Possible involvement of endothelin-1 in cardioprotective effects of benidipine.
Benidipine hydrochloride has been developed as an antagonist for the L-type calcium channel and is used as an anti-hypertensive drug. But recent studies have reported that benidipine exerts not only antihypertensive actions but also anti-hypertrophic actions on cardiac muscles. Endothelin-1 (ET-1), one of the endogenous pathological humoral factors of cardiovascular diseases such as hypertension and heart failure, has a strong vasoconstrictive action and could induce hypertension and cardiac hypertrophy. So, it is a matter of great interest whether or not calcium antagonists can decrease cardiac hypertrophy induced by the pathological vasoactive substances such as ET-1. Thus, the present study was designed to elucidate the effects of benidipine on cardiac hypertrophy, and particularly on the interaction with ET-1, using neonatal rat cardiac myocytes (MCs) and cardiac non-myocytes (NMCs) culture systems. Cells were cultured with or without ET-1, benidipine, and nifedipine and the effects of calcium antagonists on cardiac hypertrophy were evaluated by incorporations of [3H]-leucine and [3H]-thymidine into MCs and/or NMCs. Benidipine significantly decreased the ET-1-induced increase of [3H]-leucine and [3H]-thymidine uptake into cardiac MCs and NMCs, whereas no significant effects of nifedipine were observed. Furthermore, benidipine (10(-8)M) attenuated ET-1 secretions from NMCs. In summary, benidipine at least partially decreased the cardiac hypertrophy induced by paracrine mechanisms through its attenuation of ET-1 secretions from NMCs. Benidipine could thus be a useful tool for preventing cardiac hypertrophy due to hypertension.
Ikeda
K
K
Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Tojo
K
K
Tokudome
G
G
Akashi
T
T
Hosoya
T
T
Harada
M
M
Nakagawa
O
O
Nakao
K
K
D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006332:Cardiomegaly / Q000188:drug therapy; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology*; D019332:Endothelin-1 / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy; D007930:Leucine / Q000493:pharmacokinetics; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000166:cytology*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D019332:Endothelin-1; D014316:Tritium; C061004:benidipine; D007930:Leucine; D009543:Nifedipine; D013936:Thymidine