Nieminen Tuomo, Ylitalo Ritva, Kööbi Tiit, Ylitalo Pauli, Kähönen Mika
Department of Pharmacological Sciences, Medical School, University of Tampere, Tampere (Finland).
Arzneimittelforschung. 2005;55(4):205-11. doi: 10.1055/s-0031-1296846.
To compare the acute effects of the beta-blocker propranolol (CAS 525-66-6), beta + alpha1-blocker carvedilol (CAS 72956-09-3) and alpha1-blocker tamsulosin (CAS 106463-17-6) on the cardiovascular responses to passive orthostasis.
The responses to passive orthostasis (tilt provocation at 60 degress for 8 min) were measured in normotensive healthy volunteers with finger-blood-pressure and whole-body impedance cardiography prior to drugs and three days after beginning the medications. The treatments were moderate oral doses of the beta-blocker propranolol HCl (40 mg twice daily, n = 7), (beta + alpha1-blocker carvedilol (12.5 mg once daily for two days and thereafter 25 mg daily, n = 7), alpha1-blocker tamsulosin HCl (0.4 mg once daily, n = 6), or placebo. The drugs were distributed in a randomised, double-blind fashion.
When measured prior to the head-up tilt test, propranolol and carvedilol had decreased supine systolic arterial pressure (SAP) more than placebo, and heart rate (HR) more than placebo and tamsulosin. Propranolol had decreased also pulse wave velocity more than placebo. The cardiac index (CI), stroke index (SI) and systemic vascular resistance index (SVRI) were not changed with any drugs. During the head-up tilt, tamsulosin decreased SAP and SVRI and augmented CI but not SI. The SVRI response curve with tamsulosin differed from that with propranolol or carvedilol. Also, tamsulosin increased HR compared to the beta-blocking drugs. The propranolol and carvedilol groups did not differ from each other in terms of any parameter.
Tamsulosin significantly decreases SAP in the passive head-up tilt, indicating that it is not purely uroselective alpha1-blocker. The responses with tamsulosin clearly differ from those with propranolol and carvedilol, the responses with the latter two being practically equal.
比较β受体阻滞剂普萘洛尔(化学物质登记号525 - 66 - 6)、β + α1受体阻滞剂卡维地洛(化学物质登记号72956 - 09 - 3)和α1受体阻滞剂坦索罗辛(化学物质登记号106463 - 17 - 6)对被动直立位心血管反应的急性影响。
在血压正常的健康志愿者中,于用药前及开始用药三天后,通过手指血压测量和全身阻抗心动图测量对被动直立位(60度倾斜激发8分钟)的反应。治疗采用中等口服剂量的β受体阻滞剂盐酸普萘洛尔(40毫克,每日两次,n = 7)、β + α1受体阻滞剂卡维地洛(12.5毫克,每日一次,连用两天,此后每日25毫克,n = 7)、α1受体阻滞剂盐酸坦索罗辛(0.4毫克,每日一次,n = 6)或安慰剂。药物以随机、双盲方式分配。
在头高位倾斜试验前测量时,普萘洛尔和卡维地洛使仰卧位收缩压(SAP)降低的幅度大于安慰剂,使心率(HR)降低的幅度大于安慰剂和坦索罗辛。普萘洛尔使脉搏波速度降低的幅度也大于安慰剂。任何药物均未改变心脏指数(CI)、每搏指数(SI)和全身血管阻力指数(SVRI)。在头高位倾斜期间,坦索罗辛降低了SAP和SVRI并增加了CI,但未增加SI。坦索罗辛的SVRI反应曲线与普萘洛尔或卡维地洛的不同。此外,与β受体阻滞剂相比,坦索罗辛增加了HR。普萘洛尔组和卡维地洛组在任何参数方面均无差异。
坦索罗辛在被动头高位倾斜时显著降低SAP,表明它并非纯粹的尿道选择性α1受体阻滞剂。坦索罗辛的反应与普萘洛尔和卡维地洛的明显不同,后两者的反应基本相同。