Serum and urinary nitrate levels in liver cirrhosis: endotoxemia, renal function and hyperdynamic circulation

The relationship between nitric oxide production, endotoxemia, renal function and hyperdynamic circulatory syndrome has not been yet investigated in patients with cirrhosis.

Serum and urine nitrate, endotoxemia and cardiac index were measured in 59 patients with cirrhosis.

Patients with a tense ascites had higher serum nitrate levels than healthy control subjects (39 +/- 7 vs 19 +/- 4 mumol/l, p < 0.01). Patients with mild ascites and without ascites had normal values of nitrate levels. In the group of patients not treated with diuretics (n = 38), creatinine and nitrate clearances were lower in ascitic patients than in nonascitic patients (respectively 0.82 +/- 0.12 vs 1.48 +/- 0.32 ml/s, p < 0.02 and 0.30 +/- 0.07 vs 2.89 +/- 2.04 ml/s, p < 0.05). Endotoxin levels were higher in patients with cirrhosis than in control subjects and paralleled the severity of liver failure (Child A/B/C vs control subjects: 0.056 +/- 0.014/0.064 +/- 0.005/ 0.090 +/- 0.008 vs 0.027 +/- 0.005 Endotoxin Units/ml, p < 0.001). Serum nitrate levels did not correlate with endotoxemia (r = -0.110). On the other hand, levels of orosomucoid, a protein synthesized by the liver in response to a stimulation by cytokines correlated with those of nitrate (respectively r = 0.343, p < 0.01). Hemoglobin levels were negatively correlated with serum nitrate levels (r = -0.328 p < 0.02). Cardiac index was higher in patients than in control subjects and paralleled the degree of liver failure (Child A/B/C vs control subjects: 3.60 +/- 0.25/ 4.10 +/- 0.19/4.47 +/- 0.25 vs 3.15 +/- 0.12 l.min.m2, p < 0.001). Cardiac index did not correlate with serum nitrate levels, urine nitrate excretion and endotoxemia.

Renal impairment accounts for the increased levels of serum nitrate in ascitic patients. A stimulation of nitric oxide production by cytokines may occur but endotoxemia is not involved in such a mechanism. Anemia has a role in nitric oxide activity. Nitric oxide generation assessed by nitrate in serum and urine does not seem to participate in the hyperdynamic circulatory syndrome in patients with cirrhosis.