Beneficial effects of the dual L- and T-type Ca2+ channel blocker efonidipine on cardiomyopathic hamsters.
BACKGROUND
The T-type Ca2+ channel (TCC) is activated, and abnormalities of the TCC may be related to the pathogenesis of Ca2+ overload, in cardiomyopathic hamster hearts. The aims of the present study were to investigate the alteration in expression of the TCC and to examine the effects of a dual L-and T-type Ca2+ channel blocker, efonidipine (EFO), on cardiac function and TCC during development of heart failure in UM-X7.1 cardiomyopathic hamsters.


RESULTS
UM-X7.1 and golden hamsters were examined, and EFO was administered at the age of 20 weeks for 4 weeks. Cardiac function was examined, the expression of TCCalpha1G was measured, and ventricular myocytes were subjected to a patch-clamp study. At 24 weeks, vehicle-treated UM-X7.1 hamsters exhibited significant increases in left ventricular (LV) size, with marked decreases in ejection fraction (LVEF) compared with golden hamsters. In the UM-X7.1 group, the expression of TCCalpha1G increased during development of heart failure compared with the golden hamster group. In the UM-X7.1 group, EFO treatment significantly attenuated the decrease of LVEF without affecting blood pressure compared with the vehicle group. EFO treatment decreased heart rate (by approximately 10%) in both groups. In the golden hamster group, EFO treatment did not affect LV function. The TCC current in ventricular myocytes was significantly increased in UM-X7.1, and was inhibited by EFO in a dose-dependent manner.


CONCLUSIONS
In cardiomyopathic hamster hearts, abnormalities in the TCC may be at least in part related to the pathogenesis of abnormal Ca2+ homeostasis, and TCC-blocker treatment may decrease the TCC current, resulting in an improvement of cardiac function. TCC blocker therapy might be a new strategy for certain types of heart failure.
Suzuki
Shinsuke
S
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Ohkusa
Tomoko
T
Ono
Katsushige
K
Sato
Takashi
T
Yoshida
Masa-aki
MA
Yano
Masafumi
M
Takebayashi
Satoshi
S
Matsuzaki
Masunori
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000378:metabolism*; D009202:Cardiomyopathies / Q000378:metabolism* / Q000503:physiopathology; D006224:Cricetinae; D004095:Dihydropyridines / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D008647:Mesocricetus; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009596:Nitrophenols / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018408:Patch-Clamp Techniques
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D020097:Natriuretic Peptide, Brain; C066425:efonidipine