Assessment of atrial natriuretic peptide resistance in cirrhosis with head-out water immersion and atrial natriuretic peptide infusion

Abstract

The nature of sodium retention in cirrhosis complicated by ascites has been studied for the last 30 years. Resistance to the natriuretic action of atrial natriuretic peptide (ANP) may play a potential role in this sodium retention. To further evaluate this possibility, we studied 12 patients with biopsy-proven cirrhosis and ascites on 2 consecutive days after a 7-day period off diuretics while receiving a 20 mmol/day sodium restricted diet. Following a crossover design, patients underwent head-out water immersion (HWI) for 3 h and were infused with a α-human ANP for 2 h on 2 consecutive days. Blood and urine samples were collected hourly. Five patients displayed a natriuretic response to HWI, sufficient to achieve negative sodium balance, and these patients were termed responders. Each of these five patients also displayed a natriuretic response to ANP infusion. In contrast, the other seven patients (nonresponders) consistently failed to develop a natriuretic response to either maneuver. The two groups had similar elevations in plasma ANP concentrations, but at baseline differed in terms of plasma sodium, plasma renin activity, and serum aldosterone. Despite higher serum aldosterone concentrations, nonresponders excreted less potassium than responders during the peak effect of the interventions, suggesting greater sodium delivery to the aldosterone-sensitive nephron segment in responders. We conclude that the inability to mount an adequate sodium excretory response to HWI in patients with cirrhosis may be conveyed through increased antinatriuretic factors that decrease the sodium delivery to the medullary collecting duct and inhibit the natriuretic effect of ANP at that site.Key words: atrial natriuretic peptide, cirrhosis, ascites, sodium.