LOW-OXYGEN ENHANCES ENDOTHELIN-1 (ET-1) PRODUCTION AND RESPONSIVENESS TO ET-1 IN CULTURED CARDIAC MYOCYTES

To understand the pathophysiological role of ET-1 in heart, the ET-1 production ability and the responsiveness to ET-1 in cultured neonatal rat cardiac myocytes were compared between high (50%) and low (21%) oxygen atmosphere culture conditions. The amount of immunoreactive ET-1 secreted by the cardiac myocytes into the culture medium was much higher at the low oxygen condition. An analysis of ET-1 binding capacity to the cardiac myocytes revealed that the receptor number of ET-1 was about two-fold at low oxygen culture condition. In fact, an addition of ET-1 (1nM) increased in protein synthesis at the low but not the high oxygen culture condition. Thus, the increase in ET-1 production and responsiveness to ET-1 in the cardiac myocytes at the low oxygen culture condition suggests that autocrine ET-1 might be involved in the maintenance of beating ability in heart at hypoxia. (C) 1994 Academic Press, Inc.