The atrial natriuretic peptide hormonal system is altered to a variable degree in patients with cirrhosis. Portal pressure and portal-systemic shunting are also varied in cirrhosis. We used a portal vein-ligated rat model with predictable portal hypertension to study the effects of portal hypertension alone on the atrial natriuretic peptide hormonal system. Sham-operated rats were used as controls. Mean portal pressure was significantly increased in portal vein-ligated rats (portal vein-ligated rats, 21.7 +/- 0.74 cm H2O; sham-operated rats, 13.7 +/- 0.47 cm H2O; p less than 0.0001). Plasma atrial natriuretic peptide decreased 50% in the portal vein-ligated rats (p less than 0.0001). Atrial natriuretic peptide messenger RNA level was decreased by 40% to 60% in the left and right atria and in the ventricles of portal vein-ligated rats (p less than 0.05 for each chamber). Only one class of glomerular binding site was identified by competitive binding studies. The atrial natriuretic peptide glomerular receptor density increased in the portal vein-ligated rats (portal vein-ligated rats, 1,660 +/- 393; sham-operated 725 +/- 147 fmol/mg protein, p less than 0.02), whereas affinity decreased (portal vein-ligated, 1.69 +/- 0.49; sham-operated, 0.55 +/- 0.12 nmol/L, p less than 0.02). No difference was seen in the amount of cyclic GMP generated by atrial natriuretic peptide stimulation in isolated glomeruli from portal vein-ligated and sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)