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
Objective: 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.
Design and Methods: 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.
Results: 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.
Conclusions: These findings suggest that cilnidipine may provide beneficial prognosis for hypertensive patients because it suppresses sympathetic nervous activity.