The significance of amlodipine on autonomic nervous system adjustment (ANSA method): a new approach in the treatment of hypertension.
BACKGROUND
Cardiovascular autonomic modulation is altered in patients with essential hypertension.


OBJECTIVE
To evaluate acute and long-term effects of amlodipine on cardiovascular autonomic function and haemodynamic status in patients with mild essential hypertension.


METHODS
Ninety patients (43 male, mean age 52.12 +/- 10.7) years with mild hypertension were tested before, 30 minutes after the first 5 mg oral dose of amlodipine and three weeks after monotherapy with amlodipine. A comprehensive study protocol was done including finger blood pressure variability (BPV) and heart rate variability (HRV) beat-to-beat analysis with impedance cardiography, ECG with software short-term HRV and nonlinear analysis, 24-hour Holter ECG monitoring with QT and HRV analysis, 24-hour blood pressure (BP) monitoring with systolic and diastolic BPV analysis, cardiovascular autonomic reflex tests, cold pressure test, mental stress test. The patients were also divided into sympathetic and parasympathetic groups, depending on predominance in short time spectral analysis of sympathovagal balance according to low frequency and high frequency values.


RESULTS
We confirmed a significant systolic and diastolic BP reduction, and a reduction of pulse pressure during day, night and early morning hours. The reduction of supraventricular and ventricular ectopic beats during the night was also achieved with therapy, but without statistical significance. The increment of sympathetic activity in early phase of amlodipine therapy was without statistical significance and persistence of sympathetic predominance after a few weeks of therapy detected based on the results of short-term spectral HRV analysis. All time domain parameters of long-term HRV analysis were decreased and low frequency amongst spectral parameters. Amlodipne reduced baroreflex sensitivity after three weeks of therapy, but increased it immediately after the administration of the first dose.


CONCLUSIONS
The results of the study showed that amlodipine affected autonomic modulation as a shift to sympathetic hyperactivity, but without statistical significance. In the selected group of patients with vagal predominance in sympathovagal balance, amlodipine increased sympathetic and decreases vagal activity. Therefore we conclude that amlodipine mostly exerts impact on autonomic function modulation in patients with vagal predominance in resting state.
Milovanović
Branislav
B
Department of Cardiology, Neurocardiology Laboratory, Clinical Hospital Centre "Bezanijska kosa", Belgrade, Serbia. branislav_milovanovic@vektor.net
Trifunović
Danijela
D
Milićević
Nebojsa
N
Vasić
Karin
K
Krotin
Mirjana
M
D017311:Amlodipine / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001341:Autonomic Nervous System / Q000187:drug effects*; D017704:Baroreflex; D015716:Electrocardiography, Ambulatory; D005260:Female; D006321:Heart / Q000294:innervation*; D006339:Heart Rate; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged
D000959:Antihypertensive Agents; D017311:Amlodipine