Effect of morning and bedtime dosing with cilnidipine on blood pressure, heart rate, and sympathetic nervous activity in essential hypertensive patients

Cilnidipine has a blocking action against N-type calcium channels as well as L-type calcium channels. We studied the effect of morning and bedtime dosing on circadian variation of blood pressure (BP), heart rate (HR), and activity of the autonomic nervous system, using an open randomized crossover study in 13 essential hypertensive patients. An automated device allowed 24-hour monitoring of ambulatory BP and HR and the power spectrum of the R-R interval, at the observation period, the morning dosing regimen, and the bedtime dosing regimen. Morning dosing and bedtime dosing with cilnidipine reduced the average systolic BP over 24 hours, during daytime, and during nighttime. The average HR and the average LF/HF ratio over 24 hours, during daytime, and during nighttime, were similar for the three periods. Both morning and bedtime dosing reduced the maximum systolic BP in the early morning and suppressed the morning rise of BP, which were accompanied by partial inhibition of the increase in LF/HF ratio. Our results show that cilnidipine administered once daily is an efficient antihypertensive drug regardless of the time of dosing, without reflex tachycardia and increase in sympathetic nervous activity, and with partial inhibition of the morning activation of the sympathetic nervous system.