The effects of endopeptidase inhibition and right atrial appendectomy (AA) on 
plasma immunoreactive atrial natriuretic peptide (irANP) concentrations and 
extravascular accumulation of 131I-labeled bovine serum albumin (CBSA) during 
volume expansion (VE) were examined in pentobarbital sodium-anesthetized rats (n 
= 5 per group). Compared with controls, infusion of isoncotic albumin (30 ml/kg) 
increased central venous pressure (CVP) by 5.5 mmHg, plasma irANP by 7-fold, and 
CBSA in multiple tissues by 1.6- to 4-fold (P < or = 0.05). Inhibition of ANP 
metabolism with thiorphan (40 mg/kg) had no effect in control animals but 
increased plasma irANP (+118%) and CBSA (+30-100%) compared with VE alone (P < 
or = 0.05). Likewise, interference with ANP release by AA reduced plasma irANP 
(-80%) and CBSA (-30 to -80%) response to VE in parallel (P < or = 0.05). The 
peak increase in CVP during VE was not affected by either of these 
manipulations. It is concluded that endogenous ANP increases plasma protein 
extravasation independent of volume and pressure disturbances during acute 
intravascular expansion.