Nitric oxide synthase activity is increased in relation to the severity of liver dysfunction

1. Nitric oxide is a potent vasodilator which plays a major role in the control of blood pressure. The hyperdynamic circulation of cirrhosis has been linked to nitric oxide. 2. We measured neutrophil nitric oxide synthase activity in relation to the level of hepatic dysfunction in patients with liver disease of varying aetiology and severity. 3. Neutrophils were isolated from 21 patients (7 Child-Pugh score A, 6 grade B and 8 grade C) aged 28-76 (median 49) years. Nitric oxide synthase activity was measured using the conversion of oxyhaemoglobin to methaemoglobin by nitric oxide and expressed in terms of cell protein. Blood pressure and biochemical indices were recorded. Data were assessed using Kruskal-Wallis one-way analysis of variance, Mann-Whitney U-test or Pearson correlation as appropriate. 4. Systolic, mean arterial and diastolic blood pressures decreased with increasing hepatic damage (P = 0.031, P = 0.01 and P = 0.038 respectively). Nitric oxide synthase activity increased with the degree of liver dysfunction (P = 0.033) and was highest in patients with Child-Pugh score C. Systolic blood pressure correlated with nitric oxide synthase activity in patients with Child-Pugh score C (P = 0.029). 5. Our results show that nitric oxide synthase activity increases with increasing Child-Pugh score and is associated with the development of systemic hypotension. These data may support the involvement of nitric oxide in the haemodynamic disturbances seen in liver disease.