Effects of L-arginine on the systemic, mesenteric, and hepatic circulation of patients with cirrhosis

Abstract

Nitric oxide (NO) is known to play an important role in modulating both the hepatic and mesenteric circulation under physiological and pathological conditions. We investigated how L-arginine, a precursor of NO, modifies the hepatic and mesenteric circulation in patients with cirrhosis. The study design was a single-blind controlled study. We measured the systemic and portal hemodynamics before and following intravenous L-arginine and saline infusion using pulsed Doppler ultrasonography in 20 patients with cirrhosis, and then the effects were compared with those found in 20 healthy subjects. In these patients, the effects of L-arginine on hepatic circulation were investigated using hepatic catheterization. L-Arginine infusion induced systemic vasodilation in both the healthy controls and the cirrhotic patients in a similar hemodynamic manner. In these patients, the L-arginine-induced increase in the 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 flow 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 hepatopetal portal blood flow in the cirrhotic liver. In patients, L-arginine infusion induced marked hepatic vasodilation as demonstrated by the reduced hepatic sinusoidal resistance (HSR) and increased estimated hepatic blood flow (EHBF) associated with the ameliorated intrinsic clearance of indocyanine green. Despite the fall in HSR, the hepatic venous pressure gradient (HVPG) increased following L-arginine infusion. The mesenteric and hepatic vascular areas of cirrhosis exhibited an increased susceptibility to the dilator action of L-arginine. These findings suggest that the enhanced NO production in the splanchnic vascular area has an important role in the hepatic circulation in patients with cirrhosis. (HEPA-TOLOGY 1998;27:377-382.)Patients with cirrhosis exhibit circulatory abnormalities such as perturbation of the hepatic microcirculation, as well as systemic and mesenteric hyperemia. 1,2 It has recently been proposed that hepatic stellate cells play an important role in regulating hepatic sinusoidal tonus and the blood flow under physiological and pathological conditions. 3-7 The contractility of hepatic stellate cells depends on the dynamic control of the balance of two endothelium-derived vasoactive substances, endothelin 1 and nitric oxide (NO). [3][4][5][6][7] Endothelin produces sustained vasoconstriction in the liver, which appears to be related to the contraction of hepatic stellate cells. 3,4 In addition, NO is also a potent modulator of stellate cell contractility 5,6 and inhibits the vasoconstriction induced by endothelin in the perfused rat liver. 7 Therefore, both endothelin and NO play a critical role in modulating hepatic microcirculation.L-Arginine, a precursor of NO, induces systemic vasodilation and natriuresis when infused intravenously in humans. [8][9][10][...

Hepatic Blood Flow and Splanchnic Oxygen Consumption in Patients With Liver Failure. Effect of High–Volume Plasmapheresis

“…1,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] In these studies, ICG was used and the hepatic extraction was measured and taken into account in the calculations. The median (of the reported mean HBF in the individual studies) was 1.18 L/min (range 0.93-1.90).…”

The paradox of nitric oxide in cirrhosis and portal hypertension: Too much, not enough

“…35,75 Moreover, invitro perfusion of cirrhotic livers with L-arginine reduces microcirculatory hyperreactivity to norepinephrine. 76 Whereas systemic application of L-arginine to patients with cirrhosis induces marked hepatic vasodilation, 77 the mechanism of these effects is not clear; perhaps reduced bioavailability of tetrahydrobiopterin (BH 4 ) leads to a "paradoxical" deficiency of L-arginine. It is assumed that there is cooperation between BH 4 and L-arginine binding sites on NOS, thereby reducing the Kd for each other.…”

Effects of sympathetic nerves and angiotensin II on renal sodium and water handling in rats with common bile duct ligature

“…liver cirrhosis; nitric oxide; excretion SODIUM AND VOLUME RETENTION is a common problem in patients with liver cirrhosis (33, 34). Neurohumoral vasoconstrictors but also the production of a vasodilator like nitric oxide are considerably activated (16,21,22,27,29,31,42).Inhibition of the sympathetic nervous system (1, 35) or angiotensin II in patients (30, 38) or animal models (10,14,20) could improve sodium and water excretion transiently, although possible decreases in blood pressure or renal perfusion could eventually worsen volume homeostasis instead of improving it (1, 8, 9). …”

“…liver cirrhosis; nitric oxide; excretion SODIUM AND VOLUME RETENTION is a common problem in patients with liver cirrhosis (33,34). Neurohumoral vasoconstrictors but also the production of a vasodilator like nitric oxide are considerably activated (16,21,22,27,29,31,42).…”