EFFECTS OF L-ARGININE ON THE SYSTEMIC, MESENTERIC, AND HEPATIC CIRCULATION IN PATIENTS WITH CIRRHOSIS

Nitric oxide (NO) is known to play an important role in modulating bot h the hepatic and mesenteric circulation under physiological and patho logical conditions. We investigated how L-arginine, a precursor of NO, modifies the hepatic and mesenteric circulation in patients with cirr hosis. The study design was a single-blind controlled study. We measur ed the systemic and portal hemodynamics before and following intraveno us L-arginine and saline infusion using pulsed Doppler ultrasonography in 20 patients with cirrhosis, and then the effects were compared wit h those found in 20 healthy subjects. In these patients, the effects o f L-arginine on hepatic circulation were investigated using hepatic ca theterization. L-Arginine infusion induced systemic vasodilation in bo th the healthy controls and the cirrhotic patients in a similar hemody namic manner. In these patients, the L-arginine-induced increase in th e portal flow was significantly higher than that of cardiac output (CO ); however, the relation was the inverse in healthy subjects. Moreover , the L-arginine-induced increase in the portal now was greater in the cirrhotic patients than that seen in healthy subjects. As a result, L -arginine infusion was thus found to selectively augment the hepatopet al portal blood flow in the cirrhotic liver. In patients, L-arginine i nfusion induced marked hepatic vasodilation as demonstrated by the red uced hepatic sinusoidal resistance (HSR) and increased estimated hepat ic blood flow (EHBF) associated with the ameliorated intrinsic clearan ce of indocyanine green. Despite the fall in HSR, the hepatic venous p ressure gradient (HVPG) increased following L-arginine infusion. The m esenteric and hepatic vascular areas of cirrhosis exhibited an increas ed susceptibility to the dilator action of L-arginine. These findings suggest that the enhanced NO production in the splanchnic vascular are a has an important role in the hepatic circulation in patients with ci rrhosis.