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双醋洛尔与普萘洛尔对健康志愿者静息及运动时全身和局部血流动力学影响的比较。

Comparison of the effects of dilevalol and propranolol on systemic and regional haemodynamics in healthy volunteers at rest and during exercise.

作者信息

Bellissant E, Annane D, Thuillez C, Giudicelli J F

机构信息

Service de Pharmacologie Clinique, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.

出版信息

Eur J Clin Pharmacol. 1994;47(1):39-47. doi: 10.1007/BF00193476.

Abstract

The effects of single oral doses of dilevalol 400 mg and propranolol 80 mg on systemic and regional haemodynamics at rest and after sub-maximal exercise, were compared, in a placebo-controlled, randomised, double-blind, crossover study in 6 healthy male volunteers. At rest, as compared to placebo, neither dilevalol nor propranolol significantly affected arterial pressure and heart rate but, whereas propranolol decreased cardiac output (-27% at 2 h) and tended to increase total peripheral resistance, dilevalol tended to increase cardiac output and decreased total peripheral resistance (-7% at 2 h). Neither dilevalol nor propranolol affected brachial artery diameter. Propranolol tended to decrease brachial artery flow (-20% at 2 h) and to increase brachial vascular resistance (+25% at 2 h), but dilevalol did not and the brachial irrigation ratios did not change. Neither of the drugs affected carotid haemodynamics or plasma atrial natriuretic factor. Both drugs tended to decrease plasma renin activity, and dilevalol (+82% at 2 h) increased norepinephrine more than propranolol (+19% at 2 h). After exercise, dilevalol and propranolol produced similar falls in the induced increases in arterial pressure, heart rate and cardiac output, and had the same effects on regional haemodynamics, plasma renin activity and atrial natriuretic factor. Finally, dilevalol greatly increased plasma norepinephrine. We conclude that the beta 2-adrenoceptor agonist activity of dilevalol was clearly expressed at rest, thus inducing vasodilation and counteracting the beta-adrenoceptor blockade-induced negative chronotropic and inotropic effects. However, during sub-maximal exercise, only the beta-adrenoceptor antagonist activity of dilevalol was apparent.

摘要

在一项针对6名健康男性志愿者的安慰剂对照、随机、双盲、交叉研究中,比较了单次口服400毫克双醋洛尔和80毫克普萘洛尔对静息及次极量运动后全身和局部血流动力学的影响。静息时,与安慰剂相比,双醋洛尔和普萘洛尔均未显著影响动脉压和心率,但普萘洛尔降低心输出量(2小时时降低27%)并倾向于增加总外周阻力,而双醋洛尔倾向于增加心输出量并降低总外周阻力(2小时时降低7%)。双醋洛尔和普萘洛尔均未影响肱动脉直径。普萘洛尔倾向于降低肱动脉血流(2小时时降低20%)并增加肱血管阻力(2小时时增加25%),但双醋洛尔未产生此影响,肱灌注率也未改变。两种药物均未影响颈动脉血流动力学或血浆心钠素。两种药物均倾向于降低血浆肾素活性,且双醋洛尔(2小时时增加82%)比普萘洛尔(2小时时增加19%)更能增加去甲肾上腺素。运动后,双醋洛尔和普萘洛尔在使动脉压、心率和心输出量的诱发性增加下降方面效果相似,且对局部血流动力学、血浆肾素活性和心钠素具有相同影响。最后,双醋洛尔大幅增加血浆去甲肾上腺素。我们得出结论,双醋洛尔的β2 -肾上腺素能受体激动剂活性在静息时明显表现出来,从而诱导血管舒张并抵消β -肾上腺素能受体阻断引起的负性变时和变力作用。然而,在次极量运动期间,双醋洛尔仅表现出β -肾上腺素能受体拮抗剂活性。

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