Nitric Oxide Inhibits Endothelin-1-Induced Cardiomyocyte Hypertrophy through cGMP-mediated Suppression of Extracellular-Signal Regulated Kinase Phosphorylation

Cardiac hypertrophy is a compensatory mechanism in re-sponse to a variety of cardiovascular diseases. Recently, reac-tive oxygen species and nitric oxide (NO) have been demon-strated to be involved in the pathogenesis of atherosclerosis; however, the role of these free radicals in the development of cardiac hypertrophy remains unclear. In this study, we investi-gate NO modulation of cellular signaling in endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy in culture. ET-1 treatment of cardiomyocytes increased constitutive NO synthase activity and induced NO production via the stimulation of ET-receptor subtype ETB. Using Northern blot analysis and chloramphenicol acetyltransferase assay, we found that NO suppressed the ET-1-induced increase in c-fos mRNA level and promoter ac-tivity. In contrast, ET-1 stimulation of c-fos expression wa