Administration of N omega-nitro-L-arginine ameliorates portal-systemic shunting in portal-hypertensive rats.
BACKGROUND
Nitric oxide, a vasodilator synthesized from L-arginine 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 N omega-nitro-L-arginine (NNA) (approximately 2 micrograms.kg-1 x 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 placebo-treated 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 x 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 collateralization 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.
Lee
F Y
FY
Hepatic Hemodynamic Laboratory, Veterans Affairs Medical Center, West Haven, Connecticut.
Colombato
L A
LA
Albillos
A
A
Groszmann
R J
RJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D006975:Hypertension, Portal / Q000503:physiopathology*; D008297:Male; D008643:Mesentery / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D019335:Nitroarginine; D010477:Perfusion; D011168:Portal System / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine