ADMINISTRATION OF N-OMEGA-NITRO-L-ARGININE AMELIORATES PORTAL-SYSTEMIC SHUNTING IN PORTAL-HYPERTENSIVE RATS

Background: Nitric oxide, a vasodilator synthesized from l-arglnine by vascular endothelial cells, may play a role in the development of portal-systemic collaterals. This study investigated the effect of long-term inhibition of NO secretion on portal systemic shunting. Methods: Systemic and splanchnic hemodynamics and the degree of portal-systemic shunting were evaluated in partial portal vein-ligated rats after administration of placebo (0.9% saline) or Nω-nitro-l-arginine (NNA) (~2 μg · kg-1 · min-1) intravenously for 6 days. Results: NNA treatment induced increases in splanchnic arterial resistance (P < 0.001) and portal-collateral resistance (P < 0.05) and a decrease in portal venous inflow (P < 0.05). Portal pressure was not changed (NS). The splenic-systemic shunting was significantly decreased from 81% ± 5% in the placebotreated group to 69% ± 4% in the NNA-treated group (P < 0.05), paralleled by an insignificant reduction in the mesenteric-systemic shunting (64% ± 7% vs. 50% ± 6%, NS). The attenuation of portal-systemic shunting by NNA was further shown by an increase in the vascular resistance of portal-systemic collateral venous bed using an in situ portal-systemic collateral perfusion model (1.27 ± 0.05 vs. 1.07 ± 0.03 cm H2O · mL-1 · min-1; P < 0.001). Conclusions: The results show that in portal hypertensive rats, NNA reduces portal-systemic shunting without reducing portal pressure, suggesting that NO plays a role in the collaterallzation of the portal system. In addition, high flow through the portal-collateral bed is probably an important driving force that is independent of portal hypertension for the development of portal-systemic shunting in portal-hypertensive rats. © 1992.