Indeed, mice with targeted disruption of BNP (Nppb-/- mice) display spontaneous development of cardiac fibrosis [35], whereas inactivation of ANP (Nppa gene) or natriuretic peptide receptor A (NPR-A, the principal receptor of ANP and BNP) have been documented to worsen hypoxia-induced cardiac hypertrophy in mice [36,37]. Here, NPPB is linked to cardiac hypertrophy.