Additive and synergistic interaction of atrial natriuretic peptide and volume expansion

To investigate whether atrial natriuretic peptides (ANP) are entirely responsible for the natriuresis of volume expansion (VE), we studied the natriuresis from acutely snared and nonsnared kidneys of rats undergoing sustained saline VE and subsequent infusion of maximal doses of ANP (atriopeptin II), or vice versa. Fractional excretion of Na (FENa) was increased from control (0.15 +/- 0.03%) to 4.6 +/- 0.6% by VE and to 10.9 +/- 1.5% by subsequent ANP infusion. With ANP alone FENa increased from control (0.24 +/- 0.04%) to 2.6 +/- 0.3%, and to 10.8 +/- 0.9% with VE, showing additive effects by both. Natriuresis with VE was significantly greater than with ANP alone (P less than 0.01) and both exhibited synergism, producing significantly greater natriuresis in the presence of the other than alone (P less than 0.05 for both). A reduction in perfusion pressure inhibited the effects of ANP and reduced that of VE. Natriuresis was produced by ANP independently of changes in glomerular filtration rate. It is concluded that 1) VE and ANP produce natriuresis by different renal mechanisms and that therefore, ANP can only account for part of the natriuresis of sustained VE; 2) the two have a synergistic interaction on natriuresis, probably through an intrarenal mechanism.