REVERSAL OF ATRIAL-NATRIURETIC-PEPTIDE RESISTANCE BY INCREASING DISTAL TUBULAR SODIUM DELIVERY IN PATIENTS WITH DECOMPENSATED CIRRHOSIS

To test the hypothesis that diminished sodium delivery to the distal t ubular site of atrial natriuretic peptide (ANP) action accounts for re nal ANP resistance in cirrhosis, 12 cirrhotic patients with ascites we re studied at baseline and during the infusion of ANP alone (0.15 mu g /kg/min), mannitol alone (4 g/hr), and ANP plus mannitol for 3 hours e ach. Distal tubular sodium delivery, as assessed by lithium clearance, was increased during the infusion of mannitol (13.8 +/- 3.4 to 23.7 /- 5.7 mL/min; P <.05) and during the ANP plus mannitol infusion (13.8 +/- 3.4 to 28.5 +/- 6.3 mL/min; P <.001) in 6 patients, subsequently termed ''responders.'' Both responders and nonresponders were resistan t to the natriuretic effect of ANP infused alone, and mannitol alone d id not produce an increase in urinary sodium excretion. However, in re sponders, the mannitol-induced increase in distal tubular sodium deliv ery resulted in a fivefold increase in urinary sodium excretion during ANP infusion (29 +/- 6 to 154 +/- 40 mu mol/min, P <.01). Urinary cyc lic guanosine monophosphate (cGMP) excretion increased significantly a nd to a similar extent during ANP and ANP plus mannitol in all 12 pati ents, supporting the active biological responsiveness of renal ANP rec eptors. Unlike respenders, nonresponders showed a significant decrease in arterial blood pressure and an increase in plasma renin activity d uring ANP plus mannitol, consistent with worsened arterial underfillin g caused by ANP-induced vasodilation. Thus, the present results suppor t the hypothesis that diminished distal tubular sodium delivery is a m ajor factor contributing to ANP resistance in cirrhosis.