Sympathetic nervous activity may be augmented with the calcium channel blocker (CCB) treatment as a result of decreased blood pressure despite the advent of long-acting CCBs. A dihydropyridine CCB, cilnidipine blocks not only L type but also N type of calcium channels. Accordingly, we compared the effects of amlodipine and cilnidipine on autonomic nervous activity in hypertensive patients.
Eighteen hypertensive patients under the treatment of amlodipine monotherapy for at least 6 months were randomized to the 2 treatment arms. In 8 patients (70±9 (SD) years, 1 man and 7 women), amlodipine monotherapy was further continued for 6 months. In 10 patients (70±4 years, 3 men and 7 women), amlodipine treatment was switched to cilnidipine treatment. Before and after 6-month treatment with amlodipine or cilnidipine, each patient underwent 30 min resting electrocardiographic recording in the morning after an overnight fasting. By using spectral analysis of heart rate variability, frequency-domain measures were calculated. The low frequency (LF: 0.04 to 0.15 Hz)/high frequency (HF: 0.15 to 0.40 Hz) power ratio was used as an index of sympathovagal balance, and HF/total power (TP) ratio was used as an index of vagal activity. Plasma norepinephrine levels were measured by radioimmunoassay.
In patients with continuous amlodipine treatment, systolic and diastolic blood pressures (SBP, DBP) and heart rate (HR) remained unchanged. LF/HF and HF/TP ratios also remained unchanged (LF/HF 1.77±1.05 vs. 1.83±1.22, HF/TP 0.419±0.122 vs. 0.402±0.116). Plasma norepinephrine levels were comparable (370±88 pg/ml vs. 491±137 pg/ml). In patients switched to cilnidipine, SBP, DBP and HR were similar before and after switching. Interestingly, LF/HF ratio decreased significantly (p = 0.012) from 2.37±1.56 to 1.89±1.42, and HF/TP ratio increased significantly (p = 0.049) from 0.366±0.132 to 0.417±0.156, despite the comparable HR. Plasma norepinephrine concentrations decreased significantly (p = 0.009) from 359±65 pg/ml to 282±72 pg/ml.
These findings suggest that cilnidipine may provide beneficial prognosis for hypertensive patients because it suppresses sympathetic nervous activity.
1Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan
2Kyoto Prefectural University of Medicine, Kyoto, Japan
3Kitano Hospital, Tadukekofukai Medical Research Institute, Osaka, Japan