Though increments in blood volume and atrial pressure are thought to be the primary stimuli for ANF secretion, plasma levels of this peptide do not always behave as a simple function of volume status. To outline the relationship between the latter and cardiac ANF release, we used five different volume-expansion protocols in anesthetized dogs. A stepwise expansion of plasma volume (PV) was achieved by two consecutive infusions: 0.9% saline followed or preceded by 4 or 25% bovine serum albumin (BSA), 4 or 25% dextran (Dx), or homologous plasma. Saline expansion led to a two- to four-fold increase in arterial plasma ANF level in all five protocols. Both 4 and 25% BSA caused no or very modest increase in plasma ANF, while all other colloid expanders caused the expected ANF release. In all protocols, plasma ANF closely correlated with central venous pressure (CVP). BSA expansion was the only protocol with no correlation between PV and ANF release. Changes in serum Ca2+ could not explain this finding. During BSA expansion, the lack of atrial response was related to the absence of increment (or even fall) in CVP despite the expanded PV. Similarly, urinary Na+ excretion was correlated both with CVP and ANF level but not with PV in BSA expansion. When the dogs were depleted of histamine before BSA infusion, the atrial secretory response was restored, suggesting that this colloid was associated with augmented capillary leakiness and vascular fluid efflux. These results show that the expansion of PV leads neither to ANF release nor to Na+ excretion if it is not accompanied by an expanded central blood volume with elevated atrial pressure.Key words: atrial natriuretic factor, volume expansion, isotonic saline, bovine serum albumin, dextran, homologous plasma.
