Autonomic Effects of Nebivolol versus Atenolol in Healthy Subjects

Abstract

Nitric oxide may stimulate sympathoinhibitory reflexes. Nebivolol is a beta(1) selective adrenergic receptor antagonist with ancillary vasodilating properties by modulating nitric oxide secretion. We investigated whether nebivolol affects autonomic function differently compared with atenolol, another selective beta(1)-blocker without vasorelaxant actions. Fourteen healthy volunteers (9 men, 5 women; 25 +/- 3.7 years) received single oral doses of 5 mg nebivolol, 50 mg atenolol, and 100 mg atenolol, each taken for a 2-week period. Heart rate variability (HRV) measurements in time- (SDNN; rMSSD; pNN50) and frequency-domain (low frequency-LF; high frequency-HF; LF/HF ratio) were used to study the autonomic effects of the three regimens on the same patients from serial 24-hour ECGs. Both nebivolol and atenolol, the 50 mg dose as well as the 100 mg dose, produced similar decreases in heart rate compared with baseline throughout the 24-h period (from 82 +/- 9 beats/min to 72 +/- 7 beats/min, 69 +/- 9, and 68 +/- 8 beats/min, respectively, p < 0.001). Overall, the administration of each beta -blocker led to directionally similar increases in the HRV variables, which were most significant following 100 mg atenolol. Nebivolol and the 50 mg dose of atenolol produced similar increases in rMSSD and pNN50 during the entire 24-h period, and in HF power, particularly during the nighttime (p < 0.05). However, the coefficient of HF variance resulted in similar values after either beta -blocker regimen. The LF/HF ratio was most reduced throughout the 24-h period following 100 mg atenolol (p < 0.001), and to a similar extent decreased in the nighttime following nebivolol and atenolol 50 mg (p < 0.01). Nebivolol 5 mg exerts similar effects on time and frequency domain indexes of HRV as 50 mg atenolol. Nebivolol attenuates sympathetic tone, but does not appear to promote vagal activity more than atenolol.