Expression of B-type natriuretic peptide in atrial natriuretic peptide gene disrupted mice

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are t wo hormones produced and secreted by the heart to control blood pressure, b ody fluid homeostasis and electrolyte balance. Each peptide binds to a comm on family of 3 receptors (GC-A, GC-B and C-receptor) with varying degrees o f affinity. The proANP gene disrupted mouse model provides an excellent opp ortunity to examine the regulation and expression of BNP in the absence of ANP. A new radioimmunoassay (RIA) was developed in order to measure mouse B NP peptide levels in the plasma, atrium and ventricle of the mouse. A detec tion limit of 3-6 pg/tube was achieved by this assay. Results show that pla sma and ventricular level of BNP were unchanged among the three genotypes o f mice. However, a significant decrease in the BNP level was noted in the a trium. The homozygous mutant (ANP-/-) had undetectable levels of BNP in the atrium, while the heterozygous (ANP+/-) and wild-type (ANP+/+) mice had 43 0 and 910 pg/mg in the atrium, respectively. Northern Blot analysis shows t he ANP-/- mice has a 40% reduction of BNP mRNA level in the atrium and a 5- fold increase in the ventricle as compared with that of the ANP+/+ mouse. O ur data suggest that there is a compensatory response of BNP expression to proANP gene disruption. Despite the changes in the atrial and ventricular t issue mRNA and peptide levels, the plasma BNP level remains unaltered in th e ANP-/- mice. We conclude that the inability of BNP to completely compensa te for the lack of ANP eventually leads to chronic hypertension in the proA NP gene disrupted mice.