Ivabradine reversed nondipping heart rate in rats with l-NAME-induced hypertension.

We hypothesized that decreasing elevated night-time heart rate (HR) in hypertension by administering a bradycardic agent (ivabradine) at bedtime could bring cardiovascular benefit. Since rats are nocturnal animals, they exhibit circadian rhythms phase-shifted relative to humans. Sixty-six Wistar rats were divided into non-diseased controls and rats with l-NAME-induced hypertension to compare the haemodynamic effects of daytime-dosed and night-time-dosed ivabradine. l-NAME-induced hypertension inverted the physiological 5.6% night-to-day HR dip to an undesirable HR rise by 11.1%. Ivabradine dosed at daytime (the rat's resting phase) reverted a night-to-day HR rise to HR dip by 14.2%. These results suggest a cardiovascular benefit of ivabradine dosed at the human's resting phase (night-time) for hypertensive patients with nondipping HR.