephrine did not rise. Our data show that the main hemodynamic change that occurs at the time blood pressure falls after beta-adrenoceptor antagonism is vasodilation. Neither autoregulation of blood flow nor renin suppression can explain this vasodilator action. The absence of an increase in norepinephrine, despite vasodilation, suggests that beta-adrenoceptor antagonism interferes with sympathetic vasoconstrictor nerve activity. This effect may explain the vasodilator and antihypertensive potential of beta-adrenoceptor antagonists.
比较具有不同辅助特性的β-肾上腺素能受体拮抗剂的血流动力学和激素效应，可能有助于阐明这些药物的降压机制。在严格的基础条件下，对40例高血压患者在最初24小时内研究了醋丁洛尔（400毫克，每日两次）、阿替洛尔（100毫克，每日两次）、吲哚洛尔（10毫克，每日两次）和普萘洛尔（80毫克，每日三次）的效应。使用吲哚洛尔后，给药1小时后平均动脉压降低（p<0.05），而心脏指数和全身血管阻力指数未改变。使用其他三种药物时，平均动脉压的下降延迟2 - 3小时。使用这些药物时，平均动脉压下降之前阻力指数升高，这补偿了心脏指数的初始下降。使用每种药物时，平均动脉压的降低与阻力指数的平行降低相关，平均动脉压和阻力指数的百分比变化始终显著相关（p<0.001）。在24小时结束时，这四种药物具有相同的降压效果，变化范围为14 - 17%。醋丁洛尔、阿替洛尔和普萘洛尔治疗使心脏指数恢复到对照值，而吲哚洛尔使心脏指数比治疗前值适度增加（13%，p<0.01）。使用所有四种药物时，心脏指数的二次升高与平均动脉压的下降呈负相关（p<0.001）。治疗后2小时血浆肾素被最大程度抑制，因此在醋丁洛尔、阿替洛尔和普萘洛尔引起平均动脉压发生任何变化之前。给药24小时后活性肾素的治疗前值与平均动脉压的降低在四组中的任何一组中均无相关性。尽管这四种药物具有“血管舒张”作用，但血浆去甲肾上腺素并未升高。我们的数据表明，β-肾上腺素能受体拮抗后血压下降时发生的主要血流动力学变化是血管舒张。血流的自动调节和肾素抑制均不能解释这种血管舒张作用。尽管血管舒张，但去甲肾上腺素没有增加，这表明β-肾上腺素能受体拮抗干扰了交感缩血管神经活动。这种效应可能解释了β-肾上腺素能受体拮抗剂的血管舒张和降压潜力。
