Possible involvement of endothelin-1 in cardioprotective effects of benidipine.

Abstract

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.

• Authors: K Ikeda, K Tojo, G Tokudome, T Akashi, T Hosoya, M Harada, O Nakagawa, K Nakao
• Journal: Hypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 23 Issue 5 Pg. 491-6 (Sep 2000) ISSN: 0916-9636 [Print] England
• PMID: 11016804 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Blockers
• Dihydropyridines
• Endothelin-1
• Tritium
• benidipine
• Leucine
• Nifedipine
• Thymidine

Topics

• Animals
• Animals, Newborn
• Calcium Channel Blockers (pharmacology)
• Cardiomegaly (drug therapy)
• Cells, Cultured
• Dihydropyridines (pharmacology)
• Endothelin-1 (pharmacology)
• Hypertension (drug therapy)
• Leucine (pharmacokinetics)
• Muscle Fibers, Skeletal (cytology, drug effects, metabolism)
• Myocardium (cytology)
• Nifedipine (pharmacology)
• Rats
• Rats, Wistar
• Thymidine (pharmacokinetics)
• Tritium