Effects of High Dose Atrial Natriuretic Peptide on Renal Haemodynamics, Sodium Handling and Hormones in Cirrhotic Patients with and Without Ascites

Abstract

To elucidate and to try to reverse the antinatriuretic mechanisms in liver cirrhosis, atrial natriuretic peptide (ANP) was given as a pharmacological bolus dose (2 µg per kg body weight) to 14 cirrhotic patients, and as a control to 14 healthy subjects. The nine patients with ascites had baseline values of glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and blood pressure (BP) similar to controls. Their distal tubular fractional reabsorption of sodium (DFR_Na), estimated by the lithium clearance technique, was higher than in controls, and so were plasma values of aldosterone (564 vs. 119 pmol 1⁻¹ medians), endothelin (1.23 vs. 0.63 pmol 1⁻¹), ANP (7.5 vs. 3.6 pmol 1⁻¹) and cyclic GMP (8.8 vs. 4.6 nmol 1⁻¹); p<0.01 for all. The five patients without ascites had higher GFR and ERPF, and lower plasma angiotensin II than controls. After ANP injection, similar plasma levels of ANP and cyclic GMP were reached in all groups. Urinary sodium excretion rate increased in controls (0.23 to 0.52 mmol min⁻¹, p<0.01), while GFR increased (108 to 117 ml min⁻¹, p<0.05), and DFR_Na decreased (93 to 89%, p<0.01). In cirrhotics with ascites sodium excretion was unaltered (0.12 to 0.11 mmol min⁻¹), and so was GFR (84 to 83 ml min⁻¹). Proximal tubular fractional reabsorption of sodium increased after 90 min, whereas DFR_Na decreased immediately (97 to 96%, p<0.01) though less markedly than in controls. Sodium excretion increased in four of five patients without ascites (0.23 to 0.27 mmol min⁻¹, medians). In patients with ascites, endothelin in plasma decreased after ANP (p<0.05). Plasma levels of angiotensin II, aldosterone and vasopressin were unchanged in all groups.

In conclusion, although hyper-reabsorption of sodium occurred in the distal rather than the proximal part of the nephron in cirrhotic patients with ascites, ANP had no natriuretic effect. This was most probably due primarily to the lack of increase of GFR and blunted inhibition of DFR_Na, attributed to high aldosterone. The effect of ANP in suppressing the high endothelin did not seem to improve sodium excretion.

Key Words:

• Aldosterone
• atrial natriuretic peptide
• blood pressure
• cirrhosis
• endothelin
• lithium
• renal function