SERUM-FREE CULTURE OF NEONATAL RAT CARDIAC MYOCYTES AND STUDY OF ENDOTHELIN-1 IN VITRO
1994 年 13 巻 2 号 p. 105-111
詳細
1994 年 13 巻 2 号 p. 105-111
To elucidate the mechanisms of cardiac myocyte cellular hypertrophy and induction of rhythmic contraction, we developed a serum-free culture system for neonatal rat cardiac myocytes. Cellular hypertrophy was elicited by a sympathetic hormone, norepinephrine (NE), phorbol-12,13-dibutyrate (PDBu), and serum. The hypertrophic effect. of NE was inhibited by prazocine, an acadrenergic receptor blocker. However, seruminduced hypertrophy was not inhibited by adrenergic receptor blockers. Hypertrophic stimulation induced by NE, PDBu and serum were inhibited by staurosporine, a protein kinase inhibitor, indicating that protein kinase C activation is involved in cardiac myocyte hypertrophy. Endothelin-1 (ET-1), a novel vasoconstrictor, also elicited cardiac myocyte cellular hypertrophy and strong rhythmic contraction. The cellular hypertrophy induced by ET-1 was also mediated by protein kinase C activation, because the effect was attenuated by H-7, a protein kinase C inhibitor. Conversely, ET-1-induced rhythmic contraction of cardiac myocytes was strongly attenuated by nicardipine, a calcium channel blocker. This indicates that extracellular calcium influx is required for contractile activation by ET-1. Interestingly, cardiac myocytes, which have been regarded as target cells of ET-1, are capable of synthesizing and secreting ET-1. This indicates that ET-1may act via an autocrine mechanism in the heart in some pathophysiological conditions.
