Blunted natriuretic response to low-dose brain natriuretic peptide infusion in nonazotemic cirrhotic patients with ascites and avid sodium retention.

Patients with cirrhosis and ascites have high plasma levels of atrial (ANP) and brain (BNP) natriuretic peptides, two cardiac hormones released by the atria and ventricles, respectively. We evaluated renal hemodynamics, sodium excretion, and intrarenal sodium handling (lithium clearance method) in seven cirrhotic patients with ascites and avid sodium retention before, during, and after the infusion of synthetic human BNP, at the dose of 4 pmol/kg.min for 1 hour, which has been shown to increase renal plasma flow, glomerular filtration rate (GFR), and sodium excretion in healthy subjects without affecting systemic hemodynamics. Plasma BNP levels were 7.31 +/- 0.85 pmol/L in baseline conditions, and increased to 33.60 +/- 2.96 pmol/L at the end of the infusion (P < .01 vs. baseline). Urinary excretion of guanosine 3',5'-cyclic monophosphate (cGMP) also significantly increased during the infusion, indicating stimulation of natriuretic peptide receptors by BNP. BNP administration did not modify renal plasma flow, GFR, sodium excretion or tubular sodium reabsorption to any appreciable extent. Arterial pressure heart rate, plasma norepinephrine, and plasma renin activity (PRA) where also unchanged, whereas plasma aldosterone concentration showed a significant, 35% reduction at the end of the postinfusion period, ruling out the possibility that BNP-induced vasodilation might be responsible for failure of the peptide to induce a natriuretic response. Overactivity of antinatriuretic factors is probably the main determinant of the blunted natriuretic effect of BNP in these patients.