Originally, it was thought that ANP acted via GC-A-mediated cyclic GMP production in vascular smooth muscle cells [1,15,16]; however, studies in genetically engineered mice with cell type-specific deletion of GC-A have shown that mice with a smooth-muscle-cell-specific GC-A-knockout (SMC-GC-A-KO) do not exhibit hypertension [17], whereas mice with an endothelial-cell-specific GC-A-knockout (EC-GC-A-KO) do [18]. The gene discussed is GCA; the disease is Hypertension.