High levels of plasma atrial natriuretic peptides (ANP¹) are associated with pathological conditions such as congestive heart failure (CHF). Recently, we have identified a cardiac serine protease, corin, that is the pro-ANP convertase. In this study, we examine the regulation of corin gene expression in cultured hypertrophic cardiomyocytes and in the LV myocardium of a rat model of heart failure. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that both corin and ANP mRNA levels were significantly increased in phenylephrine (PE)-stimulated rat neonatal cardiomyocytes in culture. The increase in corin mRNA correlated closely with the increase in cell size and ANP mRNA expression in the PEtreated cells (r=0.95, p<0.01; r=0.92, p<0.01, respectively). The PE-treated cardiomyocytes had an increased activity in converting recombinant human pro-ANP to biologically active ANP, as determined by a pro-ANP processing assay and a cell-based cyclic guanosine monophosphate (cGMP) assay. In a rat model of heart failure induced by ligation of the left coronary artery, corin mRNA expression in the non-infarcted LV myocardium was significantly higher than that of control heart tissues from sham-operated animals, when examined by Northern blotting and RT-PCR at 8 weeks. These results indicate that the corin gene is up-regulated in hypertrophic cardiomyocytes and failing myocardium. Increased corin expression may contribute to elevation of ANP in the setting of cardiac hypertrophy and heart failure.