Article Text

Acute Effects of Nitric Oxide Synthase Inhibition on Systemic, Hepatic, and Renal Hemodynamics in Patients with Cirrhosis and Ascites
  1. Laurent Spahr,
  2. Pierre-Yves Martin,
  3. Emile Giostra,
  4. Michel Niederberger,
  5. Ursula Lang,
  6. Allessandro Capponi,
  7. Antoine Hadengue
  1. From the Divisions of Gastroenterology and Hepatology, Nephrology, Endocrinology and Diabetology, and the Department of Internal Medicine, University Hospital, Geneva, Switzerland.
  1. Address correspondence to: Laurent Spahr, MD, Division of Gastroenterology and Hepatology, University Hospital, 24 Rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland. Email: Laurent.Spahr{at}
  2. Presented in part at the annual meeting of the American Association for the Study of Liver Diseases (AASLD), November 5–7, 1999, Dallas, TX.


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.

Key Words
  • cirrhosis
  • hepatic blood flow
  • human study
  • indocyanine green
  • l-NMMA
  • nitric oxide
  • plasma renin activity
  • portal hypertension
  • prostaglandin E2
  • renal hemodynamics

Statistics from

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.