Acute Effects of Nitric Oxide Synthase Inhibition on Systemic,Hepatic,and Renal Hemodynamics in Patients with Cirrhosis and Ascites

Abstract

Background

Nitric oxide synthase (NOS) inhibition has been demonstrated to correct systemic vasodilation and renal hypoperfusion in studies of patients with cirrhosis. In patients with decompensated cirrhosis, NOS blockade increases arterial pressure, but the acute effects on hepatic and renal hemodynamics are not known.

Methods

We examined the acute systemic, hepatic, and renal hemodynamic effects of N^G-monomethyl-l-arginine (l-NMMA) in 10 patients with decompensated cirrhosis. After baseline measurements, 3 mg/kg l-NMMA was administered as an IV bolus. At 20 minutes, if mean arterial pressure did not increase by at least 10 mm Hg above the baseline value, a second injection of 6 mg/kg was administered.

Results

In 5 of 10 patients, the second injection of l-NMMA 6mg/kg was necessary to achieve at least a 10 mm Hg increase in mean arterial pressure. Acute NOS inhibition increased systemic vascular resistance and decreased cardiac output, without causing changes in the hepatic venous pressure gradient. Hepatic blood flow decreased, but the indocyanine green intrinsic clearance and extraction remained unchanged. Plasma renin activity (from 9.5±2.9 to 6.7±1.6 ng/ml/h) and urinary prostaglandin E₂ (from 299±40 to 112±36 pg/ml) significantly decreased. No significant changes in glomerular filtration rate, renal plasma flow, and natriuresis occurred, however.

Conclusions

Acute l-NMMA infusion in patients with decompensated cirrhosis reduced hepatic blood flow and decreased plasma renin activity and urinary prostaglandin E₂, without causing significant changes in renal hemodynamics.