Cardiotrophin-1 (CT-1) a novel IL-6-related cytokine, induces distinct hypertrophic responses to endothelin-1 (ET-1) on cultured neonatal rat cardiac myocytes. We found that ET-1 and CT-1 show a distinct pattern of gene induction of natriuretic peptides. Elucidation of the transcriptional mechanisms of brain natriuretic peptide (BNP) gene induction by. ET-1 or CT-1 will provide better information for our understanding of the molecular mechanisms of cardiac hypertrophy. In this study, reporter constructs containing the human BNP 5' flanking sequence were transfected into neonatal rat cardiac myocytes and the cells were stimulated with ET-1 or CT-1. A total of 1813 bp of the human BNP 5' flanking sequence conferred an ET-1 inducibility on the reporter gene. However, it did not confer CT-1 inducibility. These results show that distinct mechanisms are involved in BNP gene induction by ET-1 or CT-1, and (in this study) that the CT-1 responsive element is not located in the region examined.