Contribution of ANP to plasma protein escape during VE: effects of thiorphan and atrial appendectomy

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.