Interactions between atrial natriuretic peptide and the renin–angiotensin system during salt-sensitivity exhibited by the proANP gene-disrupted mouse

Abstract

To understand the involvement of the systemic and cardiac components of the renin-angiotensin system (RAS) in the development of cardiac hypertrophy induced by salt intake, the present study analyzed the effect of high dietary salt (8.0% NaCl) in mice possessing a full complement (+/+) or ablation (-/-) of atrial natriuretic peptide (ANP). A 3 week treatment of 8.0% NaCl was able to induce cardiac hypertrophy in both genotypes, though exaggerated hypertrophy was noted in the ANP -/- mouse. Although a marked decrease in angiotensin II (Ang II) plasma levels in both genotypes fed a high salt diet was observed, systemic RAS mRNA components were altered only in the ANP-/- animals and remained unchanged in ANP+/+ mice. Decreased Ang II plasma levels were better correlated with decreases in angiotensinogen protein expression observed in both genotypes. High salt had no effect on cardiac RAS mRNA components in the ANP-/- animals, but did cause a significant decrease in some cardiac RAS mRNA components in ANP+/+ mice. As expected, high salt was able to increase plasma ANP levels and ventricular mRNA expression of ANP (ANP+/+ mice only) and B-type NP in both genotypes. The latter peptides are key cardiac markers of hypertrophy whose increased expression correlate well with the physical salt-induced cardiac alterations observed in this study. These findings suggest that although the RAS does not play a key role in salt-induced cardiac hypertrophy, ANP is an important determinant of the degree of salt-sensitivity observed in the proANP gene-disrupted animal.