The aim of this study was to investigate whether C‐ANP4‐23, a natriuretic peptide receptor‐C (NPR‐C) ligand that was shown to inhibit vasoactive peptide‐induced enhanced protein synthesis in A10 VSMC could also attenuate hypertrophy of VSMC isolated from rat model of cardiac hypertrophy and to further explore the possible involvement of Gqα/PLCβ1 proteins and ROS‐mediated signaling in this effect. This evidence concerns the gene NPR3 and cardiac hypertrophy.