Effect of the renin-angiotensin system or calcium channel blockade on the circadian variation of heart rate variability, blood pressure and circulating catecholamines in hypertensive patients

J Hypertens. 2005 Jun;23(6):1251-60. doi: 10.1097/01.hjh.0000170389.69202.53.


Objective: To determine the effects of 8 weeks of therapy with amlodipine, ramipril or telmisartan on the autonomic system over 24 h in hypertensives.

Methods: After a placebo run-in, 57 patients were included in a prospective randomized open-label design protocol for therapy with amlodipine (5 mg for 4 weeks followed by 10 mg for 4 weeks, n = 22), or ramipril (2.5 mg for 1 week, 5.0 mg for 3 weeks and 10 mg for 4 weeks, n = 17) or telmisartan (80 mg for 8 weeks, n = 18). Autonomic functions were assessed by norepinephrine (NE) and epinephrine (E), as well as by the spectral analysis of heart rate variability (HRV).

Results: The 24-h ambulatory blood pressure, plasma NE and HRV demonstrated the characteristic day-night circadian rhythm in hypertensives. Higher values for SBP and DBP and for NE levels, as well as for spectral analysis components - low frequency band (LF) and low frequency/high frequency (LF/HF) ratio - were found during the day, whereas the HF was higher during the night. In patients treated with amlodipine, the HF decreased significantly during the night, while the LF and the LF/HF ratio increased during the day in association with the rise in NE. The therapy with telmisartan did increase the HF during the night and the day, while ramipril did not influence all HRV components during the night but significantly increased the HF, and decreased the LF/HF ratio during the day. No changes were observed in plasma NE with telmisartan or ramipril, but a 50% increase in NE levels throughout the 24-h period was found in amlodipine-treated patients.

Conclusion: These data suggest a sympathetic activation during the day and a decrease in parasympathetic activity during the night after therapy with amlodipine, correlated with increases in plasma NE. In contrast, the therapy with telmisartan significantly increased parasympathetic activity without changes in NE during the night and day. The therapy with ramipril increased the parasympathetic activity only during the day.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amlodipine / administration & dosage*
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
  • Benzimidazoles / administration & dosage
  • Benzoates / administration & dosage
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / administration & dosage*
  • Circadian Rhythm
  • Epinephrine / blood
  • Female
  • Heart Rate / drug effects
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Norepinephrine / blood
  • Ramipril / administration & dosage*
  • Renin-Angiotensin System / drug effects
  • Telmisartan
  • Treatment Outcome


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Benzimidazoles
  • Benzoates
  • Calcium Channel Blockers
  • Amlodipine
  • Ramipril
  • Telmisartan
  • Norepinephrine
  • Epinephrine