Hypotension and Renal Impairment during Infusion of Atrial Natriuretic Factor in Liver Cirrhosis with Ascites

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Abstract
Plasma immunoreactive atrial natriuretic factor (irANF) levels and the effects of α-human ANF (α-hANF) infusion were investigated in 7 patients with liver cirrhosis and ascites. Under basal conditions, supine blood pressure (BP) averaged 136/76 ± 9/4 mm Hg (mean ± SEM). Plasma irANF concentrations (124 ± 33pg/ml)were higher (p < 0.01) than those in age-matched normal subjects (47 ± 5 pg/ml). Plasma renin activity (PRA 5.9 ± 2.2 ng/ml/h), aldosterone (18 ± 7 ng/dl) and norepinephrine (NE, 66 ± 5 ng/dl) levels were also elevated compared to the age-related normal range. α-hANF infusion for 60 min at 0.036 μg/kg/min decreased the mean BP (-14%; p < 0.05), increased PRA (+179%; p < 0.05) and plasma NE (+24%; p < 0.05). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), diuresis and natriuresis were not modified. A subsequent 60-min infusion of α-hANF at 0.067 μg/kg/min produced a marked fall in mean BP (-26%; p < 0.001), hemoconcentration (hematocrit + 6%; p < 0.001) despite stable body fluid balance and a further increase in PRA (+350%, p < 0.005). GFR and ERPF were severely reduced (-55 and -56%, respectively; p < 0.001), while diuresis and natriuresis were not modified. Plasma aldosterone was unaltered during, but rose (+72%; p < 0.01) after the cessation of α-hANF infusion. Variations in natriuresis during α-hANF infusion correlated positively with BP (r = 0.47; p < 0.01), ERPF (r = 0.53; p < 0.01) or GFR (r = 0.51; p < 0.01). These findings indicate that in patients with liver cirrhosis and ascites, plasma levels of circulating irANF are increased. Infusion of α-hANF in pharmacological doses can produce unwanted falls in BP, ERPF and GFR which, in turn, preclude a therapeutically desired renal excretory response.