Studies using gene disruption of Nppa (coding pro-ANP) and Nppb (coding for pro-BNP) have shown that ANP- and BNP-deficient genetic strains of mice exhibit a defect in ANP and BNP synthesis that can cause hypertension and cardiovascular dysfunction in homozygous null mutant mice with no circulating or cardiac ANP and BNP, respectively [80,81]. This evidence concerns the gene NPPA and hypertensive disorder.