Renal insensitivity to atrial natriuretic peptide in patients with cirrhosis and ascites. Effect of increasing systemic arterial pressure

The IV infusion of pharmacological doses (0.05 μg · kg^-1 · min^-1) of atrial natriuretic peptide to 16 patients with cirrhosis and ascites induced a significant increase in sodium excretion (65 ± 23 to 517 ± 231 μEq/min), urine volume (10.7 ± 2.3 to 15.7 ± 3.7 mL/min), and glomerular filtration rate (89 ± 4 to 110 ± 4 mL/min) in only 5 patients (responders). No significant changes in these parameters (15 ± 6 to 11 ± 4 μEq/min, 5.5 ± 1.0 to 4.2 ± 1.1 mL/min, and 81 ± 5 to 79 ± 6 mL/min, respectively) were observed in the remaining patients (nonresponders). Compared with responders, nonresponders had significantly lower baseline sodium excretion (P <0.02), urine flow (P <0.05), free water clearance (2.5 ± 0.9 vs. 6.9 ± 2.1 mL/min; P <0.05), and mean arterial pressure (82 ± 3 vs. 96 ± 2 mm Hg; P <0.01) and significantly higher plasma renin activity (16.3 ± 4.9 vs. 1.8 ± 0.2 ng · mL^-1 · h^-1; P <0.05) and aldosterone level (99 ± 24 vs. 13 ± 2 ng/dL; P <0.05). Atrial natriuretic peptide produced a similar reduction of arterial pressure in both groups. To investigate whether the blunted natriuretic response to atrial natriuretic peptide in nonresponders was caused by their lower arterial pressure, atrial natriuretic peptide was infused in 7 of these patients after increasing their arterial pressure to the levels of responders with norepinephrine. The increase in arterial pressure (from 81 ± 5 to 95 ± 5 mm Hg), which was not associated with significant changes in plasma renin activity and aldosterone concentration, did not reverse the blunted renal response to atrial natriuretic peptide in any of these patients. These results indicate that cirrhotic patients with blunted renal response to atrial natriuretic peptide are characterized by low arterial pressure, marked overactivity of the renin-aldosterone system, and severe sodium and water retention. Correction of hypotension without increasing effective blood volume does not restore renal insensitivity to atrial natriuretic peptide.