The relationship between plasma immunoreactive atrial natriuretic peptide (irANP) and radiolabeled albumin clearance (CBSA) in multiple tissues after graded volume stimuli was examined. To obtain a pure volume stimulus, pentobarbital sodium-anesthetized rats (5 or 6 per group) were equilibrated with a reservoir of blood by a femoral arteriovenous shunt, and volume expansion (VE) was produced by adjusting reservoir outflow. Peak increases in central venous pressure (CVP) during VE equal to 2 and 4% of the body weight over 5 min were 3.6 +/- 0.2 and 7.0 +/- 0.3 mmHg, and plasma irANP levels measured at 40 min post-VE were elevated 1.9- and 4.1-fold above baseline, respectively. Graded increases in CBSA measured between 5 and 35 min post-VE occurred in selective tissues, including intestine, visceral fat, lung, and muscle (P < or = 0.05). In separate animals, the level of VE was maintained after 2% VE by slower administration of an additional 2% VE for the remaining 30 min. This resulted in a more sustained CVP elevation and larger increases in irANP levels and CBSA compared with either 2 or 4% VE. Furthermore, equations derived from previous work in this laboratory involving intravenous administration of ANP predicted the magnitude of CBSA elevation during maintained VE. These findings support a role for ANP in regulating transcapillary protein distribution during acute intravascular expansion.