Cardioprotective effect of an L/N-type calcium channel blocker in patients with hypertensive heart disease.
BACKGROUND
Left ventricular (LV) diastolic dysfunction is related to increased cardiac sympathetic activity. We investigated the effect of cilnidipine, an L/N-type calcium channel blocker, on LV diastolic function and cardiac sympathetic activity in patients with hypertensive heart disease (HHD) using radionuclide myocardial imaging.


RESULTS
Thirty-two frame electrocardiography (ECG) -gated (99m)Tc-sestamibi (MIBI) myocardial single photon emission computed tomography (SPECT), and (123)I-metaiodobenzylguanidine (MIBG) imaging were performed before and 6 months after drug administration in 32 outpatients with HHD. Sixteen of the patients were treated with cilnidipine and the other 16 were treated with nifedipine retard. The parameters for assessing LV diastolic function evaluated using ECG-gated (99m)Tc-MIBI SPECT were peak filling rate (PFR), first-third filling rate (1/3FR), and time to peak filling (TPF). Cardiac sympathetic activity was assessed as early and delayed heart to mediastinum (H/M) ratios and a washout rate (WR), using (123)I-MIBG imaging. The PFR and 1/3FR significantly increased after 6 months of treatment with cilnidipine (p<0.05 for both), but did not with nifedipine retard. The H/M ratios significantly increased (p<0.05 for both) in conjunction with a decreased WR (p<0.05) in the cilnidipine group. Moreover, a significant positive correlation was seen between the rate of change in PFR and the rate of change in early and delayed H/M ratios in the cilnidipine group (p<0.05 for both). The same results were obtained for the relationship between the rate of change in 1/3FR and the rate of change in H/M ratios (p<0.05 for both). However, no such relationship was seen in the nifedipine group.


CONCLUSIONS
These data indicate that cilnidipine seems to suppress cardiac sympathetic overactivity via blockade of N-type calcium channels and improves LV diastolic function in patients with HHD.
Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. kosaka@doc.med.akita-u.ac.jp
Toshimitsu
T
Kosaka
Masayasu
M
Nakagawa
Masaru
M
Ishida
Kenji
K
Iino
Hiroyuki
H
Watanabe
Hitoshi
H
Hasegawa
Hiroshi
H
Ito
D000328:Adult; D000368:Aged; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D004095:Dihydropyridines / Q000008:administration & dosage*; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging / Q000294:innervation; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009529:Nicardipine / Q000008:administration & dosage; D011446:Prospective Studies; D013564:Sympathetic Nervous System / Q000503:physiopathology; D015899:Tomography, Emission-Computed, Single-Photon; D016277:Ventricular Function, Left
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C065927:cilnidipine; D009529:Nicardipine